Association between Pesticide Exposure and Colorectal Cancer Risk and Incidence: A Systematic Review

Eryn K Matich; Jonathan A Laryea; Kathryn A Seely; Shelbie Stahr; L Joseph Su; Ping-Ching Hsu

doi:10.1016/j.ecoenv.2021.112327

. Author manuscript; available in PMC: 2022 Aug 1.

Published in final edited form as: Ecotoxicol Environ Saf. 2021 May 21;219:112327. doi: 10.1016/j.ecoenv.2021.112327

Association between Pesticide Exposure and Colorectal Cancer Risk and Incidence: A Systematic Review

Eryn K Matich ¹, Jonathan A Laryea ², Kathryn A Seely ³, Shelbie Stahr ⁴, L Joseph Su ^4,^*, Ping-Ching Hsu ^1,^*

PMCID: PMC8694176 NIHMSID: NIHMS1707110 PMID: 34029839

Abstract

Background

Studies investigating the association between pesticide exposure and colorectal cancer (CRC) risk have been inconclusive.

Objectives

Investigate the association between pesticide exposure and CRC risk through a systematic literature review.

Methods

CRC has the fourth-highest rate of cancer-caused death in the US after lung cancer, breast cancer in women, and prostate cancer in men. Here we have conducted a systematic literature search on studies examining the association between any pesticide exposure and CRC risk using PubMed, MEDLINE via EBSCO host, and Embase according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.

Results

Following the review, 139 articles were included for qualitative evaluation. Study participants were farmers, pesticide applicators, pesticide manufacturers, spouses of pesticide applicators, farm residents, Korean veterans of the Vietnam War, rural communities, and those who consumed food with pesticide residues. The studies’ results were split between those with significant positive (39 significant results) and inverse (41 significant results) associations when comparing pesticide exposure and CRC risk.

Discussion

From our literature review, we have identified a similar number of significant positive and inverse associations of pesticide exposure with CRC risk and therefore cannot conclude whether pesticide exposure has a positive or inverse association with CRC risk overall. However, certain pesticides such as terbufos, dicamba, trifluralin, S-ethyl dipropylthiocarbamate (EPTC), imazethapyr, chlorpyrifos, carbaryl, pendimethalin, and acetochlor are of great concern not only for their associated elevated risk of CRC, but also for the current legal usage in the United States (US). Aldicarb and dieldrin are of moderate concern for the positive associations with CRC risk, and also for the illegal usage or the detection on imported food products even though they have been banned in the US. Pesticides can linger in the soil, water, and air for weeks to years and, therefore, can lead to exposure to farmers, manufacturing workers, and those living in rural communities near these farms and factories. Approximately 60 million people in the US live in rural areas and all of the CRC mortality hotspots are within the rural communities. The CRC mortality rate is still increasing in the rural regions despite the overall decreasing of incidence and mortality of CRC elsewhere. Therefore, the results from this study on the relationship between pesticide exposure and CRC risk will help us to understand CRC health disparities.

Keywords: colorectal cancer, pesticides, environmental exposure, occupational exposure

1. Introduction

Cancer is the second leading cause of death in the United States (US) following heart disease (ACS, 2019), and colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the US (ACS, 2019). Like many other cancer types, there are some genetic mutations associated with CRC. However, more than half (55%) of CRC in the US are attributable to modifiable risk factors such as diet, lifestyle factors, and co-morbidities that can promote intestinal inflammation and facilitate polyp growth (ACS, 2019). Some of these include heavy alcohol consumption (average of greater than three drinks a day) (McNabb et al., 2020), smoking (Carter et al., 2015), red and processed meat consumption (Vieira et al., 2017), physical inactivity (Boyle et al., 2012), obesity (Xue et al., 2017), and type 2 diabetes (Ma et al., 2018). These lifestyle choices and co-morbidities are highly correlated with socioeconomic status. Additionally, education level, occupation, and income affecting living environment and access to resources also contribute to cancer risk (ACS, 2021).

One factor that has been studied and shown to be correlated to CRC risk, in some cases, is exposure to substances that are meant to control pests. In this review, these substances will be referred to as pesticides, but this definition also includes other pest repellent substances such as herbicides, insecticides, fungicides, and many others (EPA, 2020). Pesticide exposure can result from a related occupation such as farming (Ilgaz and Gozum, 2018; Salerno et al., 2016; Settimi et al., 2001), pesticide application (Alexander et al., 2012; Cantor and Silberman, 1999; Greenburg et al., 2008; Hou et al., 2006; Lee et al., 2004b; Lynch et al., 2006; Rusiecki et al., 2006), and pesticide manufacturing (Acquavella et al., 1996; Leet et al., 1996; Wilkinson et al., 1997). Additionally, spouses of farmers (Deziel et al., 2019), those living in rural areas (Wang et al., 2002), those who eat non-organic foods (Baudry et al., 2018; Callahan et al., 2017), or those who apply or have pesticides applied to their yards can also be exposed (Su et al., 2016).

Pesticides that are applied to farms or yards can remain in the environment for longer than intended. Sometimes pesticides either sit on top of the soil (surface soil) and therefore spread via dust, runoff, or leach through the soil (parent soil) and thus reach the groundwater and, in some cases, drinking water (Sjerps et al., 2019; Sultana et al., 2018; Xu et al., 2018). Some studies have found pesticides, such as neonicotinoids, remain in the dust and soil at least one year following the previous planting season. These pesticides were an order of magnitude higher in concentration on the surface soil than the parent soil (Limay-Rios et al., 2016). Another pesticide, fipronil, is a phenylpyrazole insecticide that disrupts the insect’s central nervous system by blocking chloride channels. Similar to the neonicotinoids, it was found that degradation products of fipronil were three to nine times higher in dust than in soil and therefore were also detected in runoff samples (Cryder et al., 2019). Another study has found that pesticides such as 2-methyl-4-chlorophenoxyacetic acid (MCPA) leach more from frozen vs. unfrozen topsoil (Holten et al., 2018).

Most of the scientific articles identified have analyzed the association between pesticide exposure and colon cancer, rectal cancer, or CRC risk using epidemiological methods as compared to studies that measured the level or concentration of pesticides in the biological samples. Epidemiological methods have limitations mainly because they rely on self-reporting, whereas biological sample measurement studies analyze specific or multiple pesticide metabolites in human samples. Samples from stool, colon wash, colon tissue, or polyps are optimal to study the association with colon or rectal cancer risk. In this review, we were only able to identify biological sample measurement studies that measured pesticide levels in serum samples.

Several review papers have previously looked into the associations between pesticide exposure and cancer risk (Acquavella et al., 1998; Alavanja and Bonner, 2012; Alexander et al., 2012; Blair and Freeman, 2009; Blair et al., 1985a; Blair et al., 1992; Burns, 2005; Oddone et al., 2014; Weichenthal et al., 2010), but only two specifically focused on CRC only and no other cancers (Alexander et al., 2012; Oddone et al., 2014) while the others looked at cancer more broadly or various types of cancer (Acquavella et al., 1998; Alavanja and Bonner, 2012; Blair and Freeman, 2009; Blair et al., 1985a; Blair et al., 1992; Burns, 2005; Weichenthal et al., 2012). In addition, only one third (three out of nine) of the review papers looked at the association between certain pesticide exposures and cancer risks including CRC risk (Alavanja and Bonner, 2012; Alexander et al., 2012; Weichenthal et al., 2010) while the rest more generally looked at pesticide exposure among different occupations or environmental risk factors (farmers, pesticide applicators, agricultural populations, and crop and animal production) and the association with cancer risk including CRC instead of the effect of specific pesticide exposure or the effect of specific pesticide exposure on the risk of other cancer types (Acquavella et al., 1998; Alexander et al., 2012; Blair and Freeman, 2009; Blair et al., 1985a; Burns, 2005; Oddone et al., 2014). The three review papers that looked at the association between certain pesticide exposure and CRC risk (Alavanja and Bonner, 2012; Alexander et al., 2012; Weichenthal et al., 2010) found six pesticides including aldicarb (Lee et al., 2007b), dicamba (Samanic et al., 2006), S-ethyl dipropylthiocarbamate; EPTC (van Bemmel et al., 2008), imazethapyr (Koutros et al., 2009), trifluralin (Kang et al., 2008), and fonofos (Lee et al., 2007b) with significant positive associations with colon cancer risk, five pesticides including chlordane (Purdue et al., 2007), chlorpyrifos (Lee et al., 2004a; Lee et al., 2007b), pendimethalin (Hou et al., 2006), toxaphene (Lee et al., 2007b), and carbaryl (Lee et al., 2007b) with significant positive associations with rectal cancer risk, and only one pesticide, 2,4-dichlorophenoxyacetic acid; 2,4-D, with a significant inverse association with colon cancer risk (Lee et al., 2007b). The remaining review papers that more generally looked at the association between occupational or environmental exposure to pesticides and CRC risk found that farmers, crop and animal production, and agricultural populations showed mostly significant inverse associations with colon cancer, rectal cancer, or CRC risk (Acquavella et al., 1998; Alexander et al., 2012; Blair and Freeman, 2009; Blair et al., 1985a; Oddone et al., 2014).

There have also been some research studies that suggest some pesticides, such as Metarhizium anisopliae (Dornetshuber-Fleiss et al., 2013), deguelin (Murillo et al., 2003; Murillo et al., 2002), oryzalin (Powis et al., 1997), benzimidazole carbamates (Wales et al., 2015), rotenone (Yoshitani et al., 2001), and thujone (Zhou et al., 2016) are anti-carcinogenic. Additionally, studies have shown a lower incidence of CRC in farmers compared to the general population (Garabrant et al., 1984). This has been attributed to factors such as lower smoking rates and higher physical activity (Garabrant et al., 1984).

Below we discussed groups of pesticides and individual pesticides that have been shown to have significant associations with colon cancer, rectal cancer, or CRC risk. We have discussed the results of previous studies showing the persistence of these pesticides in the environment and in organisms, including humans, as well as some of the reported health issues associated with exposure to these pesticides.

Insecticides are pesticides that have various methods of action to kill insects considered to be pests. Organochlorine insecticides (OCIs) have been used globally and across the US and many have been shown to be persistent in the environment and in organisms. Some examples of OCIs include dichlorodiphenyltrichloroethane (DDT), heptachlor, lindane, chlordane, and toxaphene. DDT opens sodium channels in neurons, causing the sodium channels to spontaneously fire and subsequently leads to spasms and death (Dong, 2007). Lindane is an insecticidal neurotoxin that interferes with gamma-aminobutyric acid (Hall and Hall, 1999; Narahashi, 2002; Sunol et al., 1989). Chlordane is environmentally resistant to degradation and bioaccumulates and is toxic to humans and the environment (EPA, 1994). Heptachlor persists in the environment for many years and can be detected in human blood, fat, and tissue when exposed (CDC, 1993). Toxaphene remains in the soil for 1 to 14 years without degrading (EPA, 1996). Another group of insecticides are organophosphate insecticides (OPIs) and some such as tebufos have been shown to be associated with various cancers (Lerro et al., 2015a). Carbamate insecticides reversibly inhibit acetylcholinesterase, and therefore affect the nervous system leading to neurotoxic effects (Fukuto, 1990). Three examples of carbamate insecticides are butylate, carbaryl, and aldicarb. Butylate is used specifically for corn crops and along with carbaryl is not believed to cause cancer in humans (EPA, 1993; HSDB, 1993), while aldicarb is believed to be linked to cancer (EPA, 2002).

Another type of pesticide which is used to kill plants such as weeds that are considered harmful to the agricultural product of interest are called herbicides. Some chlorophenoxy herbicides such as 2,4-D and MCPA are growth regulators (Grossmann, 2010) and degrade in soil (Helweg, 1987; NPIC, 2008) but they have been shown to cause health problems in humans. Some of these health problems include severe eye irritations (EPA, 2004, 2005) and 2,4-D has been shown to potentially cause fertility problems in men (Tan et al., 2016), and the World Health Organization (WHO) has classified 2,4-D as a possible carcinogen (WHO, 2020). Another chlorophenoxy herbicide is dicamba which functions by causing weeds to grow beyond their nutrient supply and can become airborne and cause damage to nearby fields (Bunch et al., 2012). Anilide/ aniline herbicides are another group of herbicides and some examples include acetochlor, alachlor, pendimethalin, and trifluralin. Trifluralin interrupts mitosis to prevent root development (Senseman, 2007) and is toxic to aquatic life (Harrahy, 2003b). Pendimethalin inhibits cell elongation and division (EPA, 2007) and can increase the risk of developing pancreatic cancer (Andreotti et al., 2009). Additionally, acetochlor and alachlor are also herbicides that inhibit cell elongation. Acetochlor has effects on aquatic life (Harrahy, 2003a) and is classified as a probable human carcinogen (WHO, 2020). Alachlor causes slight eye and skin irritation (EPA, 1998) and has been detected in drinking water (Barbosa et al., 2016). EPTC is a thiocarbamate herbicide that inhibits the formation of cuticles in the early growth of seedlings and can cause neurotoxic effects such as neuronal degradation or necrosis in rats and dogs (EPA, 1999).

We have included colon cancer, rectal cancer, and CRC in this literature review and separated the discussions because some articles analyzed colon and rectal cancer separately while others grouped them together in what is commonly called colorectal cancer (CRC). This review included 139 research articles analyzing 56 different pesticides.

We will also discuss the bans, use, detection on imported food, and hazards of these 56 pesticides reviewed, which are summarized in Table 1. Ten of these 56 pesticides have not been banned anywhere, as reported by the Pesticide Action Network International (PAN) (PAN, 2020) and by Donley et al. 2019 (Donley, 2019). Five of these ten pesticides that are not banned anywhere (Donley, 2019; PAN, 2020) are classified as hazardous by WHO (WHO, 2019) including dicamba, glyphosate, metolachlor, metribuzin, and ziram. Of these 56 pesticides, 31 have been banned by the European Union (EU) and United Kingdom (UK) along with other countries (Donley, 2019; PAN, 2020), 23 of which have been classified as hazardous by WHO (WHO, 2019). Of these 56 pesticides, 17 have been banned or not approved in the US (Donley, 2019; PAN, 2020), 12 of which are classified as hazardous by WHO (WHO, 2019). In addition, 23 out of these 56 pesticides have been detected on imported food by the U. S. Food and Drug Administration (FDA) as of 2018 (FDA, 2018), including 4 which have been banned in the US (Donley, 2019; PAN, 2020) and 18 that the WHO have reported as slightly to extremely hazardous (WHO, 2019).

Table 1.

Pesticide Bans by Country, Hazards, Use, and Detection in Imported Foods.

Pesticide	Hazard rating (WHO)¹	Number of countries banned (PAN)², Donley 2019³	Used in USA as of 2017 (USGS)⁴	Detected on imported foods as of 2018 (FDA)⁵
2,4-D	moderately hazardous	3 (Mozambique, Norway, Vietnam)	x	x
2,4,5-T		1 US
2,4,5-TP		0
acetochlor	slightly hazardous	38 (EU 27, UK + 10 others)	x
alachlor	moderately hazardous	95 (US, EU 27, UK + 66 others)	x
aldicarb	extremely hazardous	104 (US, EU 27, UK + 75 others)	x
aldrin		1 US
aluminium phosphide		1 (China)
atrazine	slightly hazardous	37 (EU 27, UK + 9 others)	x	x
benomyl		35 (US, EU 27, UK + 6 others)
butylate	Slightly hazardous	30 (US, EU 27, UK, Brazil)
captan		6 (Cambodia, Fiji, Guinea, Oman, Saudi Arabia, Vietnam)	x	x
carbaryl	moderately hazardous	35 (EU 27, UK + 7 others)	x	x
carbofuran	highly hazardous	64 (US, EU 27, UK + 35 others)		x
carbon disulfide		0
carbon tetrachloride		31 (EU 27, UK, Brazil, Switzerland, Thailand)
chlordane	moderately hazardous	142 (US, EU 27, UK + 113 others)		x
chlorimuronethyl		0
chlorothalonil		3 (Colombia, Palestine, Saudi Arabia)	x	x
chlorpyrifos	moderately hazardous	4 (Palestine, Saudi Arabia, Sri Lanka, Vietnam)	x	x
coumaphos	highly hazardous	30 (EU 27, UK, Cambodia, China)		x
cyanazine	moderately hazardous	30 (US, EU 27, UK, Oman)
DDT	moderately hazardous	136 (US, EU 27, UK + 107 others)		x
diazinon	moderately hazardous	32 (EU 27, UK, Argentina, India, Mozambique, Palestine)	x	x
dicamba	moderately hazardous	0	x
dichlorvos	highly hazardous	33 (EU 27, UK + 5 others)		x
dieldrin		1 US		x
EPTC	moderately hazardous	29 (EU 27, UK, Brazil)	x
ethylene dibromide		124 (EU 27, UK + 96 others)
fonofos		34 (US, EU 27, UK + 5 others)
glyphosate	slightly hazardous	0	x	x
heptachlor		1 US
hexachloro benzene	extremely hazardous	129 (US, EU 27, UK + 100 others)
imazethapyr		29 (EU 27, UK, Norway)	x	x
lindane	moderately hazardous	121 (US, EU 27, UK + 92 others)
malathion	slightly hazardous	2 (Palestine, Syria)	x	x
mancozeb		1 (Saudi Arabia)	x
maneb		30 (US, EU 27, UK, Brazil)
MCPA	moderately hazardous	2 (Cambodia, Thailand)	x
metalaxyl	moderately hazardous	1 (Brazil)	x	x
methyl bromide		35 (EU 27, UK + 7 others)
metolachlor	slightly hazardous	0	x	x
metribuzin	moderately hazardous	0	x	x
paraquat	moderately hazardous	46 (EU 27, UK + 18 others)	x
parathion (ethyl)	extremely hazardous	114 (US, EU 27, UK + 85 others)
pendimethalin	moderately hazardous	1 (Norway)	x	x
pentachloro phenol	highly hazardous	114 (US, EU 27, UK + 85 others)
permethrin	moderately hazardous	29 (EU 27, UK, Syria)	x	x
petroleum oil		0	x
phorate	extremely hazardous	38 (EU 27, UK + 10 others)	x	x
terbufos	extremely hazardous	34 (EU 27, UK + 6 others)	x
tetrachloro phenol		0
toxaphene		1 US
trichlorfon	moderately hazardous	53 (US, EU 27, UK + 24 others)
trifluralin		28 (EU 27, UK)	x	x
ziram	moderately hazardous	0	x

Open in a new tab

World Health Organization (WHO) Recommended Classification of Pesticides by Hazard and Guidelines to Classification 2019 (WHO, 2019),

Pesticide Action Network (PAN) International Consolidated List of Banned Pesticides, October 20, 2020 (PAN, 2020),

Donley 2019 (Donley, 2019),

⁴

United States Geological Survey (USGS) Pesticide National Synthesis Project, Estimated Annual Agricultural Pesticide Use, Archived preliminary county level pesticide use estimates, 2017 (USGS, 2017),

⁵

U.S. Food and Drug Administration (FDA) Pesticide Residue Monitoring Program Fiscal Year 2018 Pesticide Report (FDA, 2018).

The relationship between pesticide exposure and CRC risk is of particular interest to understand CRC health disparities. Therefore, this systematic review aimed to investigate the association between human pesticide exposure and CRC risk and incidence. We hypothesized that those exposed to pesticides would have a higher risk and incidence of CRC.

2. Methods

2.1. Literature Search

This systematic, qualitative review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and flow diagram (Moher et al., 2009). We systematically searched PubMed, MEDLINE via EBSCO host, and Embase for research articles that examined the association between human pesticide exposure and colon cancer, rectal cancer, or CRC risk and incidence. We used the terms colon cancer, rectal cancer, and CRC because different articles specifically examined colon and rectal cancer separately, while others grouped the two into colorectal cancer (CRC). We used the term pesticide broadly to include pesticides, herbicides, insecticides, and other pest deterrents such as fumigants. We performed a broad literature search and did not restrict our search any further based on certain pesticides, insecticides, herbicides, or groups. The bibliographic search was performed in February 2020 and encompassed the available literature up to that time. The following search terms were used: (colorectal OR colon) AND cancer AND (pesticide OR herbicide OR insecticide). An English language filter was applied because of the lack of translation resources. All original articles found on the topic were epidemiological studies or biological sample measurement studies, and only those involving humans were included. All cell culture and animal studies were excluded. Figure 1 is a flow diagram illustrating this literature review process. Odds ratio (OR), relative risk/risk ratio (RR), hazard ratio (HR), standardized incidence ratio (SIR), standardized mortality ratio (SMR), standardized risk ratio (SRR), proportionate mortality ratio (PMR), proportionate cancer mortality ratio (PCMR), mortality odds ratio (MOR), confidence interval (CI), p-trend, and p-value were primary endpoints for the epidemiological studies and mean abundance/ level/ concentration and p-value were primary endpoints for the biological sample measurement studies. We did not calculate these primary endpoints; they were calculated in these primary studies that we are reviewing. Epidemiological effect sizes report a number, which denotes the strength of the association of the specific exposure on the outcome, which in this case is the association of the pesticide exposure on the CRC risk. Explained more simply, a positive association can mean that an increased level of the exposure (or presence of an exposure vs. no exposure) has resulted in an increased risk of the outcome. Our intention is to determine if there is an overall association between pesticide exposure and colon cancer, rectal cancer, and CRC risk, discuss this association, and discuss which certain pesticides or pesticide groups seem to be of most concern.

Figure 1. — Preferred Reporting for Systematic Review and Meta-Analyses Flow Diagram Modified from the PRISMA Group Source.

2.2. Eligibility Criteria

For this systematic analysis, the eligibility criteria included human epidemiology or human biological sample measurement studies researching the association (effect size, confidence interval, p-trend, and p-value or abundance and p-value) between pesticide exposure and colon cancer, rectal cancer, or CRC risk, incidence, or mortality. We were primarily focused on comparing the risk associated with occupations such as farming, pesticide application, and manufacturing. The abstracts were manually screened for relevance.

2.3. Data Collection Process

The data collection process was performed manually, and for studies that were deemed relevant, we saved the citation information, abstract, and article in a portable document format (PDF). For epidemiological studies, the data of interest were overall conclusions of association, correlation or statistical significance, OR, RR, HR, SIR, SMR, SRR, PMR, PCMR, MOR, 95% CI, and/or p-values/p-trends, and for biological sample measurement studies, the data of interest were abundance/ level/ concentration and p-value. Significant results were defined as those with a p-value or p-trend less than 0.05 or an effect size greater than or less than 1 with a confidence interval that does not include 1. For biological sample measurement studies the mean abundances/ levels/ concentrations were divided (cancer/ control) to determine the fold change. Study results were then described as positively (effect size or fold change greater than 1) or inversely associated (effect size or fold change less than 1) and significant depending on the confidence interval, p-value or p-trend. For our purposes, we will group the level of positive or inverse association for the epidemiological studies calculated from 1–10% disease rate of the non-exposed group for Cohen’s d of 0.2 as small, 0.5 as medium, and 0.8 as large associations (Cohen, 1988). Based on Cohen et al., we defined the effect sizes of the epidemiological studies as small positive associations ranging from 1.01–1.68, medium positive associations 1.69–3.50, and large positive associations 3.51 and up, whereas small inverse associations ranging from 0.99–0.59, medium inverse associations 0.58–0.28, and large inverse associations 0.27–0.01. Study results were then ranked into levels of concern based on the resulting association, statistical significance, and pesticide use and detection in the US. Pesticide results showing low concern involve pesticides already banned in the US or those that show inverse or no association with colon cancer, rectal cancer or CRC risk. Pesticides of moderate concern show (1) positive association with these types of cancers, are considered banned in the US but have been shown to be used as recently as 2017 or are still detectable in imported produce as of 2018; (2) pesticides in which studies have reported inconsistent results (positive in one study and inverse in another); or (3) pesticides shown to have small positive associations with these types of cancer that have not been banned in the US. Finally, pesticides of high concern are those that have been reported to have medium or large positive associations with these types of cancers and that have not been banned in the US.

3. Results and Discussion

3.1. Study Selection, Population, and Characteristics

Overall, we identified 139 studies for qualitative analysis (Table 2–6 and Figure 1). The systematic review was comprised of studies of farmers, pesticide applicators, pesticide manufacturing workers, pest-control workers, spouses of farmers, farm residents, rural populations, Korean Veterans who fought in the Vietnam war, people who ate food that may contain pesticide residues, and controls. Not all studies separated the participants by specialty; therefore, the term farmer is used more broadly. The studies were from 21 countries, including the US, Brazil, Egypt, Korea, Italy, Turkey, Spain, France, Iceland, Israel, Denmark, Germany, New Zealand, the UK, the Netherlands, Canada, Australia, Costa Rica, Sweden, Finland, and Iran. The publication dates of these studies included spanned 70 years (ranging from 1949 to 2019).

Table 2.

Associations Between Pesticide Exposure and Colon Cancer Risk.

Type	Group	Pesticide	Effect size summary	Reference
Insecticides	Organochlorine	Chlordane	RR 1.42 (0.87–2.32)^*	Louis et al. 2017(Louis et al., 2017)
		Chlordane	OR 0.7 (0.5–1.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Heptachlor	RR 1.24 (0.46–3.36)^*	Louis et al. 2017(Louis et al., 2017)
		Heptachlor	OR 0.8 (0.5–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Aldrin	RR 1.73 (0.76–3.91)^*	Louis et al. 2017(Louis et al., 2017)
			IWLED RR 0.4 (0.2–1.0) p-trend 0.04^{^}	Purdue et al. 2007(Purdue et al., 2007)
			OR 0.6 (0.4–1.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Dieldrin	RR 2.41 (0.89–6.53)^*	Louis et al. 2017(Louis et al., 2017)
		Dieldrin	OR 0.7 (0.4–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Aldrin and Dieldrin	SMR 1.40 (0.38–3.57)^*^{^}	van Amelsvoort et al. 2009(van Amelsvoort et al., 2009)
		Toxaphene	RR 1.31 (0.42–4.12)^*	Louis et al. 2017(Louis et al., 2017)
		Toxaphene	OR 1.1 (0.7–1.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Pentachlorophenol and Tetrachlorophenol	SMR 1.00 (0.83–1.18), SIR 0.94 (0.81–1.09)^*	Demers et al. 2006(Demers et al., 2006)
		DDT	PMR 0.23 (0.03–0.84)^*^{^}	Cocco et al. 1997(Cocco et al., 1997)
			RR 1.17 (0.70–1.95)^*	Louis et al. 2017(Louis et al., 2017)
			OR 0.9 (0.6–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Lindane (gamma HCH)	RR 0.79 (0.25–2.49)^*	Louis et al. 2017(Louis et al., 2017)
			male SIR 0.58 (0.47–0.70), female SIR 0.84 (0.36–1.65)^*	Rafnsson 2006(Rafnsson, 2006)
			OR 0.7 (0.4–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Carbon tetrachloride/carbon disulfide	OR 0.8 (0.4–1.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organophosphate	Trichlorfon	OR 1.5 (0.4–6.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Dichlorovos	RR 1.48 (0.78–2.80) p-trend 0.25	Koutros et al. 2008(Koutros et al., 2008)
		Dichlorovos	OR 1.5 (0.9–2.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Chlorpyrifos	RR 0.72 (0.48–1.07)^*	Lee et al. 2004a(Lee et al., 2004a)
		Chlorpyrifos	OR 0.8 (0.5–1.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Terbufos	T1 vs. T3 HR 1.77 (1.01–3.01) p-trend 0.009	Bonner et al. 2010(Bonner et al., 2010)
		Terbufos	OR 0.9 (0.6–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Fonofos	RR 1.66 (0.92–3.03) p-trend 0.14	Mahajan et al. 2006(Mahajan et al., 2006a)
		Fonofos	0 vs. T3 OR 2.4 (1.2–4.8) p trend 0.105, OR 1.5 (1.0–2.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Malathion	OR 0.8 (0.5–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Parathion	OR 0.9 (0.6–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Phorate	0 vs. T4 RR 1.07 (0.49–2.52) p-trend 0.74, T1 vs. T4 RR 2.48 (0.84–7.36) p-trend 0.18	Mahajan et al. 2006(Mahajan et al., 2006b)
		Phorate	OR 1.2 (0.8–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Coumaphos	OR 1.0 (0.6–1.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Diazinion	OR 0.7 (0.5–1.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Carbamate	Aldicarb	0 vs. T2 OR 5.2 (1.5–18.1) p trend 0.008, OR 2.1 (1.3–3.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Carbofuran	RR 1.34 (0.54–3.31) p-trend 0.68	Bonner et al. 2005(Bonner et al., 2005)
		Carbofuran	OR 1.0 (0.7–1.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Carbaryl	RR 0.80 (0.30–2.14) p-trend 0.62	Mahajan et al. 2007(Mahajan et al., 2007)
		Carbaryl	OR 0.9 (0.6–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Butylate	IWLED RR 0.35 (0.13–0.94) p-value<0.05 p-trend 0.04	Lynch et al. 2009(Lynch et al., 2009)
		Butylate	OR 0.9 (0.7–1.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Maneb/mancozeb	OR 0.7 (0.4–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Ziram	OR 0.7 (0.2–2.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Pyrethroid	Permethrin	LED RR 1.32 (0.75–2.34) p-trend 0.91	Rusiecki et al. 2009(Rusiecki et al., 2009)
	Pyrethroid	Permethrin	crops OR 0.9 (0.5–1.5), livestock OR 1.4 (0.9–2.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organobromine	Ethylene dibromide	OR 0.6 (0.2–1.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Other	Petroleum oil	OR 0.9 (0.7–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
Herbicides	Chlorophenoxy	2,4,5-TP	OR 0.6 (0.3–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		2,4,5-T	OR 0.8 (0.6–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		2,4-D	SIR 0.95 (0.55–1.55)^*	Burns et al. 2011(Burns et al., 2011)
		2,4-D	0 vs. T3 OR 0.4 (0.2–0.8) p trend 0.011^{^}, OR 0.6 (0.4–0.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		2,4-D and MCPA	white men SRR 0.98 (0.88–1.09)^, white women SRR 0.99 (0.88–1.12)^	Schreinemachers 2000(Schreinemachers, 2000)
		Dicamba	LED T1 vs. T4 RR 3.29 (1.40–7.73) p-trend 0.02	Samanic et al. 2006(Samanic et al., 2006)
		Dicamba	OR 0.9 (0.6–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Anilides/ anilines	Acetochlor	RR 1.07 (0.66–1.73) p>0.05, IWLED RR 1.67 (0.90–3.11) p-trend 0.20	Lerro et al. 2015(Lerro et al., 2015b)
		Alachlor	SIR 2.56 (0.31–9.25)^*^{^}	Acquavella et al. 2004(Acquavella et al., 2004)
			SIR 0.76 (0.58–0.98)^*, LED RR 0.62 (0.20–1.99) p-trend 0.53, IWLED RR 1.14 (0.40–3.23) p-trend 0.64	Lee et al. 2004b(Lee et al., 2004b)
			OR 0.8 (0.6–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Metolachlor	LED RR 1.30 (0.55–3.08) p-trend 0.32	Rusiecki et al. 2006(Rusiecki et al., 2006)
		Metolachlor	OR 1.0 (0.7–1.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Pendimethalin	RR 0.4 (0.05–3.2)^{^} p-trend 0.20	Hou et al. 2006(Hou et al., 2006)
		Pendimethalin	OR 1.2 (0.8–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Trifluralin	IWLED RR 1.76 (1.05–2.95) p-trend 0.036	Kang et al. 2008(Kang et al., 2008)
		Trifluralin	OR 1.0 (0.7–1.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Trazines	Atrazine	RR 1.26 (0.88–1.80) p-trend 0.04	Beane Freeman et al. 2011(Beane Freeman et al., 2011)
			LED RR 0.88 (0.41–1.89) p-trend 0.98	Rusiecki et al. 2004(Rusiecki et al., 2004)
			OR 0.8 (0.6–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Cyanizine	IWLED RR 0.57 (0.27–1.17) p-trend 0.21	Lynch et al. 2006(Lynch et al., 2006)
		Cyanizine	OR 0.8 (0.6–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Metribuzin	OR 0.8 (0.6–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Metribuzin	LED 0 vs. T3 RR 2.07 (0.94–4.60) p-trend 0.06, IWLED 0 vs. T3 RR 1.69 (0.69–4.10) p trend 0.22	Delancey et al. 2009(Delancey et al., 2009)
	Thiocarbamate	EPTC	LED RR 2.09 (1.26–3.47) p-trend <0.01	van Bemmel et al. 2008(van Bemmel et al., 2008)
	Thiocarbamate	EPTC	OR 1.2 (0.8–1.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Pyridine	Imazethapyr	RR 1.78 (1.08–2.93) p-trend 0.02, proximal colon RR 2.73 (1.42–5.25) p-trend 0.001, distal colon RR 1.21 (0.55–2.68) p-trend 0.75	Koutros et al. 2009(Koutros et al., 2009)
	Pyridine	Imazethapyr	1.2 (0.8–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Sulfonylurea	Chlorimuron ethyl	OR 0.8 (0.5–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organophosphate	Glyphosate	LED RR 0.9 (0.4–1.7) p-trend 0.54, IWLED RR 1.4 (0.8–2.5) p-trend 0.10^{^}	De Roos et al. 2005(De Roos et al., 2005)
	Organophosphate	Glyphosate	OR 1.0 (0.7–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Dipyridylium	Paraquat	OR 0.7 (0.5–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Dipyridylium	Paraquat	RR 0.89 (0.63–1.25) ^*	Park et al. 2009(Park et al., 2009)
Fungicides	Benimazole	Benomyl	OR 0.7 (0.4–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Phthalimide	Captan	0 vs. T3 RR 0.90 (0.37–2.20) p-trend 0.44, T1 vs. T3 RR 0.58 (0.16–2.17) p-trend 0.23	Greenburg et al. 2008(Greenburg et al., 2008)
	Phthalimide	Captan	OR 0.7 (0.4–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organochlorine	Chlorothalonil	RR 1.46 (0.70–3.03) p-trend 0.31	Mozzachio et al. 2008(Mozzachio et al., 2008)
	Organochlorine	Chlorothalonil	OR 1.4 (0.9–2.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Acylalanine	Metalaxyl	OR 1.1 (0.7–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
Fumigants	Other	Aluminum phosphide	OR 0.7 (0.3–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Methyl bromide	IWLED RR 0.81 (0.37–1.79) p-trend 0.77	Barry et al. 2012(Barry et al., 2012)
		Methyl bromide	OR 1.3 (0.9–2.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)

Open in a new tab

Results that were statistically significant were bolded under the effect size summary.

No p-value listed in the publication.

^{^}

Only one or no decimal points reported in the original publication. Lifetime exposure days (LED), Intensity weighted lifetime exposure days (IWLED), Tertile 1 (T1), Tertile 2 (T2), Tertile 3 (T3), Tertile 3 lower (T3L), Tertile 3 upper (T3U), Tertile 4 (T4)

Table 6.

Associations Between Occupational or Environmental Exposure to Pesticides and Colon Cancer, Rectal Cancer, or CRC Risk.

Group	Population	Country	Specific Population	Relative Risk summary	Reference
Occupational exposure	farm-related	US (Wisconsin)	farmers	PMR colon 0.96, rectum 1.13, all cohorts colon 0.87 p<0.05, rectum 1.03, 1905–1958 colon 0.89, rectum 1.27 p<0.05 PCMR high agricultural production, herbicides 1.45 p<0.05, insecticides 1.26⁺	Saftlas et al. 1987(Saftlas et al., 1987)
		US (Illinois)	farmers	OR colon 1.04 p 0.54⁺, rectum 1.01 (0.77–1.33) p 0.94	Keller, Howe, 1994(Keller and Howe, 1994)
		US (Kansas)	farmers	OR colon farmers that used herbicides for 6–15 years 2.0 (0.5–7.5)^*^{^}	Hoar et al. 1985(Hoar et al., 1985)
		US (California)	farmers	PMR colon 0.98, rectum 0.92⁺	Peterson, Milham, 1980(Peterson and Milham, 1980)
		US (Washington State)	farmers	PMR colon 0.88 p<0.05, rectum 0.94⁺	Milham 1989(Milham, 1983)
		US (Massachusetts)	farmers	MOR colon 2.33 p<0.05⁺	Dubrow, Wegman, 1984(Dubrow and Wegman, 1984)
		US (Iowa)	farmers	SMR colon 1.22 p<0.01, PMR 1.03⁺	Burmeister 1981(Burmeister, 1981)
		US (North Carolina)	farmers	PMR CRC whites 0.7 (0.6–0.8), non-whites 0.7 (0.5–1.0)^*	Delzell, Grufferman, 1985(Delzell and Grufferman, 1985)
		US (Missouri)	farmers	OR colon 0.86 (0.73–1.02), rectum 1.21 (0.95–1.53)^*	Brownson et al. 1989(Brownson et al., 1989)
		US (South Carolina)	farmers (male)	PMR CRC white 0.61 p<0.05, non-white 0.60 p<0.05⁺	Une et al. 1987(Une et al., 1987)
		US (California)	farm workers	OR colon 0.75 (0.53–1.05), rectum 0.85 (0.54–1.31)^*	Mills, Kwong, 2001(Mills and Kwong, 2001)
		US (New York)	farm bureau members	SMR colon 30–39 5.00, 40–49 0.39, 50–59 0.35 p<0.025, 60–69 0.55 p<0.025, 70⁺ 0.55 p<0.025, total 0.54 p<0.005⁺	Stark et al. 1987(Stark et al., 1987)
		US (California)	California Hispanic and United Farm Workers of America	CRC Male crude HR 1.61 (1.11–2.33) p-value <0.05, age and stage in model 1.35 (0.93–1.95)^, Female HR age and stage in model 1.01 (0.45–2.24)^	Dodge, Mills, Riordan, 2007(Dodge et al., 2007)
		US	farmers	PCMR colon non-white men 0.78 (0.66–0.92)^, white male south 0.91 p<0.05⁺, non-white male south 0.81 p<0.05*⁺	Blair, Dosimeci, Heinman, 1993(Blair et al., 1993)
		US	farmers	SMR colon 0.71 p<0.05, rectum 0.79⁺	Blair, Walrath, Rogot, 1985(Blair et al., 1985b)
		US	farmers	SMR colon 0.71 p<0.05, rectum 0.79⁺	Walrath et al. 1985(Walrath et al., 1985)
		US	farmers	OR CRC 0.58 p<0.05⁺	Decoufle et al. 1977(Decoufle and Stanislawczyk, 1977)
		US	farmers	SMR CRC 0.69⁺	Guralnick 1963(Guralnick, 1963)
		US	farmers/ farm laborers	RR male colon 1.24, rectum 0.77, female colon 1.42^*⁺	Williams, Stegens, Goldsmith, 1977(Williams et al., 1977)
		US	migrant and seasonal farmworkers	PCMR colon white men 0.87 (0.75–0.99), non-white men 0.72 (0.57–0.89), white women 1.18 (0.79–1.71), non-white women 0.76 (0.55–1.03), rectum white men 0.71 (0.48–1.02), non-white men 1.04 (0.64–1.59), white women 0.60 (0.07–2.18), non-white women 0.84 (0.31–1.83)^*	Colt et al. 2001(Colt et al., 2001)
		Italy	farmers, case-control	CRC Crude OR 3.389 (2.238–5.050) p-value <0.001, Generalized Linear Mixed Models OR 1.529 (1.011–2.314) p-value 0.044	Salerno et al. 2016(Salerno et al., 2016)
		Italy	farmers	Colon OR (90% CI) 0.93 (0.60–1.43)^, Rectum 1.45 (0.82–2.59)^, rectum non-farmers vs. >10 years 4.22 (1.08–14.7) p-value <0.10	Forastiere et al. 1993(Forastiere et al., 1993)
		Italy	farmers, multi-site case-control	farmers OR colon 0.8 (0.5–1.2), rectum 1.4 (0.8–2.7), production/application colon 0.8 (0.5–1.4), rectum 1.5 (0.8–2.9)^*^{^}	Settimi et al. 2001(Settimi et al., 2001)
		Italy	farmers/ agricultural workers	SMR male colon 0.76 (0.31–1.58), rectum 1.06 (0.34–2.49)	Faustini et al. 1993(Faustini et al., 1993)
		Italy	farmers	RR CRC males 0.6 (0.3–0.9), females 1.2 (0.7–2.0), total 0.8 (0.6–1.2)^*^{^}	Franceschi et al. 1993(Franceschi et al., 1993)
		Canada (Alberta)	farmers	OR CRC 1.02 (0.85–1.22)^*	Fincham, Hanson, Berkel, 1991(Fincham et al., 1992)
		Canada (British Columbia)	farmers	PMR colon 0.84 (0.75–0.93)^*	Gallagher et al. 1984(Gallagher et al., 1984)
		Canada	farmers, farm workers and agriculture	SMR colon farmers 0.53 p>0.05, agriculture 0.66 p>0.05⁺	Howe, Lindsay, 1983(Howe and Lindsay, 1983)
		Canada	agricultural workers	male HR colon 0.89 (0.82–0.97), rectum 1.05 (0.95–1.16), female HR colon 0.95 (0.82–1.10), rectum 1.08 (0.88–1.32)^*	Kachuri et al. 2017(Kachuri et al., 2017)
		Sweden	farmers	SIR colon 0.74 p<0.05, rectum 0.90⁺	Statistics Sweden 1981(Sweden, 1981)
		Sweden	farmers (female)	SIR colon 0.90 (0.81–1.00), rectum 0.86 (0.74–1.00)^*	Wiklund, Dich, 1994(Wiklund and Dich, 1994)
		Sweden	farmers	SIR colon 0.80 p<0.05, rectum 0.96⁺	Wiklund, Einhorn, Wennstrom, 1981(Wiklund et al., 1981)
		Denmark and Italy	farmers	male Denmark SIR colon 0.58 p-value <0.05, rectum 0.77 p-value <0.05, Italy CRC 0.46 p-value <0.05, female Denmark colon SIR 0.21 p-value <0.05, rectum 0.38^, Italy colorectal 0.31^⁺	Ronco, Costa, Lynge, 1992(Ronco et al., 1992)
		Denmark	farmers	colon farming adjusted OR men 0.5 (0.3–0.9), women 2.1 (0.6–7.6), both 0.7 (0.4–1.1), farming animals adjusted OR men 0.4 (0.2–0.8), women 2.0 (0.5–8.9), both 0.5 (0.3–0.9)^*^{^}	Kaerlev et al. 2004(Kaerlev et al., 2004)
		Australia	farmers and farm managers (male)	CRC SMR 1.37 (0.98–1.87)^*	Fragar, Depczynski, Lower, 2011(Fragar et al., 2011)
		Australia	farmers (male)	SRR colon 0.81 p<0.05, rectum 0.84 p<0.05⁺	McMichael, Hartshorne, 1982(McMichael and Hartshorne, 1982)
		Iceland	farmers	SIR colon 0.47 (0.26–0.77), rectum 0.93 (0.49–1.63)^*	Gunnarsdottir, Rafnsson, 1991(Gunnarsdottir and Rafnsson, 1991)
		Iceland	farmers	SMR colon 0.35 (0.07–1.02), rectum 1.06 (0.29–2.77)^*	Rafnsson, Gunnarsdottir, 1989(Rafnsson and Gunnarsdottir, 1989)
		UK (England and Wales)	farmers	SMR colon 1.20, rectum 1.00⁺	Fox, Goldblatt, 1980(Fox and Goldblatt, 1980)
		The Netherlands	farmers	PMR colon 0.78 p<0.05, rectum 0.90⁺	Versluys 1949(Versluys, 1949)
		New Zealand	farmers	OR colon 1.10 (0.97–1.25), rectum 1.19 (1.03–1.38)^*	Reif, Pearce, Fraser, 1989(Reif et al., 1989)
		Egypt	farmers	CRC adjusted OR pesticides 2.6 (1.1–5.9), insecticides 3.2 (1.5–6.5), herbicides 5.5 (2.4–12.3), eating from field 4.6 (1.5–14.6), working after spray 2.1 (0.7–5.9)^*^{^}	Lo et al. 2010(Lo et al., 2010)
		Denmark	Agriculture, forestry, fishing	SPIR women 1.15^*⁺	Olsen, Jensen, 1987(Olsen and Jensen, 1987)
		Sweden	market gardeners/orchardists	SMR mortality intestine 0.7 (0.4–1.4), tumor morbidity intestine 0.6 (0.3–1.0), rectum 0.9 (0.5–1.5)^*	Littorin et al. 1993(Littorin et al., 1993)
	Pesticide-related	Australia	Tick control outside workers	colon SMR 0.53 (0.20–1.16) SIR 0.52 (0.18–1.54), rectum SMR 1.62 (0.70–3.19) SIR 2.02 (0.52–7.86)^*	Beard et al. 2003(Beard et al., 2003)
		France	municipal pest-control workers	SMR colon 1.98 (0.05–11.04), rectum 5.57 (0.14–31.06)^*	Ambroise et al. 2005(Ambroise et al., 2005)
		US (Florida)	pesticide applicators	SMR colon male 0.81 (0.59–1.10), female 1.44 (0.58–2.97), rectum male 0.78 (0.31–1.60), female 1.19 (0.02–6.63)^*	Fleming et al. 1999a(Fleming et al., 1999a)
		US (Florida)	pesticide applicators	SIR colon male 0.70 (0.57–0.85), female 0.78 (0.37–1.44), rectum male 0.88 (0.66–1.15), female 0.56 (0.11–1.63)^*	Fleming et al. 1999b(Fleming et al., 1999b)
		US	pesticide applicators	SMR colon private 0.7 (0.6–1.0), total 0.8 (0.7–1.0)^*^{^}	Blair et al. 2005(Blair et al., 2005)
		US	pesticide applicators (male)	SMR digestive organs and peritoneum 0.84 (0.64–1.08)^*	MacMahon et al. 1988(MacMahon et al., 1988)
		US	pesticide applicators	RR colon 0.51 (0.3–0.9)^, rectum 0.68 (0.2–2.0)^, SMR colon aerial applicators 0.55 (0.31–0.91)^, flight instructors 1.12 (0.76–1.60)^, RR flight hours colon 0.49 p-trend 0.02	Cantor, Silberman 1999(Cantor and Silberman, 1999)
		US	pesticide applicators	SMR colon 1.05 (0.28–2.68), rectum 1.45 (0.02–8.07)^*	Zahm 1997(Zahm, 1997)
		US	pesticide applicators	SIR colon 0.88 (0.76–1.01), rectum 0.81 (0.65–0.99)^*	Alavanja et al. 2005(Alavanja et al., 2005)
		Italy	pesticide applicators	SMR colon provincial 0.74 (0.32–1.46), national 0.81 (0.35–1.59)^*	Figa-Talamanca et al. 1993(Figa-Talamanca et al., 1993)
		Italy	pesticide applicators	SMR colon regional 0.95 (0.61–1.42), national 0.82 (0.52–1.22)^*	Alberghini et al. 1991(Alberghini et al., 1991)
		Italy	pesticide applicators	SMR colon 0.57 (0.45–0.71)^*	Torchio et al. 1994(Torchio et al., 1994)
		The Netherlands	pesticide applicators	SMR colon 1.03 (0.41–2.11), rectum 2.08 (0.67–4.82)^*	Swaen et al. 2004(Swaen et al., 2004)
		The Netherlands	pesticide applicators	SMR colon 2.25 (0.69–6.54)^*	Swaen et al. 1992(Swaen et al., 1992)
		Iceland	pesticide applicators	colon SIR 0.62 (0.12–1.81), rectal SIR total cohort 2.94 (1.07–6.40), men 3.92 (1.06–10.04), total licensed to use pesticides 4.63 (1.49–10.80)^*	Zhong, Rafnsson, 1996(Zhong and Rafnsson, 1996)
		Sweden	pesticide applicators	SIR colon 0.81 (0.57–1.13), rectum 0.83 (0.54–1.21)^*	Wiklund et al. 1989(Wiklund et al., 1989)
		Finland	pesticide applicators	SMR 15-year latency colon 0.95 (0.12–3.42), rectum 0.53 (0.01–2.98), SIR colon 1.31 (0.42–3.05), rectum 0.57 (0.07–2.05)^*	Asp et al. 1994(Asp et al., 1994)
		New Zealand	pesticide manufacturers and applicators	SMR production workers colon 0.62 (0.08–2.25), rectum 2.45 (0.79–5.73), sprayers colon 1.94 (0.84–3.83), rectum 1.47 (0.40–3.76)^*	t Mannetje et al. 2005(‘t Mannetje et al., 2005)
		UK	pesticide manufacturers and applicators	SMR colon 1.00 (0.60–1.56), rectum 0.56 (0.24–1.10)^*	Coggon et al. 1986(Coggon et al., 1986)
		US (Alabama and Louisiana)	pesticide manufacturers	SMR other digestive system possible 1.08 (0.29–2.77), total 0.81 (0.26–1.88)^*	Sathiakumar, Delzell, Cole, 1996(Sathiakumar et al., 1996)
US (Michigan and Arkansas)		pesticide manufacturers (males)	SMR exposed to DDT colon 0.60 (0.01–3.32), rectum 1.56 (0.02–8.86)^*	Wong et al. 1984(Wong et al., 1984)
US (Colorado)		pesticide manufacturers	SMR CRC 1.15 (0.61–1.96)^*	Amoateng-Adjepong et al. 1995(Amoateng-Adjepong et al., 1995)
US (Louisiana)		pesticide manufacturers	SIR CRC white men 1.04 (0.21–3.04), company 1.30 (0.27–3.81), total 0.71 (0.15–2.06)^*	MacLennan et al. 2002(MacLennan et al., 2002)
US		pesticide manufacturers	SMR colon Plant 2 1.75, Plant 3 0.30, rectum Plant 1 1.78, Plant 3 2.42 (0.49–7.07)^*	Ditraglia et al. 1981(Ditraglia et al., 1981)
US		pesticide manufacturers	SMR digestive organs and peritoneum 0.86 (0.38–1.70)^*	Wang, MacMahon, 1979(Wang and Macmahon, 1979)
Germany		pesticide manufacturers	SIR CRC herbicide production 2.0 (0.2–7.2), maintenance 2.8 (0.1–16.0)^*^{^}	Nasterlack et al. 2007(Nasterlack et al., 2007)
Other occupations	US	chemical workers	SMR cancer of digestive organs and peritoneum 0.74 (0.43–1.21)^*	Burns, Beard, Cartmill, 2001(Burns et al., 2001)
	Denmark	factory workers	SIR colon men 1.03 (0.5–1.8), women 0.26 (0.01–1.4), rectum men 1.41 (0.8–2.4)^*^{^}	Lynge 1998(Lynge, 1998)
	The Netherlands	factory workers	SMR colon factory A 2.40 (0.49–7.01), exposed 1.83 (0.38–5.35)^*	Bueno de Mesquita et al. 1993(Bueno de Demesquita et al., 1993)
	International	workers	SMR exposed to TCDD or higher chlorinated dioxins colon 1.00 (0.75–1.31), rectum 1.32 (0.88–1.89), exposed to any phenoxy herbicide or chlorophenol colon 1.06 (0.85–1.31), rectum 1.06 (0.77–1.42)^*	Kogevinas et al. 1997(Kogevinas et al., 1997)
	Korea	Korean Vietnam veterans	SIR colon 1.03 (0.94–1.14), rectum 0.99 (0.91–1.08), colon enlisted soldiers 0.90 (0.80–1.02), non-commisioned officers 1.24 (1.01–1.53), officers 1.52 (1.22–1.89), rectum enlisted soldiers 1.05 (0.95–1.16), non-commisioned officers 0.81 (0.64–1.03), officers 0.89 (0.69–1.16)^*	Yi 2013(Yi, 2013)
	Korea	Korean Vietnam veterans	OR colon High exposure 2 groups 1.13 (1.01–1.26)^*, High exposure 4 groups 1.05 (0.88–1.24) p-trend 0.21	Yi et al. 2013(Yi et al., 2013)
	Korea	Korean Vietnam veterans	HR CRC 0.96 (0.78–1.19) p-value 0.723	Yi et al. 2014(Yi et al., 2014)
Environment al exposure	Geography-related	US	spouses of pesticide applicators	SIR colon 1.2 (0.8–1.6)^*	Blair et al. 2005(Blair et al., 2005)
		US	spouses of pesticide applicators	SIR colon 0.91 (0.73–1.12), rectum 0.59 (0.38–0.89)^*	Alavanja et al. 2005(Alavanja et al., 2005)
		UK	women in the United Kingdom	CRC RR never consumed organic food referent, usually/always 1.02 (0.93–1.12)^*	Bradbury et al. 2014(Bradbury et al., 2014)
		England	near herbicide/ pesticide production facility	CRC PMR 1.20^*⁺	Wilkinson et al. 1997(Wilkinson et al., 1997)
		US (New York)	farm residents	SIR CRC 0.65 (0.45–0.90)^*	Wang et al. 2002(Wang et al., 2002)
		US (New York)	farm residents	SMR CRC 0.56 (0.28–1.03)^*	Wang et al. 2003(Wang et al., 2003)
		Australia (New South Wales)	farm residents	OR CRC men rural non-farm vs. farm 0.45 (0.19–1.07), urban vs. farm 0.49 (0.21–1.17), women rural non-farm vs. farm 1.21 (0.47–3.09), urban vs. farm 0.92 (0.36–2.35)^*	Depczynski et al. 2018a(Depczynski et al., 2018b)
		Australia	farm residents	HR CRC men rural non-farm vs. farm 1.12 (0.86–1.46), urban vs. farm 1.02 (0.78–1.33), women rural non-farm vs. farm 1.03 (0.76–1.40), urban vs. farm 0.95 (0.70–1.29)^*	Depczynski et al. 2018b(Depczynski et al., 2018a)
		South Korea	near farms	CRC RR men 0.82 (0.76–0.89) p-trend <0.01, women 0.87 (0.81–0.94) p-trend 0.02	Lee et al. 2008(Lee et al., 2008)
		Spain	near farms	OR colon total 1.51 (1.42–1.61) p-value <0.001	Parron et al. 2014(Parron et al., 2014)
		Israel	Druze Isifya Village	CRC OR 0.67 (0.12–3.78)^*	Atzmon et al. 2012(Atzmon et al., 2012)
		Turkey	Secondary data: Antalya Cancer Registry Center	CRC women B Coefficient - 0.708, t −2.875, p-value 0.028	Uysal et al. 2013(Uysal et al., 2013)
		Brazil	Secondary data	colon SMR vs. 3 of pesticides sold per Brazilian state for each year (2000–2012) used to calculate effect (beta st): roughly around 0.1–0.15	Martin et al. 2018(Martin et al., 2018)
		Costa Rica	Secondary data from 81 counties	RR colon men 1.19 (0.78–1.81), women 1.65 (0.98–2.78), rectum men 1.61 (0.96–2.69) women 1.86 (1.06–3.25)^*	Wesseling et al. 1999(Wesseling et al., 1999)
	Food-related	US (New York)	Angler Cohort Study	adjusted RR CRC ever ate 0.66 (0.35–1.24)^, years of consumption 0.51 (0.22–1.18) p-trend 0.13, colon ever ate 0.45 (0.20–1.00)^, years of consumption 0.24 (0.07–0.87) p-trend 0.02, rectal ever ate 1.25 (0.43–3.65)^*, years of consumption 1.30 (0.37–4.58) p-trend 0.59	Callahan et al. 2017(Callahan et al., 2017)
	Food-related	France	NutriNet-Sante Prospective Cohort	HR CRC cancer 0.87 (0.48–1.57) p-value 0.84	Baudry, Assmann, Touvier, 2018(Baudry et al., 2018)

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Bolded Statistically significant.

No p-value listed in the publication.

^{^}

Only one or no decimal points reported in the original publication.

⁺

No CI listed in original publication.

3.2. Studies Analyzing Certain Pesticides Exposure and Colon Cancer, Rectal Cancer, and CRC Risk

There are a few different groups of pesticides, such as OCIs and OPIs, chlorophenoxy herbicides, carbamate insecticides, anilide/ aniline herbicides, and triazine herbicides. Of the 139 studies included, 48 evaluated certain pesticides. Significant associations between certain pesticide exposure and colon cancer, rectal cancer, and CRC risk from these 48 studies are discussed below and in Figures 2 through 4 and in more detail in Tables 2 through 5. The tables and figures are sorted by cancer or analysis type (Table 2 and Figure 2 colon cancer, Table 3 and Figure 3 rectal cancer, Table 4 and Figure 4 CRC, and Table 5 serum measurement analyses). The epidemiological studies included report their results in effect sizes in which a value of greater than 1 denotes a positive association while a value of less than 1 denotes an inverse association. The biological sample measurement studies included in this review reported their results as mean abundances, levels, or concentrations and we have calculated the fold changes (not reported, cancer/control) to denote the differences between groups studied and these are reported in Table 5. Because of these differences in reporting units and values, Figures 2–4 only report the significant results of epidemiological studies with CI reported included in this review.

Figure 2. — The pesticides aldicarb, dicamba, fonofos, EPTC, imazethapyr, terbufos, and trifluralin show positive associations while alachlor, lindane, 2,4-D, butylate, and DDT show inverse associations between pesticide exposure and colon cancer risk. Only significant associations from epidemiological studies with CI reported have been summarized in this figure. Associations from biological sample measurement studies can be found in Table 5.

Figure 4. — We have summarized that pesticides such as heptachlor, lindane, fonofos, and acetochlor have been shown to have significant positive associations, 2,4-D has been shown to have a significant inverse association, and alachlor and chlordane (one study not shown, biological sample measurement study) have been shown to have both significant positive and inverse associations with CRC risk. Only significant associations with CI reported from epidemiological studies have been summarized in this figure. Associations from biological sample measurement studies can be found in Table 5.

Table 5.

Serum Measurement-based Associations Between Pesticides and CRC Risk.

Pesticide	Pesticide level and p-value summary	Reference
DDT	mean (SD) pp-DDE CRC 230.95 (275.21) control 184.98 (205.39), pp-DDT CRC 8.49 (10.35) control 8.31 (7.17), p-values >0.05	Abdallah, Zaky, Covaci, 2017(Abdallah et al., 2017)
	mean (SD) 2,4 DDE CRC 8.18 (4.69) control 3.95 (2.60), 4,4 DDE CRC 15.32 (8.75) control 0.68 (0.33), 2,4 DDT CRC 31.19 (6.47) control 3.47 (1.89), 4,4 DDT CRC 44.47 (9.56) control 2.13 (0.89), p-values <0.001	Abolhassani et al. 2019(Abolhassani et al., 2019)
	mean (SE) o,p’-DDE control 189.8 (22.6) polyp 234.1 (23.1) CRC 320.0 (34.6) p 0.01, p,p’-DDE control 174964.9 (17319.1) polyp 184837.3 (15165.3) CRC 176523.1 (15909.4) p 0.89, o,p’-DDT control 202.2 (22.4) polyp 246.7 (22.6) CRC 269.1 (27.1) p 0.19, p,p’-DDT control 7155.1 (1122.4) polyp 6662.8 (866.3) CRC 7546.8 (1077.9) p 0.82	Lee et al. 2018(Lee et al., 2018)
	mean (SD) DDT cancer 71 (131.9) noncancer 61.5 (51.6) rectal 48.4 (65.3) colon 92.3 (172.6) p-values >0.05	Soliman et al. 1997(Soliman et al., 1997)
HCB	mean (SD) CRC 6.37 (3.85) control 6.60 (4.81), p-values >0.05	Abdallah, Zaky, Covaci, 2017(Abdallah et al., 2017)
gamma HCH (lindane)	mean (SD) alpha HCH CRC 11.76 (9.82) control 1.37 (0.69), beta HCH CRC 3.65 (2.26) control 0.51 (0.15), gamma HCH CRC 6.90 (7.91) control 0.37 (0.11), p-values <0.001	Abolhassani et al. 2019(Abolhassani et al., 2019)
	mean (SE) beta HCH control 12679.1 (1562.3) polyp 18610.2 (1900.7) CRC 16696.9 (1873.3) p-value 0.05	Lee et al. 2018(Lee et al., 2018)
	mean (SD) beta HCH cancer 21.5 (57.4) noncancer 10.5 (13.0) rectal 16.8 (22.8) colon 26 (77.9) p-values >0.05	Soliman et al. 1997(Soliman et al., 1997)
chlordane	mean (SD) oxychlordane CRC 2.10 (0.93) control 1.87 (0.89), p-values >0.05	Abdallah, Zaky, Covaci, 2017(Abdallah et al., 2017)
chlordane	mean (SE) trans-chlordane control 90.9 (10.6) polyp 105.6 (10.2) CRC 100.1 (10.6) p 0.61, oxychlordane control 750.9 (163.2) polyp 523.4 (94.3) CRC 4079.3 (807.3) p<0.01	Lee et al. 2018(Lee et al., 2018)
PCP	mean (SD) CRC 33.26 (45.87) control 28.73 (35.48), p-values >0.05	Abdallah, Zaky, Covaci, 2017(Abdallah et al., 2017)
nonachlor	mean (SE) trans-nonachlor control 5902.4 (747.2) polyp 6704.3 (703.4) CRC 7612.3 (877.4) p 0.39, cis-nonachlor control 556.3 (118.5) polyp 335.9 (59.3) CRC 738.2 (143.1) p 0.01	Lee et al. 2018(Lee et al., 2018)
heptachlor	mean (SE) heptachlor epoxide control 609.4 (112.7) polyp 719.6 (110.3) CRC 2179.2 (366.9) p <0.01, heptachlor control 188.7 (30.2) polyp 448.4 (59.5) CRC 260.6 (38.0) p <0.01	Lee et al. 2018(Lee et al., 2018)

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Results that were statistically significant were bolded under the pesticide level and p-value summary.

No p-value listed in the publication.

^{^}

Only one or no decimal points reported in the original publication. Standard deviation (SD), standard error (SE).

Table 3.

Associations Between Pesticide Exposure and Rectal Cancer Risk.

Type	Group	Pesticide	Effect size summary	Reference
Insecticides	Organochlorine	Chlordane	RR 1.80 (0.77–4.21)^*	Louis et al. 2017(Louis et al., 2017)
			LED RR 2.7 (1.1–6.8) p-trend 0.03^{^}	Purdue et al. 2007(Purdue et al., 2007)
			OR 1.6 (0.97–2.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Heptachlor	OR 1.3 (0.7–2.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Aldrin	OR 1.4 (0.8–2.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Dieldrin	OR 1.2 (0.6–2.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Aldrin and Dieldrin	SMR 1.76 (0.21–6.34)^*^{^}	van Amelsvoort et al. 2009(van Amelsvoort et al., 2009)
		Aldrin and Dieldrin	SMR 3.00 (1.10–6.49) p<0.05	Swaen et al. 2002(Swaen et al., 2002)
		Toxaphene	0 vs. T3 OR 4.3 (1.2–15.8) p-trend 0.123, OR 2.1 (1.2–3.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Pentachlorophenol and Tetrachlorophenol	SMR 1.10 (0.82–1.43), SIR 1.08 (0.92–1.29)^*	Demers et al. 2006(Demers et al., 2006)
		DDT	PMR 0.38 (0.04–1.37)^*^{^}	Cocco et al. 1997(Cocco et al., 1997)
			RR 1.79 (0.76–4.22)^*	Louis et al. 2017(Louis et al., 2017)
			OR 1.0 (0.6–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Lindane (gamma HCH)	male SIR 0.61 (0.44–0.83)^*	Rafnsson 2006(Rafnsson, 2006)
		Lindane (gamma HCH)	OR 1.1 (0.6–2.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Carbon tetrachloride/carbon disulfide	OR 1.1 (0.5–2.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organophosphate	Trichlorfon	OR 1.5 (0.2–10.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Dichlorovos	OR 0.8 (0.4–2.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Chlorpyrifos	RR LED 0 vs. T4 3.25 (1.60–6.62) p-trend 0.035, IWLED 0 vs. T4 3.16 (1.42–7.03) p-trend 0.057	Lee et al. 2004a(Lee et al., 2004a)
		Chlorpyrifos	0 vs. T4 OR 2.7 (1.2–6.4) p-trend 0.008, OR 1.4 (0.9–2.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Terbufos	OR 0.8 (0.5–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Fonofos	OR 1.1 (0.6–2.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Malathion	OR 1.0 (0.6–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Parathion	OR 0.9 (0.5–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Phorate	OR 1.0 (0.6–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Coumaphos	OR 0.9 (0.4–2.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Diazinion	OR 1.3 (0.8–2.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Carbamate	Aldicarb	OR 0.8 (0.4–1.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Carbofuran	OR 1.2 (0.7–2.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Carbaryl	OR 2.0 (1.1–3.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Butylate	OR 0.8 (0.5–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Maneb/mancozeb	OR 0.9 (0.4–2.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Ziram	OR 2.3 (0.7–7.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Pyrethroid	Permethrin	LED RR 0.78 (0.31–1.92) p-trend 0.29	Rusiecki et al. 2009(Rusiecki et al., 2009)
	Pyrethroid	Permethrin	crops OR 0.5 (0.2–1.3), livestock OR 1.4 (0.7–2.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organobromine	Ethylene dibromide	OR 0.6 (0.1–2.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Other	Petroleum oil	OR 0.9 (0.5–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
Herbicides	Chlorophenoxy	2,4,5-TP	OR 1.3 (0.7–2.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		2,4,5-T	OR 1.1 (0.6–1.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		2,4-D	OR 1.1 (0.6–2.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		2,4-D and MCPA	white men SRR 1.32 (1.04–1.67), white women SRR 1.12 (0.81–1.57)	Schreinemachers 2000(Schreinemachers, 2000)
		Dicamba	OR 0.8 (0.5–1.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Anilides/ anilines	Acetochlor	RR 0.97 (0.48–1.95) p>0.05	Lerro et al. 2015(Lerro et al., 2015b)
		Alachlor	SIR 1.60 (0.19–5.80)^*	Acquavella et al. 2004(Acquavella et al., 2004)
			SIR 0.64 (0.42–0.94)^*, LED RR 0.71 (0.16–3.11) p-trend 0.77, IWLED RR 1.07 (0.23–5.07) p-trend 0.83	Lee et al. 2004b(Lee et al., 2004b)
			OR 0.9 (0.5–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Metolachlor	OR 1.0 (0.6–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Pendimethalin	RR 4.3 (1.5–12.7) p-trend 0.007^{^}	Hou et al. 2006(Hou et al., 2006)
		Pendimethalin	OR 1.0 (0.6–1.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Trifluralin	LED RR 0.66 (0.22–1.99) p-trend 0.944, IWLED T1 vs. T3U RR 1.43 (0.52–3.92) p-trend 0.317	Kang et al. 2008(Kang et al., 2008)
		Trifluralin	OR 0.8 (0.5–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Trazines	Atrazine	RR 1.14 (0.66–1.96) p-trend 0.60	Beane Freeman et al. 2011(Beane Freeman et al., 2011)
			LED RR 1.38 (0.47–4.02) p-trend 0.65, IWLED RR 0.84 (0.29–2.44) p-trend 0.79	Rusiecki et al. 2004(Rusiecki et al., 2004)
			OR 1.2 (0.7–2.0)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Cyanizine	OR 1.4 (0.8–2.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Metribuzin	OR 0.9 (0.5–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Thiocarbamate	EPTC	LED RR 1.0 (0.42–2.40) p-trend 0.91	van Bemmel et al. 2008(van Bemmel et al., 2008)
	Thiocarbamate	EPTC	OR 0.9 (0.4–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Pyridine	Imazethapyr	RR 0.77 (0.39–1.51) p-trend 0.81	Koutros et al. 2009(Koutros et al., 2009)
	Pyridine	Imazethapyr	OR 0.9 (0.5–1.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Sulfonylurea	Chlorimuron ethyl	OR 1.0 (0.6–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organophosphate	Glyphosate	LED RR 1.1 (0.6–2.3) p-trend 0.70, IWLED RR 0.9 (0.5–1.9) p-trend 0.82^{^}	De Roos et al. 2005(De Roos et al., 2005)
	Organophosphate	Glyphosate	OR 1.6 (0.9–2.9)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Dipyridylium	Paraquat	OR 1.5 (0.8–2.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
Fungicides	Benzimazole	Benomyl	OR 1.2 (0.6–2.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Phthalimide	Captan	OR 1.1 (0.5–2.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organochlorine	Chlorothalonil	OR 0.7 (0.3–1.7)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Acylalanine	Metalaxyl	OR 1.0 (0.5–1.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
Fumigants	Other	Aluminum phosphide	OR 1.4 (0.6–3.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Methyl bromide	IWLED 1.38 (0.53–3.63) p-trend 0.48	Barry et al. 2012(Barry et al., 2012)
		Methyl bromide	OR 1.1 (0.6–2.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)

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Results that were statistically significant were bolded under the effect size summary.

No p-value listed in the publication.

^{^}

Only one or no decimal points reported in the original publication.

Figure 3. — This figure shows that pesticides such as toxaphene, pendimethalin, dieldrin and aldrin, chlorpyrifos, chlordane, carbaryl, and 2,4-D and MCPA have been reported to have positive associations while alachlor and lindane has been reported to have an inverse association with rectal cancer risk. Only significant associations from epidemiological studies with CI reported have been summarized in this figure. Associations from biological sample measurement studies can be found in Table 5. *These studies analyzed the association of concurrent dieldrin and aldrin and concurrent 2,4-D and MCPA exposure on rectal cancer risk.

Table 4.

Associations Between Pesticide Exposure and CRC Risk.

Type	Group	Pesticide	Effect size summary	Reference
Insecticides	Organochlorine	Chlordane	0 vs. T1 OR 0.5 (0.2–0.9) p-trend 0.545^{^}, OR 0.9 (0.7–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Chlordane	OR polyps 1.0 (0.4–2.4) p-trend 0.94, CRC 2.3 (0.8–6.7) p-trend 0.02^{^}	Lee et al. 2018(Lee et al., 2018)
		Heptachlor	OR 0.9 (0.6–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Heptachlor	OR polyps 1.8 (0.9–3.7) p-trend 0.11, CRC 6.5 (2.7–15.6) p-trend <0.01^{^}	Lee et al. 2018(Lee et al., 2018)
		Aldrin	OR 0.8 (0.6–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Dieldrin	OR 0.8 (0.5–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Toxaphene	OR 1.3 (0.96–1.9)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		DDT	p,p’-DDT OR 0.56 (0.27–1.17) p-trend 0.12, p,p’-DDE OR 1.60 (0.79–3.25) p-trend 0.19	Howsam et al. 2004(Howsam et al., 2004)
			OR 0.9 (0.7–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
			OR polyps 1.2 (0.5–2.9) p-trend 0.52 CRC 2.4 (0.8–6.8) p-trend 0.09^{^}	Lee et al. 2018(Lee et al., 2018)
		Lindane (gamma HCH)	Lindane (gamma HCH) OR 0.69 (0.34–1.38) p-trend 0.28, alpha HCH OR 2.02 (0.95–4.29) p-trend 0.081, beta HCH OR 0.88 (0.39–2.02) p-trend 0.81	Howsam et al. 2004(Howsam et al., 2004)
			OR 0.8 (0.6–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
			ORs beta HCH polyps 6.0 (2.1–16.9) p-trend <0.01, CRC 3.7 (1.1–12.5) p-trend 0.11^{^}	Lee et al. 2018(Lee et al., 2018)
		Carbon tetrachloride/carbon disulfide	OR 0.8 (0.5–1.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organophosphate	Trichlorfon	OR 1.5 (0.5–4.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Dichlorovos	OR 1.3 (0.8–1.9)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Chlorpyrifos	RR 0.95 (0.56–1.61)^*	Lee et al. 2007a(Lee et al., 2007a)
			RR 0.87 (0.63–1.21)^*	Lee et al. 2004a(Lee et al., 2004a)
			OR 0.9 (0.7–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Terbufos	OR 0.9 (0.7–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Fonofos	0 vs. T3 OR 2.1 (1.2–3.7) p-trend 0.125^{^}, OR 1.4 (1.0–1.9)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Malathion	RR 0.84 (0.48–1.48) p-trend 0.48	Bonner et al. 2007(Bonner et al., 2007)
		Malathion	OR 0.8 (0.6–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Parathion	OR 0.9 (0.6–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Phorate	OR 1.1 (0.8–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Coumaphos	RR 0.84 (0.37–1.89) p-trend 0.49	Christensen et al. 2010(Christensen et al., 2010)
		Coumaphos	OR 1.0 (0.6–1.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Diazinion	LED RR 1.21 (0.43–3.45) p-trend 0.61, IWLED RR 0.53 (0.13–2.23) p-trend 0.55	Beane Freeman et al. 2005(Beane Freeman et al., 2005)
		Diazinion	OR 0.8 (0.6–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Carbamate	Aldicarb	OR 1.6 (1.0–2.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Carbofuran	OR 1.0 (0.8–1.4)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Carbaryl	OR 1.1 (0.8–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Butylate	OR 0.9 (0.7–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Maneb/mancozeb	OR 0.7 (0.5–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Ziram	OR 1.2 (0.5–2.9)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Pyrethroid	Permethrin	crop OR 0.8 (0.5–1.2), livestock OR 1.4 (0.9–2.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organobromine	Ethylene dibromide	OR 0.6 (0.3–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Other	Petroleum oil	OR 0.9 (0.7–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
Herbicides	Chlorophenoxy	2,4,5-TP	OR 0.8 (0.5–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		2,4,5-T	OR 0.9 (0.7–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		2,4-D	OR 0.7 (0.5–0.9)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Dicamba	OR 0.9 (0.7–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Anilides/ anilines	Acetochlor	RR 1.03 (0.69–1.53) p>0.05, RR 0.87 (0.38–1.99) p-value>0.05, LED RR 1.75 (1.08–2.83) p-value <0.05 p-trend 0.07, IWLED RR 1.59 (0.95–2.64) p-value <0.01 p-trend 0.16	Lerro et al. 2015(Lerro et al., 2015b)
		Alachlor	SIR 1.9 (0.4–5.6)^*^{^}	Acquavella et al. 1996(Acquavella et al., 1996)
			SIR 0.72 (0.58–0.89) ^*	Lee et al. 2004b(Lee et al., 2004b)
			colon, rectum, rectosigmoid junction, and anus: SIR 3.4 (0.7–10.0), 5+ years exposure/10 year lag SIR 10.3 (2.1–30.2)^*^{^}	Leet et al. 1996(Leet et al., 1996)
			OR 0.8 (0.6–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Metolachlor	OR 1.0 (0.8–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Pendimethalin	RR 1.0 (0.3–3.4) p-trend 0.7^{^}	Hou et al. 2006(Hou et al., 2006)
		Pendimethalin	OR 1.1 (0.8–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Trifluralin	OR 0.9 (0.7–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Trazines	Atrazine	RR 0.91 (0.67–1.23) p-value>0.05	Lerro et al. 2015(Lerro et al., 2015b)
		Atrazine	OR 0.9 (0.7–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Cyanizine	OR 1.0 (0.7–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
		Metribuzin	OR 0.8 (0.6–1.1)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Thiocarbmate	EPTC	OR 1.1 (0.8–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Pyridine	Imazethapyr	OR 1.1 (0.8–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Sulfonylurea	Chlorimuron ethyl	OR 0.8 (0.6–1.2)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organophosphate	Glyphosate	OR 1.2 (0.9–1.6)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Dipyridylium	Paraquat	OR 0.9 (0.7–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
Fungicides	Benzimazole	Benomyl	OR 0.9 (0.6–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Phthalimide	Captan	0 vs. T3 RR 0.71 (0.32–1.60) p-trend 0.10, T1 vs. T3 RR 0.51 (0.17–1.54) p-trend 0.11	Greenburg et al. 2008(Greenburg et al., 2008)
	Phthalimide	Captan	OR 0.8 (0.5–1.3)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organochlorine	Chlorothalonil	OR 1.2 (0.8–1.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
	Organochlorine	Hexachlorobenzene	OR 1.60 (0.62–4.15) p-trend 0.23	Howsam et al. 2004(Howsam et al., 2004)
	Acylalanine	Metalaxyl	OR 1.0 (0.7–1.5)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
Fumigants	Other	Aluminum phosphide	OR 0.9 (0.5–1.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)
Fumigants	Other	Methyl bromide	OR 1.3 (0.9–1.8)^*^{^}	Lee et al. 2007b(Lee et al., 2007b)

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Results that were statistically significant were bolded under the effect size summary.

No p-value listed in the publication.

^{^}

Only one or no decimal points reported in the original publication.

3.2.1. Organochlorine Insecticides

Among OCIs, toxaphene (Lee et al., 2007b), aldrin and dieldrin concurrently (Swaen et al., 2002) have shown significant positive associations with rectal cancer risk, and heptachlor has shown a significant positive association with CRC risk (Lee et al., 2018). DDT showed a significant inverse association with colon cancer risk (Cocco et al., 1997) but also the metabolite of DDT, DDE, showed a significant positive association with CRC risk (Lee et al., 2018). Lindane showed significant inverse associations with both colon and rectal cancer risk (Rafnsson, 2006) but also showed a significant positive association with CRC risk (Lee et al., 2018). Chlordane showed a significant positive association with rectal cancer risk (Purdue et al., 2007) but also showed both a significant positive association (Lee et al., 2018) and a significant inverse association with CRC risk (Lee et al., 2007b). Also, nonachlor, an impurity of chlordane, has shown a significant positive association with CRC risk (Lee et al., 2018). As you can see, varying studies have found opposing results for certain pesticide exposure effects on CRC risk. These mainly positive associations (seven out of eleven) among rectal cancer and CRC risk and OCIs are understandable as DDT, lindane, chlordane, toxaphene, heptachlor, dieldrin, and aldrin are all banned or severely restricted in the US and other countries (Donley, 2019; PAN, 2020) (Table 1) based on health issues that have been shown to correlate with exposure to these pesticides. However, DDT, chlordane, and dieldrin have still been detected on imported foods as recently as 2018 (FDA, 2018) (Table 1).

3.2.2. Organophosphate Insecticides

Terbufos showed a significant positive association with colon cancer risk (Bonner et al., 2010), chlorpyrifos showed significant positive associations with rectal cancer risk (Lee et al., 2004a; Lee et al., 2007b), and fonofos showed significant positive associations with colon cancer and CRC risk (Lee et al., 2007b). These positive associations are of interest because terbufos and chlorpyrifos have no restriction in the US (Donley, 2019; PAN, 2020), have been used in the US as recently as 2017 (USGS, 2017), and chlorpyrifos is still detected on imported food products as recently as 2018 (FDA, 2018) (Table 1).

3.2.3. Carbamate Insecticides

Among carbamate insecticides, aldicarb (Lee et al., 2007b) showed a positive association and butylate showed an inverse association with colon cancer risk (Lynch et al., 2009), and carbaryl showed a positive association with rectal cancer risk (Lee et al., 2007b). These mainly positive associations are of interest because aldicarb is banned in the US (Donley, 2019; PAN, 2020) but was still being used in the US as of 2017 (USGS, 2017) and carbaryl is not banned in the US (Donley, 2019; PAN, 2020) (Table 1).

3.2.4. Chlorophenoxy Herbicides

MCPA and 2,4-D used concurrently were shown to have a significant positive association with rectal cancer risk (Schreinemachers, 2000), dicamba was shown to have a significant positive association with colon cancer risk (Samanic et al., 2006), and 2,4-D was shown to have significant inverse associations with both colon cancer and CRC risk (Lee et al., 2007b). These results are of concern because although 2,4-D and MCPA are currently banned in other countries, and 2,4-D is classified as a possible human carcinogen (WHO, 2020), they are not banned in the US and dicamba is not banned anywhere (Donley, 2019; PAN, 2020) (Table 1).

3.2.5. Anilide/ Aniline Herbicides

Of the anilide/ aniline herbicide exposures studied, significant positive associations were reported between trifluralin and colon cancer risk (Kang et al., 2008), pendimethalin and rectal cancer risk (Hou et al., 2006), and acetochlor and CRC risk (Lerro et al., 2015b). Alachlor exposure has been shown to have significant inverse associations with colon and rectal cancer risk (Lee et al., 2004b), and both a significant inverse association (Lee et al., 2004b) and a significant positive association (Leet et al., 1996) with CRC risk. These mostly positive associations are worthy of note because acetochlor and trifluralin are banned in other countries but not in the US, pendimethalin currently has unrestricted use worldwide except for Norway, and alachlor has been banned in the US (Donley, 2019; PAN, 2020) but was still being used in the US as recently as 2017 (USGS, 2017) (Table 1).

3.2.6. Other Pesticides

Of the other pesticides studied in these publications imazethapyr, a pyridine herbicide, (Koutros et al., 2009) and EPTC, a thiocarbamate herbicide, (van Bemmel et al., 2008) have been shown to have significant positive associations with colon cancer risk. These positive associations are also of public health interest because imazethapyr and EPTC are banned in other countries but not in the US (Donley, 2019; PAN, 2020) (Table 1). No significant associations were found between pyrethroid and organobromine insecticides, triazine, sulfonylurea, organophosphate, or dipyridylium herbicides, fungicides or fumigants and colon cancer, rectal cancer, or CRC risk.

3.2.7. Discussion of Pesticide Exposure and Colon Cancer Risk

In this review, seven pesticides, aldicarb (Lee et al., 2007b), dicamba (Samanic et al., 2006), fonofos (Lee et al., 2007b), EPTC (van Bemmel et al., 2008), imazethapyr (Koutros et al., 2009), terbufos (Bonner et al., 2010), and trifluralin (Kang et al., 2008) had significant medium to large positive associations with colon cancer risk (Figure 2). This is of concern because imazethapyr, terbufos, EPTC, and trifluralin are banned in other countries but not the US (Donley, 2019; PAN, 2020), aldicarb has been shown to be used in the US as recent as 2017 (USGS, 2017), and dicamba is not banned in any country (Donley, 2019; PAN, 2020) (Table 1). Also, five pesticides in this review had significant small to medium inverse associations with colon cancer risk: alachlor (Lee et al., 2004b), lindane (Rafnsson, 2006), 2,4-D (Lee et al., 2007b), butylate (Lynch et al., 2009), and DDT (Cocco et al., 1997) (Figure 2). Overall, there were more significant positive associations (7) between certain pesticides and colon cancer risk than inverse associations (5).

3.2.8. Discussion of Pesticide Exposure and Rectal Cancer Risk

Nine pesticides had significant positive associations with rectal cancer risk, including toxaphene (Lee et al., 2007b), pendimethalin (Hou et al., 2006), dieldrin and aldrin concurrently (Swaen et al., 2002), chlorpyrifos (Lee et al., 2007b), chlordane (Purdue et al., 2007), carbaryl (Lee et al., 2007b), and 2,4-D and MCPA concurrently (Schreinemachers, 2000) (Figure 3). Of these nine pesticides, seven, toxaphene, pendimethalin, dieldrin and aldrin (concurrently), chlorpyrifos, chlordane, and carbaryl, had medium or large, significant positive associations with rectal cancer risk. This is of concern because carbaryl and pendimethalin are not banned in any countries, including the US (Donley, 2019; PAN, 2020) (Table 1). Also, lindane (Rafnsson, 2006) and alachlor (Lee et al., 2004b) had small, significant inverse associations with rectal cancer risk (Figure 3). Therefore, overall more pesticides were found to be significantly positively associated (9) with rectal cancer risk than the number of those significantly inversely associated (2).

3.2.9. Discussion of Pesticide Exposure and CRC Risk

There were also studies that grouped colon and rectal cancer together into what is called colorectal cancer (CRC) and analyzed how certain pesticide exposure was associated with the risk of CRC. The pesticides and pesticide metabolites that were found to have significant positive association with CRC risk were fonofos (Lee et al., 2007b), DDT and DDE, metabolite of DDT, (Abolhassani et al., 2019; Lee et al., 2018), lindane (Abolhassani et al., 2019), heptachlor (Lee et al., 2018), and acetochlor (Lerro et al., 2015b) (epidemiological results found in Figure 4). Four of these had medium or large, significant positive associations with CRC risk: fonofos (Lee et al., 2007b), lindane (Abolhassani et al., 2019; Lee et al., 2018), heptachlor (Lee et al., 2018), and acetochlor (Lerro et al., 2015b) (Figure 4). This is of concern because acetochlor is not banned in the US (Donley, 2019; PAN, 2020) (Table 1). Also, 2,4-D was found to have a significant inverse association with CRC risk (Lee et al., 2007b) (Figure 4). In addition, chlordane (Lee et al., 2007b; Lee et al., 2018) and alachlor (Lee et al., 2004b; Leet et al., 1996) were found to have both significant positive and inverse associations with CRC risk (epidemiological study significant findings reported in Figure 4). Overall, more pesticides were found to be significantly positively associated (7) with CRC risk than the number that were found to be significantly inversely associated (3).

3.2.10. Summary of Pesticide Exposure and Colon Cancer, Rectal Cancer, and CRC Risk

From this systematic review, we found that there were 26 significant positive associations and 10 significant inverse associations reported with respect to exposure to specific pesticides and colon cancer, rectal cancer, or CRC risk. Exposure to pesticides such as aldicarb, dicamba, fonofos, EPTC, imazethapyr, terbufos, and trifluralin are positively associated with colon cancer risk (Figure 2), while toxaphene, pendimethalin, dieldrin and aldrin concurrently, chlorpyrifos, and carbaryl are positively associated with rectal cancer risk (Figure 3), and heptachlor, fonofos, and acetochlor are positively associated with CRC risk (Figure 4). This is of concern because many of these pesticides are not banned in the US (terbufos, dicamba, trifluralin, EPTC, imazethapyr, chlorpyrifos, carbaryl, pendimethalin, and acetochlor) (Donley, 2019; PAN, 2020), have been used as recently as 2017 in the US (aldicarb) (USGS, 2017), or have been detected on imported food as recently as 2018 (dieldrin) (FDA, 2018) (Table 1). We have also found that exposure to butylate has been shown to have a significant inverse association with colon cancer risk (Figure 2).

From our review, we have found conflicting results on the DDT, lindane, 2,4-D, alachlor, and chlordane exposure and CRC risk. DDT has been shown to have a significant inverse association with colon cancer risk (Cocco et al., 1997) but DDT and DDE have also been shown to have significant positive associations with CRC risk (Abolhassani et al., 2019; Lee et al., 2018). Lindane has been shown to have significant inverse associations with colon and rectal cancer risks (Rafnsson, 2006) but also has been shown to have significant positive associations with CRC risk (Abolhassani et al., 2019). 2,4-D has been found to have significant inverse associations with colon cancer and CRC risks (Lee et al., 2007b) but also significant positive associations with rectal cancer risk when used concurrently with MCPA (Schreinemachers, 2000). Alachlor was found to have significant inverse associations with colon and rectal cancer risks (Lee et al., 2004b) but also found to have both significant inverse associations (Lee et al., 2004b) and significant positive associations with CRC risk (Leet et al., 1996). Chlordane was found to have a significant positive association with rectal cancer risk (Purdue et al., 2007) but also both a significant positive association (Lee et al., 2018) and a significant inverse association with CRC risk (Lee et al., 2007b).

3.3. Studies Analyzing the Association between General Pesticide Exposure and Colon Cancer, Rectal Cancer, and CRC Risk

There were studies that focus on occupational or environmental exposure to pesticides and the association with colon cancer, rectal cancer, or CRC risk. In these studies, exposure to certain pesticides was not assessed but instead the overall pesticide exposure was analyzed. Of the 139 studies included in this review, 91 fall into this category. All comprehensive, summarized results are discussed in Table 6 and statistically significant results are discussed below and summarized in Figures 5–7 based on exposure type.

Figure 5. — We have summarized that pesticide exposure from farming or agricultural work have been shown to have either weak or no associations with colon cancer, rectal cancer or CRC risk.

Figure 7. — We have summarized that environmental pesticide exposure have been shown to have either weak or no associations with colon cancer, rectal cancer or CRC risk.

3.3.1. Occupational Pesticide Exposure and the Association with Colon Cancer, Rectal Cancer, and CRC Risk

Among the at-risk populations included in this review are farmers, farm residents, pesticide applicators or manufacturing workers, Korean veterans of the Vietnam war, those exposed via food, and those exposed in the community. Various studies analyzing the association between farmer’s exposure to pesticides and colon cancer, rectal cancer, and CRC risk have found both significant positive and inverse associations (Figure 5). It has been reported that farmers in Massachusetts (Dubrow and Wegman, 1984) and Iowa (Burmeister, 1981) have shown significant positive associations with colon cancer risk. In addition, farmers in Wisconsin (Saftlas et al., 1987), Italy (Forastiere et al., 1993), and New Zealand (Reif et al., 1989) have been reported to have significant positive associations with rectal cancer risk. Also, significant positive associations with CRC risk have been found among farmers in California (Dodge et al., 2007), Italy (Salerno et al., 2016), and Egypt (Lo et al., 2010). However, studies including farmers in Canada (Gallagher et al., 1984; Kachuri et al., 2017), Sweden (Sweden, 1981; Wiklund et al., 1981), Denmark (Kaerlev et al., 2004; Ronco et al., 1992), Australia (McMichael and Hartshorne, 1982), Iceland (Gunnarsdottir and Rafnsson, 1991), The Netherlands (Versluys, 1949), Wisconsin (Saftlas et al., 1987), Washington State (Milham, 1983), New York (Stark et al., 1987), and other US populations (Blair et al., 1993; Blair et al., 1985b; Colt et al., 2001; Walrath et al., 1985) have found significant inverse associations with colon cancer risk. In addition, significant inverse associations with rectal cancer risk were reported in farmers from Denmark (Ronco et al., 1992) and Australia (McMichael and Hartshorne, 1982). Finally, farmers from Italy (Franceschi et al., 1993; Ronco et al., 1992), North Carolina (Delzell and Grufferman, 1985), South Carolina (Une et al., 1987), and another US population (Decoufle and Stanislawczyk, 1977) were found to have significant inverse associations with CRC risk. Previously, the reported inverse association among farmers and their CRC risk had been explained by their lower tobacco use and higher physical activity (Garabrant et al., 1984).

In addition to farmers, pesticide applicators are also perceived as being at increased risk of pesticide exposure, but from the studies reviewed, only one study reported a significant positive association with rectal cancer risk among Icelandic pesticide applicators (Zhong and Rafnsson, 1996). However, significant inverse associations were found between pesticide applicators in Italy (Torchio et al., 1994), Florida (Fleming et al., 1999b), and other US populations (Alavanja et al., 2005; Cantor and Silberman, 1999) and colon and rectal cancer risk. Other occupational risk factors include chemicals used at the job and chemical weapons used during wars. During the Vietnam War, Agent Orange was used, and three studies in this review looked at the association between that exposure and colon cancer risk. From this analysis, Agent Orange exposure was reported to have a significant positive association with colon cancer risk (Yi, 2013; Yi et al., 2013). These significant associations between occupational pesticide exposure and colon and rectal cancer risk are summarized in Figure 6.

Figure 6. — We have summarized that occupational pesticide exposure has been shown to have either weak or no associations with colon cancer, rectal cancer or CRC risk.

3.3.2. Environmental Pesticide Exposure and the Association with Colon Cancer, Rectal Cancer, and CRC Risk In addition to occupational exposure, there were other populations environmentally exposed to pesticides,

including those that ate food that may have been exposed to pesticides, those who live in rural communities near farms, farm residents, and spouses of pesticide applicators. The resulting significant associations with environmental exposure and colon cancer, rectal cancer and CRC risk can be seen in Figure 7. Significant positive associations were found between people living near farms in Spain and colon cancer risk (Parron et al., 2014) as well as among populations in Costa Rica and rectal cancer risk (Wesseling et al., 1999). However, significant inverse associations have been found between food-related exposure studies in New York and colon cancer risk (Callahan et al., 2017) as well as exposure to spouses of pesticide applicators in the US and rectal cancer risk (Alavanja et al., 2005), and New York state farm residents (Wang et al., 2002) and South Korean populations living near farms (Lee et al., 2008) with CRC risk.

3.3.3. Discussion of at-risk Populations’ Pesticide Exposure and Association with Colon Cancer, Rectal Cancer, and CRC Risk

Among occupational exposure studies, there were more significant inverse associations (27) than positive associations (11) with colon cancer, rectal cancer, and CRC risk reported. Similarly, among those exposed because of their environment there were 2 significant positive associations and 4 inverse associations with colon cancer, rectal cancer, or CRC risk. Overall, there were more significant inverse associations (31) than significant positive associations (13) reported between occupational or environmental pesticide exposure and colon cancer, rectal cancer, or CRC risk. Therefore, based on the direction of these trends and the strength of their association, we conclude that environmental and occupational pesticide exposure has an inverse association with colon cancer, rectal cancer, and CRC risk.

3.4. Comparison to Past Review Articles

As a part of our literature review, we have found nine review articles related to the effect of pesticide exposure on CRC risk (Acquavella et al., 1998; Alavanja and Bonner, 2012; Alexander et al., 2012; Blair and Freeman, 2009; Blair et al., 1985a; Blair et al., 1992; Burns, 2005; Oddone et al., 2014; Weichenthal et al., 2010). We have included all of the original research articles cited in these reviews related to the effect of pesticide exposure on CRC risk except for three which we did not have full text access (Gallagher et al., 1989; Schwartz and Grady, 1986; Wiklund, 1986). Overall, previous review papers have reported that there are no associations (Alexander et al., 2012) or inverse associations between occupational or environmental exposure to pesticides and CRC risk (Acquavella et al., 1998; Blair and Freeman, 2009; Blair et al., 1985a; Oddone et al., 2014). Previous review articles that have looked at the association between certain pesticides and colon or rectal cancer risk (Alavanja and Bonner, 2012; Alexander et al., 2012; Weichenthal et al., 2010) have reported significant positive associations with exposure to eleven pesticides and colon or rectal cancer risk including aldicarb (Lee et al., 2007b), dicamba (Samanic et al., 2006), EPTC (van Bemmel et al., 2008), imazethapyr (Koutros et al., 2009), trifluralin (Kang et al., 2008), fonofos (Lee et al., 2007b), chlordane (Purdue et al., 2007), chlorpyrifos (Lee et al., 2004a; Lee et al., 2007b), pendimethalin (Hou et al., 2006), toxaphene (Lee et al., 2007b), and carbaryl (Lee et al., 2007b). These review papers also reported only one significant inverse associations between 2,4-D exposure and colon cancer risk (Lee et al., 2007b).

This review is novel and comprehensive to include all epidemiological and biological sample measurement research studies to date analyzing the association between pesticide exposure and colon cancer, rectal cancer, or CRC risk. Previous reviews have been limited on one type of pesticide or a few research articles to make their conclusions related to CRC risk. Here we identified similar amounts of reports presenting significant positive associations (39) and significant inverse associations (41) of pesticide exposure with colon cancer, rectal cancer, or CRC risk. Among the studies analyzing the association between exposure to certain pesticides and colon cancer, rectal cancer, or CRC risk we have found more significant positive associations (26) than significant inverse associations (10). Among at-risk populations in the studies that looked at general pesticide exposure, similarly to previous reviews we have reported that there were more significant inverse associations (31) between pesticide exposure and colon cancer, rectal cancer, or CRC risk found than significant positive associations (13).

3.5. Limitations of this Systematic Review

Small sample size is one of the limitations for many of the studies reviewed, resulting in a higher effect size needed to reach sufficient statistical power. Additionally, exposure misclassifications, inability to control for, or lack of information on some confounders, and lack of validity of death certificates are other common limitations of these studies. The healthy workers effect and dichotomous questions inherently place limits on the exposure level of pesticides.

The other limitation of this review is that there were 3 studies relevant to this review for which full text was unavailable, and because of this, they were not included (Gallagher et al., 1989; Schwartz and Grady, 1986; Wiklund, 1986). Additionally, some of the studies only reported the effect sizes to one or no decimal points, some did not report a CI, and some did not report p-values or p-trends, which might lead to misinterpretation depending on the extent of significance that is unknown. Another limitation of this review is that it is only a systematic, qualitative review and not a meta-analysis or quantitative review. A qualitative review and not a quantitative review was completed because of the large variation in the effect size variables used in these 139 studies.

Most of the analyses discussed in this review were epidemiological studies analyzing the association between pesticide exposure and colon cancer, rectal cancer, or CRC risk (Tables 2–4, and 6). This is important, especially when studying different communities (near farms or rural vs. urban) or occupations (such as farmers, pesticide applicators, or manufacturers). However, causal relationship cannot be established based on different endpoints (RR, HR, OR, SIR, etc.) due to the cross-sectional nature of the study. Additionally, limitations on epidemiological methods such as recall bias from self-report surveys can result in exposure misclassification in studies such as these, along with a small sample size and number of cancer cases leading to lower statistical power. Some other limitations of epidemiological studies include selection bias from loss to follow-up, self-selection bias from more educated and generally healthier populations, and the fact that most studies did not measure actual pesticide levels in biological samples.

Only a few studies (four out of 139) reviewed used biological sample measurements to study the risk of CRC from the direct measurement of pesticides and pesticide metabolites levels in human samples (Abdallah et al., 2017; Abolhassani et al., 2019; Lee et al., 2018; Soliman et al., 1997) (Table 5). These studies are commonly combined with surveys to document the history of pesticide exposure and cancer risk confounders and therefore improve the accuracy and predictive power. However, the biological sample measurement studies reviewed all analyzed serum samples, and none have used stool, colon wash, colon tissue, or polyps, which are more relevant to the target sample to answer research questions on colon or rectal cancer. In addition, blood exposure studies are limited by analytical technique (gas chromatography, liquid chromatography, liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, or enzyme-linked immunosorbent assay) and the analytical technique used may affect the limit of detection, sensitivity, and accuracy. Therefore, the measurement of pesticides and their metabolites in these other types of biological samples, such as stool, would reflect the actual environment within those organ sites. Fecal samples that contain pesticides, metabolites, and microbes have gained more interest in the past decade and can be collected in a non-invasive way. Ultimately, biological sample measurement studies could be used to identify the time since last exposure based on half-lives of certain pesticides and to determine levels of unauthorized use of pesticides to understand the length of time these pesticides may linger in the human body.

4. Conclusions

As previously mentioned this is a systematic, qualitative review and not a quantitative, meta-analysis. Therefore, we have not used the reported results from these reviewed studies to calculate an overall quantitative conclusion. Based on this review, a general conclusion cannot be drawn from the associations between pesticide exposure and colon cancer, rectal cancer, or CRC risk due to similar numbers of significant positive (39) and inverse (41) associations reported. We were however able to determine which particular pesticides should be of higher concern and should be studied further with respect to colon cancer, rectal cancer, or CRC risk.

From this literature review, we ranked the pesticides into three groups based on the concern in regards to these types of cancers (low, moderate, and high concern). These rankings are based on the reported associations between pesticide exposure and risk of these types of cancers as well as their recent use in the US, whether they were detected on imported food to the US, and whether they are banned in the US. The pesticides that showed no significant association or only inverse association with colon cancer, rectal cancer, or CRC risk are of low concern. The pesticides that showed a significant positive association with colon cancer, rectal cancer, or CRC risk but have been banned in the US and other countries (fonofos, aldrin, toxaphene, and heptachlor) (Donley, 2019; PAN, 2020) (Table 1) are also of low concern. However, aldicarb and dieldrin, which showed significant positive association with CRC risk and have been banned in the US and other countries, are of moderate concern because dieldrin residues were detected on food products imported into the US as of 2018 (FDA, 2018) and aldicarb has been shown to be used in the US as recently as 2017 (USGS, 2017) (Table 1). The pesticides that have been reported to have both positive and inverse associations with colon cancer, rectal cancer, or CRC risk should be studied further and therefore are of moderate concern (DDT, lindane, 2,4-D, alachlor, chlordane). MCPA, which has been shown to have small positive associations with rectal cancer (when used concurrently with 2,4-D) and has not been banned in the US (Donley, 2019; PAN, 2020) (Table 1), is also of moderate concern. Terbufos, dicamba, trifluralin, EPTC, imazethapyr, chlorpyrifos, carbaryl, pendimethalin, and acetochlor are of high concern because not only have they been shown to have significant positive associations with colon cancer, rectal cancer, or CRC risk, but they also have not been banned in the US (Donley, 2019; PAN, 2020) (Table 1). Based on these results we believe that the pesticides of moderate and high concern should be studied further among larger and more diverse populations in order to provide more supporting evidence of their concern. If these pesticides are found to be positively associated with these types of cancer in these more diversely populated future studies then they should be evaluated and banned in the US as well.

When it comes to the type of pesticides, there does not seem to be any clear trends with respect to concern over colon cancer, rectal cancer, or CRC risk. The majority of OCIs studied have been banned because of their health concerns, and triazine pesticides have not been shown to have any significant associations. In the other pesticide groups studied (OPIs, carbamates, chlorophenoxy, anilides/ anilines, and other pesticides) there are pesticides of moderate to high concern in all groups studied.

Overall, this review demonstrates that certain pesticides are positively associated with colon cancer, rectal cancer, or CRC risk and that certain pesticides are of high concern in relation to these types of cancers. More epidemiological and biological sample measurement-based research is needed, especially analyzing the association between the exposure of pesticides that are not banned in the US or anywhere and their association with CRC risk. These future studies would provide more evidence to support potentially banning or restricting these pesticides in the future if they are found to be positively associated with CRC among a larger, more diverse population or in different regions or to inform at-risk communities about these associations. The association of pesticide exposure on the risk of these types of cancers should be studied on various populations such as urban residents, rural residents potentially living near farms, and those who may be exposed to these pesticides at their job (farmer, pesticide applicator, and manufacturing). These studies would show the differences in the effect size and 95% CI which would suggest the difference in the exposure and cancer risk.

More importantly, more biological sample measurement studies are needed to determine the amount of time the pesticides or their metabolites remain in the environment (plants, produce, soil, dust, and water) or bio specimen from the population (blood, urine, saliva, and stool). If they remain in the environment or body for a longer time than anticipated, they may be able to cause more harm, especially with regards to long-term diseases such as CRC and they may be able to still cause harm even though they have been banned. These biological sample measurement studies should also examine whether these pesticides or their metabolites can be detected in more appropriate sample types such as stool or colon wash for colon cancer, rectal cancer, and CRC risk-based studies. Metabolites in the stool could be directly related to colorectal health. Participants with a recent colonoscopy could be impactful to this type of research because the status of their current colorectal health would be known.

Highlights.

Health disparity among rural communities in relation to colorectal cancer
Colorectal cancer is associated with lifestyle, environment, and occupation
Systematic review on pesticide exposure effect on colorectal cancer risk
Specific pesticide exposures positively associated with colorectal cancer risk

Acknowledgements

We thank Richard Beger (Chief, Biomarkers and Alternative Models Branch, Division of Systems Biology, National Center for Toxicological Research) for his advice and insight into metabolomics and biological sample measurements. The project described was supported by the Arkansas Center for Health Disparities grant 5U54MD002329 through the National Institute of Minority Health and Health Disparities (NIMHD), National Institutes of Health (NIH). The content is the sole responsibility of the authors and does not necessarily represent the official views of the NIH.

Funding Support

The project described was supported by the Arkansas Center for Health Disparities (5U54MD002329) through the National Institute of Minority Health and Health Disparities, National Institutes of Health (NIH), and the University of Arkansas for Medical Sciences Center for Biomedical Research Excellence Host Response to Cancer Therapy studies (P20GM109005) funded by the National Institute of General Medical Sciences. The content is the sole responsibility of the authors and does not necessarily represent the official views of the NIH.

Abbreviations:

CRC: colorectal cancer
US: United States
MCPA: 2-methyl-4-chlorophenoxyacetic acid
DDT: dichlorodiphenyltrichloroethane
DDE: dichlorodiphenyldichloroethylene
HCB: hexachlorobenzene
2,4,5-TP: 2-(2,4,5-trichloropehnoxy) propionic acid
EPTC: S-ethyl dipropylthiocarbamate
2,4-D: 2,4-dichlorophenoxyacetic acid
PCP: pentachlorophenol
TCP: tetrachlorophenol
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
OR: Odds ratio
RR: relative risk/risk ratio
HR: hazard ratio
SIR: standardized incidence ratio
SMR: standardized mortality ratio
SRR: standardized risk ratio
PMR: proportionate mortality ratio
PCMR: proportionate cancer mortality ratio
MOR: mortality odds ratio
CI: confidence interval
PDF: portable document format
OCI: organochlorine insecticides
OPI: organophosphate insecticide
LED: Lifetime exposure days
IWLED: Intensity weighted lifetime exposure days
T1: Tertile 1
T2: Tertile 2
T3: Tertile 3
T3L: Tertile 3 lower
T3U: Tertile 3 upper
T4: Tertile 4
SD: standard deviation
SE: standard error
NIMHD: National Institute of Minority Health and Health Disparities
NIH: National Institutes of Health

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

CRediT Authorship Contribution Statement

Eryn K. Matich: Conceptualization, Methodology, Validation, Investigation, Data Curation, Visualization, Writing – original draft, Funding acquisition; Shelbie Stahr: Visualization for Figures 2–7, Revisions; Ping-Ching Hsu and L. Joseph Su: Conceptualization, Advising, Supervisions, Revisions; all authors: Writing – review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

‘t Mannetje, McLean D, Cheng S, Boffetta P, Colin D, Pearce N, 2005. Mortality in New Zealand workers exposed to phenoxy herbicides and dioxins. Occup Environ Med 62, 34–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
Abdallah MA, Zaky AH, Covaci A, 2017. Levels and profiles of organohalogenated contaminants in human blood from Egypt. Chemosphere 176, 266–272. [DOI] [PubMed] [Google Scholar]
Abolhassani M, Asadikaram G, Paydar P, Fallah H, Aghaee-Afshar M, Moazed V, Akbari H, Moghaddam SD, Moradi A, 2019. Organochlorine and organophosphorous pesticides may induce colorectal cancer; A case-control study. Ecotox Environ Safe 178, 168–177. [DOI] [PubMed] [Google Scholar]
Acquavella J, Olsen G, Cole P, Ireland B, Kaneene J, Schuman S, Holden L, 1998. Cancer among farmers: A meta-analysis. Annals of Epidemiology 8, 64–74. [DOI] [PubMed] [Google Scholar]
Acquavella JF, Delzell E, Cheng H, Lynch CF, Johnson G, 2004. Mortality and cancer incidence among alachlor manufacturing workers 1968–99. Occup Environ Med 61, 680–685. [DOI] [PMC free article] [PubMed] [Google Scholar]
Acquavella JF, Riordan SG, Anne M, Lynch CF, Collins JJ, Ireland BK, Heydens WF, 1996. Evaluation of mortality and cancer incidence among alachlor manufacturing workers. Environ Health Persp 104, 728–733. [DOI] [PMC free article] [PubMed] [Google Scholar]
ACS, 2019. Cancer Facts & Figures 2019 Atlanta, GA: American Cancer Society. [Google Scholar]
ACS, 2021. Cancer Facts & Figures 2021 Atlanta, GA: American Cancer Society. [Google Scholar]
Alavanja MCR, Bonner MR, 2012. Occupational Pesticide Exposures and Cancer Risk: A Review. J Toxicol Env Heal B 15, 238–263. [DOI] [PMC free article] [PubMed] [Google Scholar]
Alavanja MCR, Sandler DP, Lynch CF, Knott C, Lubin JH, Tarone R, Thomas K, Dosemeci M, Barker J, Hoppin JA, Blair A, 2005. Cancer incidence in the agricultural health study. Scand J Work Env Hea 31, 39–45. [PubMed] [Google Scholar]
Alberghini V, Luberto F, Gobba F, Morelli C, Gori E, Tomesani N, 1991. Mortality among male farmers licensed to use pesticides. Med Lav 82, 18–24. [PubMed] [Google Scholar]
Alexander DD, Weed DL, Mink PJ, Mitchell ME, 2012. A weight-of-evidence review of colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic studies. Int Arch Occ Env Hea 85, 715–745. [DOI] [PubMed] [Google Scholar]
Ambroise D, Moulin JJ, Squinazi F, Protois JC, Fontana JM, Wild P, 2005. Cancer mortality among municipal pest-control workers. Int Arch Occ Env Hea 78, 387–393. [DOI] [PubMed] [Google Scholar]
Amoateng-Adjepong Y, Sathiakumar N, Delzell E, Cole P, 1995. Mortality among Workers at a Pesticide Manufacturing Plant. J Occup Environ Med 37, 471–478. [DOI] [PubMed] [Google Scholar]
Andreotti G, Freeman LEB, Hou LF, Coble J, Rusiecki J, Hoppin JA, Silverman DT, Alavanja MCR, 2009. Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study Cohort. International Journal of Cancer 124, 2495–2500. [DOI] [PMC free article] [PubMed] [Google Scholar]
Asp S, Riihimaki V, Hernberg S, Pukkala E, 1994. Mortality and Cancer Morbidity of Finnish Chlorophenoxy Herbicide Applicators - an 18-Year Prospective Follow-Up. Am J Ind Med 26, 243–253. [DOI] [PubMed] [Google Scholar]
Atzmon I, Linn S, Richter E, Portnov BA, 2012. Cancer risks in the Druze Isifya Village: Reasons and RF/MW antennas. Pathophysiology 19, 21–28. [DOI] [PubMed] [Google Scholar]
Barbosa MO, Ribeiro AR, Pereira MFR, Silva AMT, 2016. Eco-friendly LC-MS/MS method for analysis of multi-class micropollutants in tap, fountain, and well water from northern Portugal. Analytical and Bioanalytical Chemistry 408, 8355–8367. [DOI] [PubMed] [Google Scholar]
Barry KH, Koutros S, Lubin JH, Coble JB, Barone-Adesi F, Freeman LEB, Sandler DP, Hoppin JA, Ma XM, Zheng TZ, Alavanja MCR, 2012. Methyl bromide exposure and cancer risk in the Agricultural Health Study. Cancer Cause Control 23, 807–818. [DOI] [PMC free article] [PubMed] [Google Scholar]
Baudry J, Assmann KE, Touvier M, 2018. Association of Frequency of Organic Food Consumption With Cancer Risk: Findings From the NutriNet-Sante Prospective Cohort Study (vol 178, pg 1597, 2018). Jama Internal Medicine 178, 1732–1732. [DOI] [PMC free article] [PubMed] [Google Scholar]
Beane Freeman LE, Bonner MR, Blair A, Hoppin JA, Sandler DP, Lubin JH, Dosemeci M, Lynch CF, Knott C, Alavanja MCR, 2005. Cancer incidence among male pesticide applicators in the agricultural health study cohort exposed to diazinon. American Journal of Epidemiology 162, 1070–1079. [DOI] [PubMed] [Google Scholar]
Beane Freeman LE, Rusiecki JA, Hoppin JA, Lubin JH, Koutros S, Andreotti G, Zahm SH, Hines CJ, Coble JB, Barone-Adesi F, Sloan J, Sandler DP, Blair A, Alavanja MCR, 2011. Atrazine and Cancer Incidence Among Pesticide Applicators in the Agricultural Health Study (1994–2007). Environ Health Persp 119, 1253–1259. [DOI] [PMC free article] [PubMed] [Google Scholar]
Beard J, Sladden T, Morgan G, Berry G, Brooks L, McMichael A, 2003. Health impacts of pesticide exposure in a cohort of outdoor workers. Environ Health Persp 111, 724–730. [DOI] [PMC free article] [PubMed] [Google Scholar]
Blair A, Dosemeci M, Heineman EF, 1993. Cancer and Other Causes of Death among Male and Female Farmers from 23 States. Am J Ind Med 23, 729–742. [DOI] [PubMed] [Google Scholar]
Blair A, Freeman LB, 2009. Epidemiologic Studies in Agricultural Populations: Observations and Future Directions. J Agromedicine 14, 125–131. [DOI] [PMC free article] [PubMed] [Google Scholar]
Blair A, Malker H, Cantor KP, Burmeister L, Wiklund K, 1985a. Cancer among Farmers - a Review. Scand J Work Env Hea 11, 397–407. [DOI] [PubMed] [Google Scholar]
Blair A, Sandler DP, Tarone R, Lubin J, Thomas K, Hoppin JA, Samanic C, Coble J, Kamel F, Knott C, Dosemeci M, Zahm SH, Lynch CF, Rothman N, Alavanja MCR, 2005. Mortality among participants in the agricultural health study. Annals of Epidemiology 15, 279–285. [DOI] [PubMed] [Google Scholar]
Blair A, Walrath J, Rogot E, 1985b. Mortality Patterns among United-States Veterans by Occupation .1. Cancer. Jnci-J Natl Cancer I 75, 1039–1047. [PubMed] [Google Scholar]
Blair A, Zahm SH, Pearce NE, Heineman EF, Fraumeni JF, 1992. Clues to Cancer Etiology from Studies of Farmers. Scand J Work Env Hea 18, 209–215. [DOI] [PubMed] [Google Scholar]
Bonner MR, Coble J, Blair A, Freeman LEB, Hoppin JA, Sandler DP, Alavanja MCR, 2007. Malathion exposure and the incidence of cancer in the agricultural health study. American Journal of Epidemiology 166, 1023–1034. [DOI] [PubMed] [Google Scholar]
Bonner MR, Lee WJ, Sandler DA, Hoppin JA, Dosemeci M, Alavanja MCR, 2005. Occupational exposure to carbofuran and the incidence of cancer in the Agricultural Health Study. Environ Health Persp 113, 285–289. [DOI] [PMC free article] [PubMed] [Google Scholar]
Bonner MR, Williams BA, Rusiecki JA, Blair A, Freeman LEB, Hoppin JA, Dosemeci M, Lubin J, Sandler DP, Alavanja MCR, 2010. Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study. Cancer Cause Control 21, 871–877. [DOI] [PMC free article] [PubMed] [Google Scholar]
Boyle T, Keegel T, Bull F, Heyworth J, Fritschi L, 2012. Physical Activity and Risks of Proximal and Distal Colon Cancers: A Systematic Review and Meta-analysis. Jnci-J Natl Cancer I 104, 1548–1561. [DOI] [PubMed] [Google Scholar]
Bradbury KE, Balkwill A, Spencer EA, Roddam AW, Reeves GK, Green J, Key TJ, Beral V, Pirie K, Collaborators MWS, 2014. Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom. Brit J Cancer 110, 2321–2326. [DOI] [PMC free article] [PubMed] [Google Scholar]
Brownson RC, Reif JS, Chang JC, Davis JR, 1989. Cancer Risks among Missouri Farmers. Cancer-Am Cancer Soc 64, 2381–2386. [DOI] [PubMed] [Google Scholar]
Bueno de Demesquita HB, Doornbos G, Vanderkuip DAM, Kogevinas M, Winkelmann R, 1993. Occupational Exposure to Phenoxy Herbicides and Chlorophenols and Cancer Mortality in the Netherlands. Am J Ind Med 23, 289–300. [DOI] [PubMed] [Google Scholar]
Bunch TR, Gervais JA, Buhl K, Stone D, 2012. Dicamba General Fact Sheet National Pesticide Information Center, Oregon State University Extension Services. http://npic.orst.edu/factsheets/dicamba_gen.html. [Google Scholar]
Burmeister LF, 1981. Cancer Mortality in Iowa Farmers, 1971–78. Jnci-J Natl Cancer I 66, 461–464. [PubMed] [Google Scholar]
Burns C, Bodner K, Swaen G, Collins J, Beard K, Lee M, 2011. Cancer Incidence of 2,4-D Production Workers. Int J Env Res Pub He 8, 3579–3590. [DOI] [PMC free article] [PubMed] [Google Scholar]
Burns CJ, 2005. Cancer among pesticide manufacturers and applicators. Scand J Work Env Hea 31, 9–17. [PubMed] [Google Scholar]
Burns CJ, Beard KK, Cartmill JB, 2001. Mortality in chemical workers potentially exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) 1945–94: an update. Occup Environ Med 58, 24–30. [DOI] [PMC free article] [PubMed] [Google Scholar]
Callahan CL, Vena JE, Green J, Swanson M, Mu LN, Bonner MR, 2017. Consumption of Lake Ontario sport fish and the incidence of colorectal cancer in the New York State Angler Cohort Study (NYSACS). Environ Res 154, 86–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
Cantor KP, Silberman W, 1999. Mortality among aerial pesticide applicators and flight instructors: Follow-up from 1965–1988. Am J Ind Med 36, 239–247. [DOI] [PubMed] [Google Scholar]
Carter BD, Abnet CC, Feskanich D, Freedman ND, Hartge P, Lewis CE, Ockene JK, Prentice RL, Speizer FE, Thun MJ, Jacobs EJ, 2015. Smoking and Mortality - Beyond Established Causes. New Engl J Med 372, 631–640. [DOI] [PubMed] [Google Scholar]
CDC, 1993. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Heptachlor/Heptachlor Epoxide U.S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 1993. [Google Scholar]
Christensen CH, Platz EA, Andreotti G, Blair A, Hoppin JA, Koutros S, Lynch CF, Sandler DA, Alavanja MCR, 2010. Coumaphos Exposure and Incident Cancer among Male Participants in the Agricultural Health Study (AHS). Environ Health Persp 118, 92–96. [DOI] [PMC free article] [PubMed] [Google Scholar]
Cocco P, Blair A, Congia P, Saba G, Flore C, Ecca MR, Palmas C, 1997. Proportional mortality of dichloro-diphenyl-trichloroethane (DDT) workers: A preliminary report. Arch Environ Health 52, 299–303. [DOI] [PubMed] [Google Scholar]
Coggon D, Pannett B, Winter PD, Acheson ED, Bonsall J, 1986. Mortality of Workers Exposed to 2 Methyl-4 Chlorophenoxyacetic Acid. Scand J Work Env Hea 12, 448–454. [DOI] [PubMed] [Google Scholar]
Cohen J, 1988. Statistical Power Analysis for the Behavioral-Sciences. Percept Motor Skill 67, 1007–1007. [Google Scholar]
Colt JS, Stallones L, Cameron LL, Dosemeci M, Zahm SH, 2001. Proportionate mortality among US migrant and seasonal farmworkers in twenty-four states. Am J Ind Med 40, 604–611. [DOI] [PubMed] [Google Scholar]
Cryder Z, Greenberg L, Richards J, Wolf D, Luo YZ, Gan J, 2019. Fiproles in urban surface runoff: Understanding sources and causes of contamination. Environ Pollut 250, 754–761. [DOI] [PMC free article] [PubMed] [Google Scholar]
De Roos AJ, Blair A, Rusiecki JA, Hoppin JA, Svec M, Dosemeci M, Sandler DP, Alavanja MC, 2005. Cancer incidence among glyphosate-exposed pesticide applicators in the agricultural health study. Environ Health Persp 113, 49–54. [DOI] [PMC free article] [PubMed] [Google Scholar]
Decoufle P, Stanislawczyk K, 1977. A retrospective survey of cancer in relation to occupation U.S. Dept. of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, Division of Surveillance, Hazard Evaluations for sale by the Supt. of Docs., U.S. Govt. Print. Off., Cincinnati, Washington. [Google Scholar]
Delancey JOL, Alavanja MCR, Coble J, Blair A, Hoppin JA, Austin HD, Freeman LEB, 2009. Occupational Exposure to Metribuzin and the Incidence of Cancer in the Agricultural Health Study. Annals of Epidemiology 19, 388–395. [DOI] [PMC free article] [PubMed] [Google Scholar]
Delzell E, Grufferman S, 1985. Mortality among White and Nonwhite Farmers in North-Carolina, 1976–1978. American Journal of Epidemiology 121, 391–402. [DOI] [PubMed] [Google Scholar]
Demers PA, Davies HW, Friesen MC, Hertzman C, Ostry A, Hershler R, Teschke K, 2006. Cancer and occupational exposure to pentachlorophenol and tetrachlorophenol (Canada). Cancer Cause Control 17, 749–758. [DOI] [PubMed] [Google Scholar]
Depczynski J, Dobbins T, Armstrong B, Lower T, 2018a. Comparison of cancer incidence in Australian farm residents 45 years and over, compared to rural non-farm and urban residents - a data linkage study. Bmc Cancer 18. [DOI] [PMC free article] [PubMed] [Google Scholar]
Depczynski J, Dobbins T, Armstrong B, Lower T, 2018b. Stage of diagnosis of prostate, breast and colorectal cancer in farm residents compared with other rural and urban residents in New South Wales. Aust J Rural Health 26, 56–62. [DOI] [PubMed] [Google Scholar]
Deziel NC, Freeman LEB, Hoppin JA, Thomas K, Lerro CC, Jones RR, Hines CJ, Blair A, Graubard BI, Lubin JH, Sandler DP, Chen HL, Andreotti G, Alavanja MC, Friesen MC, 2019. An algorithm for quantitatively estimating non-occupational pesticide exposure intensity for spouses in the Agricultural Health Study. J Expo Sci Env Epid 29, 344–357. [DOI] [PMC free article] [PubMed] [Google Scholar]
Ditraglia D, Brown DP, Namekata T, Iverson N, 1981. Mortality Study of Workers Employed at Organochlorine Pesticide Manufacturing Plants. Scand J Work Env Hea 7, 140–146. [PubMed] [Google Scholar]
Dodge JL, Mills PK, Riordan DG, 2007. Cancer survival in California Hispanic farmworkers, 1988–2001. J Rural Health 23, 33–41. [DOI] [PubMed] [Google Scholar]
Dong K, 2007. Insect sodium channels and insecticide resistance. Invert Neurosci 7, 17–30. [DOI] [PMC free article] [PubMed] [Google Scholar]
Donley N, 2019. The USA lags behind other agricultural nations in banning harmful pesticides. Environ Health-Glob 18. [DOI] [PMC free article] [PubMed] [Google Scholar]
Dornetshuber-Fleiss R, Heffeter P, Mohr T, Hazemi P, Kryeziu K, Seger C, Berger W, Lemmens-Gruber R, 2013. Destruxins: Fungal-derived cyclohexadepsipeptides with multifaceted anticancer and antiangiogenic activities. Biochemical Pharmacology 86, 361–377. [DOI] [PMC free article] [PubMed] [Google Scholar]
Dubrow R, Wegman DH, 1984. Occupational characteristics of cancer victims in Massachusetts 1971–1973 National Institute for Occupational Safety and Health, Cinncinnati, OH. (DHEW (NIOSH) publication no 84–109). [Google Scholar]
EPA, 1993. Butylate, R.E.D. Facts, Office of Prevention, Pesticides and Toxic Substances (7508W), EPA-738-F-93–014, U. S. Environmental Protection Agency, September 1993. . [Google Scholar]
EPA, 1994. Deposition of Air Pollutants to the Great Waters. First Report to Congress. EPA-453/R-93–055. Office of Air Quality Planning and Standards, Research Triangle Park, NC. U.S. Environmental Protection Agency, 1994. [Google Scholar]
EPA, 1996. Technical Factsheet on: TOXAPHENE. National Primary Drinking Water Regulations United States Environmental Protection Agency. [Google Scholar]
EPA, 1998. Reregistration Eligibility Decision (RED) for Alachlor; EPA 738-R-98–020, List A Case 0063, U.S [Google Scholar]
Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances (7508C), U.S. Government Printing Office: Washington, DC, 1998. [Google Scholar]
EPA, 1999. EPTC, R.E.D. Facts, Office of Prevention, Pesticides and Toxic Substances (7508W), EPA-738-F-99–011, U. S. Environmental Protection Agency, September 1999. . [Google Scholar]
EPA, 2002. Aldicarb (CASRN 116–06-3), Chemical Assessment Summary, Integrated Risk Information System (IRIS), National Center for Environmental Assessment, U. S. Environmental Protection Agency. . [Google Scholar]
EPA, 2004. Reregistration Eligibility Decision (RED) for MCPA (2-methyl-4-chlorophenoxyacetic acid); List A Case 0017, September 30, 2004, U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, U.S. Government Printing Office: Washington, DC, 2004. [Google Scholar]
EPA, 2005. Reregistration Eligibility Decision (RED) 2,4-D; EPA 738-R-05–002; U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, U.S. Government Printing Office: Washington, DC, 2005. [Google Scholar]
EPA, 2007. Pendimethalin. Human Health Risk Assessment for the Proposed Food Uses of the Herbicide, Memorandum, U. S. Environmental Protection Agency, Washington, DC, August 22, 2007. . [Google Scholar]
EPA, 2020. Basic Information about Pesticide Ingredients U.S. Environmental Protection Agency, January 21, 2020. [Google Scholar]
Faustini A, Forastiere F, Di Betta L, Magliola EM, Perucci CA, 1993. Cohort study of mortality among farmers and agricultural workers. Med Lav 84, 31–41. [PubMed] [Google Scholar]
FDA, 2018. Pesticide Reidue Monitoring Program Fiscal Year 2018 Pesticide Report, U.S. Food and Drug Administration, 2018. . [Google Scholar]
Figa-Talamanca I, Mearelli I, Valente P, Bascherini S, 1993. Cancer Mortality in a Cohort of Rural Licensed Pesticide Users in the Province of Rome. Int J Epidemiol 22, 579–583. [DOI] [PubMed] [Google Scholar]
Fincham SM, Hanson J, Berkel J, 1992. Patterns and Risks of Cancer in Farmers in Alberta. Cancer-Am Cancer Soc 69, 1276–1285. [DOI] [PubMed] [Google Scholar]
Fleming LE, Bean JA, Rudolph M, Hamilton K, 1999a. Cancer incidence in a cohort of licensed pesticide applicators in Florida. J Occup Environ Med 41, 279–288. [DOI] [PubMed] [Google Scholar]
Fleming LE, Bean JA, Rudolph M, Hamilton K, 1999b. Mortality in a cohort of licenced pesticide applicators in Florida. Occup Environ Med 56, 14–21. [DOI] [PMC free article] [PubMed] [Google Scholar]
Forastiere F, Quercia A, Miceli M, Settimi L, Terenzoni B, Rapiti E, Faustini A, Borgia P, Cavariani F, Perucci CA, 1993. Cancer among Farmers in Central Italy. Scand J Work Env Hea 19, 382–389. [DOI] [PubMed] [Google Scholar]
Fox AJ, Goldblatt PO, 1980. Longitudinal study of sociodemographic mortality differentials, 1971–1975, Office of Population Census and Surveys. Her Majesty’s Stationary Office, London. (Series LS no 1). [Google Scholar]
Fragar L, Depczynski J, Lower T, 2011. Mortality patterns of Australian male farmers and farm managers. Aust J Rural Health 19, 179–184. [DOI] [PubMed] [Google Scholar]
Franceschi S, Barbone F, Bidoli E, Guarneri S, Serraino D, Talamini R, La Vecchia C, 1993. Cancer risk in farmers: results from a multi-site case-control study in north-eastern Italy. Int J Cancer 53, 740–745. [DOI] [PubMed] [Google Scholar]
Fukuto TR, 1990. Mechanism of Action of Organophosphorus and Carbamate Insecticides. Environ Health Persp 87, 245–254. [DOI] [PMC free article] [PubMed] [Google Scholar]
Gallagher RP, Threlfall WJ, Band PR, 1989. Occupational Mortality diseases in occupations with potential exposure to phenoxyacetic acids in British Columbia 1950–84 Cancer Control Agency of British Columbia. [Google Scholar]
Gallagher RP, Threlfall WJ, Jeffries E, Band PR, Spinelli J, Coldman AJ, 1984. Cancer and Aplastic-Anemia in British-Columbia Farmers. J Natl Cancer I 72, 1311–1315. [PubMed] [Google Scholar]
Garabrant DH, Peters JM, Mack TM, Bernstein L, 1984. Job Activity and Colon Cancer Risk. American Journal of Epidemiology 119, 1005–1014. [DOI] [PubMed] [Google Scholar]
Greenburg DL, Rusiecki J, Koutros S, Dosemeci M, Patel R, Hines CJ, Hoppin JA, Alavanja MCR, 2008. Cancer incidence among pesticide applicators exposed to captan in the Agricultural Health Study. Cancer Cause Control 19, 1401–1407. [DOI] [PubMed] [Google Scholar]
Grossmann K, 2010. Auxin herbicides: current status of mechanism and mode of action. Pest Manag Sci 66, 113–120. [DOI] [PubMed] [Google Scholar]
Gunnarsdottir H, Rafnsson V, 1991. Cancer Incidence among Icelandic Farmers 1977–1987. Scand J Soc Med 19, 170–173. [DOI] [PubMed] [Google Scholar]
Guralnick L, 1963. Mortality by occupation and cause of death Department of Health, Education, and Welfare, Washington, DC; 1963. (Vital statistics speecial report 53(3), DHEW (PHS)). [Google Scholar]
Hall RCW, Hall RCW, 1999. Long-term psychological and neurological complications of lindane poisoning. Psychosomatics 40, 513–517. [DOI] [PubMed] [Google Scholar]
Harrahy E, 2003a. Multi-use Fact Sheet for Acetochlor: (Aquatic Life - acute concentration), Wisconsin Department of Natural Resources, 2003. [Google Scholar]
Harrahy E, 2003b. Multi-use Fact Sheet for Triflurlin: (Aquatic Life - acute concentration), Wisconsin Department of Natural Resources, 2003. [Google Scholar]
Helweg A, 1987. Degradation and Adsorption of C-14 Mcpa in Soil - Influence of Concentration, Temperature and Moisture-Content on Degradation. Weed Res 27, 287–296. [Google Scholar]
Hoar SK, Blair A, Holmes FF, Boysen C, Robel RJ, 1985. Herbicides and Colon Cancer. Lancet 1, 1277–1278. [DOI] [PubMed] [Google Scholar]
Holten R, Boe FN, Almvik M, Katuwal S, Stenrod M, Larsbo M, Jarvis N, Eklo OM, 2018. The effect of freezing and thawing on water flow and MCPA leaching in partially frozen soil. J Contam Hydrol 219, 72–85. [DOI] [PubMed] [Google Scholar]
Hou LF, Lee WJ, Rusiecki J, Hoppin JA, Blair A, Bonner MR, Lubin JH, Samanic C, Sandler DP, Dosemeci M, Alavanja MCR, 2006. Pendimethalin exposure and cancer incidence among pesticide applicators. Epidemiology 17, 302–307. [DOI] [PMC free article] [PubMed] [Google Scholar]
Howe GR, Lindsay JP, 1983. A follow-up study of a ten-percent sample of the Canadian labor force. I. Cancer mortality in males, 1965–73. J Natl Cancer Inst 70, 37–44. [PubMed] [Google Scholar]
Howsam M, Grimalt JO, Guino E, Navarro M, Marti-Rague J, Peinado MA, Capella G, Moreno V, Grp BCC, 2004. Organochlorine exposure and colorectal cancer risk. Environ Health Persp 112, 1460–1466. [DOI] [PMC free article] [PubMed] [Google Scholar]
HSDB, 1993. U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database) National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993. [Google Scholar]
Ilgaz A, Gozum S, 2018. Determination of Colorectal Cancer Risk Levels, Colorectal Cancer Screening Rates, and Factors Affecting Screening Participation of Individuals Working in Agriculture in Turkey. Cancer Nurs 41, E46–E54. [DOI] [PubMed] [Google Scholar]
Kachuri L, Harris MA, MacLeod JS, Tjepkema M, Peters PA, Demers PA, 2017. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC). Bmc Cancer 17. [DOI] [PMC free article] [PubMed] [Google Scholar]
Kaerlev L, Lynge E, Sabroe S, Olsen J, 2004. Colon cancer controls versus population controls in case-control studies of occupational risk factors. Bmc Cancer 4. [DOI] [PMC free article] [PubMed] [Google Scholar]
Kang D, Park SK, Beane-Freeman L, Lynch CF, Knott CE, Sandler DP, Hoppin JA, Dosemeci M, Coble J, Lubin J, Blair A, Alavanja M, 2008. Cancer incidence among pesticide applicators exposed to trifluralin in the Agricultural Health Study. Environ Res 107, 271–276. [DOI] [PMC free article] [PubMed] [Google Scholar]
Keller JE, Howe HL, 1994. Case-Control Studies of Cancer in Illinois Farmers Using Data from the Illinois-State-Cancer-Registry and the Us-Census-of-Agriculture. European Journal of Cancer 30a, 469–473. [DOI] [PubMed] [Google Scholar]
Kogevinas M, Becher H, Benn T, Bertazzi PA, Boffetta P, BuenodeMesquita HB, Coggon D, Colin D, FleschJanys D, Fingerhut M, Green L, Kauppinen T, Littorin M, Lynge E, Mathews JD, Neuberger M, Pearce N, Saracci R, 1997. Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins - An expanded and updated international cohort study. American Journal of Epidemiology 145, 1061–1075. [DOI] [PubMed] [Google Scholar]
Koutros S, Lynch CF, Ma XM, Lee WJ, Hoppin JA, Christensen CH, Andreotti G, Freeman LB, Rusiecki JA, Hou LF, Sandler DP, Alavanja MCR, 2009. Heterocyclic aromatic amine pesticide use and human cancer risk: Results from the US Agricultural Health Study. International Journal of Cancer 124, 1206–1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
Koutros S, Mahajan R, Zheng TZ, Hoppin JA, Ma XM, Lynch CF, Blair A, Alavanja MCR, 2008. Dichlorvos exposure and human cancer risk: results from the Agricultural Health Study. Cancer Cause Control 19, 59–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
Lee WJ, Alavania MCR, Hoppin JA, Rusiecki JA, Kamel F, Blair A, Sandler DP, 2007a. Mortality among pesticide applicators exposed to chlorpyrifos in the agricultural health study. Environ Health Persp 115, 528–534. [DOI] [PMC free article] [PubMed] [Google Scholar]
Lee WJ, Blair A, Hoppin JA, Lubin JH, Rusiecki JA, Sandler DP, Dosemeci M, Alavanja MCR, 2004a. Cancer incidence among pesticide applicators exposed to chlorpyrifos in the agricultural health study. Jnci-J Natl Cancer I 96, 1781–1789. [DOI] [PubMed] [Google Scholar]
Lee WJ, Hoppin JA, Blair A, Lubin JH, Dosemeci M, Sandler DP, Alavanja MCR, 2004b. Cancer incidence among pesticide applicators exposed to alachlor in the Agricultural Health Study. American Journal of Epidemiology 159, 373–380. [DOI] [PubMed] [Google Scholar]
Lee WJ, Sandler DP, Blair A, Samanic C, Cross AJ, Alavanja MCR, 2007b. Pesticide use and colorectal cancer risk in the Agricultural Health Study. International Journal of Cancer 121, 339–346. [DOI] [PMC free article] [PubMed] [Google Scholar]
Lee WJ, Son M, Chun BC, Park ES, Lee HK, Coble J, Dosemeci M, 2008. Cancer mortality and farming in South Korea: an ecologic study. Cancer Cause Control 19, 505–513. [DOI] [PubMed] [Google Scholar]
Lee YM, Kim SA, Choi GS, Park SY, Jeon SW, Lee HS, Lee SJ, Heo S, Lee DH, 2018. Association of colorectal polyps and cancer with low-dose persistent organic pollutants: A case-control study. Plos One 13. [DOI] [PMC free article] [PubMed] [Google Scholar]
Leet T, Acquavella J, Lynch C, Anne M, Weiss NS, Vaughan T, Checkoway H, 1996. Cancer incidence among alachlor manufacturing workers. Am J Ind Med 30, 300–306. [DOI] [PubMed] [Google Scholar]
Lerro CC, Koutros S, Andreotti G, Friesen MC, Alavanja MC, Blair A, Hoppin JA, Sandler DP, Lubin JH, Ma XM, Zhang YW, Freeman LEB, 2015a. Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study. Occup Environ Med 72, 736–744. [DOI] [PMC free article] [PubMed] [Google Scholar]
Lerro CC, Koutros S, Andreotti G, Hines CJ, Blair A, Lubin J, Ma XM, Zhang YW, Beane Freeman LE, 2015b. Use of acetochlor and cancer incidence in the Agricultural Health Study. International Journal of Cancer 137, 1167–1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
Limay-Rios V, Forero LG, Xue YG, Smith J, Baute T, Schaafsma A, 2016. Neonicotinoid insecticide residues in soil dust and associated parent soil in fields with a history of seed treatment use on crops in southwestern Ontario. Environ Toxicol Chem 35, 303–310. [DOI] [PubMed] [Google Scholar]
Littorin M, Attewell R, Skerfving S, Horstmann V, Moller T, 1993. Mortality and Tumor Morbidity among Swedish Market Gardeners and Orchardists. Int Arch Occ Env Hea 65, 163–169. [DOI] [PubMed] [Google Scholar]
Lo AC, Soliman AS, Khaled HM, Aboelyazid A, Greenson JK, 2010. Lifestyle, Occupational, and Reproductive Factors and Risk of Colorectal Cancer. Diseases of the Colon & Rectum 53, 830–837. [DOI] [PMC free article] [PubMed] [Google Scholar]
Louis LM, Lerro CC, Friesen MC, Andreotti G, Koutros S, Sandler DP, Blair A, Robson MG, Freeman LEB, 2017. A prospective study of cancer risk among Agricultural Health Study farm spouses associated with personal use of organochlorine insecticides. Environ Health-Glob 16. [DOI] [PMC free article] [PubMed] [Google Scholar]
Lynch SM, Mahajan R, Freeman LEB, Hoppin JA, Alavanja MCR, 2009. Cancer incidence among pesticide applicators exposed to butylate in the Agricultural Health Study (AHS). Environ Res 109, 860–868. [DOI] [PMC free article] [PubMed] [Google Scholar]
Lynch SM, Rusiecki JA, Blair A, Dosemeci M, Lubin J, Sandler D, Hoppin JA, Lynch CF, Alavanja MCR, 2006. Cancer incidence among pesticide applicators exposed to cyanazine in the agricultural health study. Environ Health Persp 114, 1248–1252. [DOI] [PMC free article] [PubMed] [Google Scholar]
Lynge E, 1998. Cancer incidence in Danish phenoxy herbicide workers, 1947–1993. Environ Health Persp 106, 683–688. [DOI] [PMC free article] [PubMed] [Google Scholar]
Ma Y, Yang W, Song M, Smith-Warner SA, Yang J, Li Y, Ma W, Hu Y, Ogino S, Hu FB, Wen D, Chan AT, Giovannucci EL, Zhang X, 2018. Type 2 diabetes and risk of colorectal cancer in two large U.S. prospective cohorts. Br J Cancer 119, 1436–1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
MacLennan PA, Delzell E, Sathiakumar N, Myers SL, Cheng H, Grizzle W, Chen VW, Wu XC, 2002. Cancer incidence among triazine herbicide manufacturing workers. J Occup Environ Med 44, 1048–1058. [DOI] [PubMed] [Google Scholar]
MacMahon B, Monson RR, Wang HH, Zheng TZ, 1988. A second follow-up of mortality in a cohort of pesticide applicators. J Occup Med 30, 429–432. [DOI] [PubMed] [Google Scholar]
Mahajan R, Blair A, Coble J, Lynch CF, Hoppin JA, Sandler DP, Alavanja MCR, 2007. Carbaryl exposure and incident cancer in the Agricultural Health Study. International Journal of Cancer 121, 1799–1805. [DOI] [PubMed] [Google Scholar]
Mahajan R, Blair A, Lynch CF, Schroeder P, Hoppin JA, Sandler DP, Alavanja MCR, 2006a. Fonofos exposure and cancer incidence in the Agricultural Health Study. Environ Health Persp 114, 1838–1842. [DOI] [PMC free article] [PubMed] [Google Scholar]
Mahajan R, Bonner MR, Hoppin JA, Alavanja MCR, 2006b. Phorate exposure and incidence of cancer in the agricultural health study. Environ Health Persp 114, 1205–1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
Martin FL, Martinez EZ, Stopper H, Garcia SB, Uyemura SA, Kannen V, 2018. Increased exposure to pesticides and colon cancer: Early evidence in Brazil. Chemosphere 209, 623–631. [DOI] [PubMed] [Google Scholar]
McMichael AJ, Hartshorne JM, 1982. Mortality Risks in Australian Men by Occupational Groups, 1968–1978 Variations Associated with Differences in Drinking and Smoking-Habits. Med J Australia 1, 253–256. [PubMed] [Google Scholar]
McNabb S, Harrison TA, Albanes D, Berndt SI, Brenner H, Caan BJ, Campbell PT, Cao Y, Chang-Claude J, Chan A, Chen Z, English DR, Giles GG, Giovannucci EL, Goodman PJ, Hayes RB, Hoffmeister M, Jacobs EJ, Joshi AD, Larsson SC, Le Marchand L, Li L, Lin Y, Mannisto S, Milne RL, Nan H, Newton CC, Ogino S, Parfrey PS, Petersen PS, Potter JD, Schoen RE, Slattery ML, Su YR, Tangen CM, Tucker TC, Weinstein SJ, White E, Wolk A, Woods MO, Phipps AI, Peters U, 2020. Meta-analysis of 16 studies of the association of alcohol with colorectal cancer. Int J Cancer 146, 861–873. [DOI] [PMC free article] [PubMed] [Google Scholar]
Milham SJ, 1983. Occupational mortality in Washington State, 1950–1979 National Institute for Occupational Safety and Health, Cinncinnati, OH. (DHHS publication no (NIOSH) 83–116). [Google Scholar]
Mills PK, Kwong S, 2001. Cancer incidence in the united farmworkers of America (UFW), 1987–1997. Am J Ind Med 40, 596–603. [DOI] [PubMed] [Google Scholar]
Moher D, Liberati A, Tetzlaff J, Altman DG, Grp P, 2009. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Plos Medicine 6. [PMC free article] [PubMed] [Google Scholar]
Mozzachio AM, Rusiecki JA, Hoppin JA, Mahajan R, Patel R, Beane-Freeman L, Alavanja MCR, 2008. Chlorothalonil exposure and cancer incidence among pesticide applicator participants in the agricultural health study. Environ Res 108, 400–403. [DOI] [PMC free article] [PubMed] [Google Scholar]
Murillo G, Kosmeder JW, Pezzuro JM, Mehta RG, 2003. Deguelin suppresses the formation of carcinogen-induced aberrant crypt foci in the colon of CF-1 mice. International Journal of Cancer 104, 7–11. [DOI] [PubMed] [Google Scholar]
Murillo G, Salti GI, Kosmeder JW, Pezzuto JM, Mehta RG, 2002. Deguelin inhibits the growth of colon cancer cells through the induction of apoptosis and cell cycle arrest. European Journal of Cancer 38, 2446–2454. [DOI] [PubMed] [Google Scholar]
Narahashi T, 2002. Nerve Membrane Ion Channels as the Target Site of Insecticides. Mini-Rev Med Chem 2, 419–432. [DOI] [PubMed] [Google Scholar]
Nasterlack M, Hoffmann G, Messerer P, Ott MG, Pallapies D, Wrede M, Zober A, 2007. Epidemiological and clinical investigations among employees in a former herbicide production process. Int Arch Occ Env Hea 80, 234–238. [DOI] [PubMed] [Google Scholar]
NPIC, 2008. 2,4-D Technical Fact Sheet, National Pesticide Information Center, Oregon State University and U. S. Environmental Protection Agency, 2008. [Google Scholar]
Oddone E, Modonesi C, Gatta G, 2014. Occupational exposures and colorectal cancers: A quantitative overview of epidemiological evidence. World J Gastroentero 20, 12431–12444. [DOI] [PMC free article] [PubMed] [Google Scholar]
Olsen JH, Jensen OM, 1987. Occupation and Risk of Cancer in Denmark - an Analysis of 93810 Cancer Cases, 1970–1979 - Preface. Scand J Work Env Hea 13, 1-+. [PubMed] [Google Scholar]
PAN, 2020. Consolidated List of Banned Pesticides, Pesticide Action Network. [Google Scholar]
Park SK, Kang D, Beane-Freeman L, Blair A, Hoppin JA, Sandler DP, Lynch CF, Knott C, Gwak J, Alavanja M, 2009. Cancer Incidence Among Paraquat Exposed Applicators in the Agricultural Health Study Prospective Cohort Study. Int J Occup Env Heal 15, 274–281. [DOI] [PMC free article] [PubMed] [Google Scholar]
Parron T, Requena M, Hernandez AF, Alarcon R, 2014. Environmental exposure to pesticides and cancer risk in multiple human organ systems. Toxicol Lett 230, 157–165. [DOI] [PubMed] [Google Scholar]
Peterson GR, Milham SJ, 1980. Occupational mortality in the state of California, 1959–1961 National Institute for Occupational Safety and Health, Rockville, MD. (DHEW publication no (NIOSH, NIH) 80–104). [Google Scholar]
Powis G, Gallegos A, Abraham RT, Ashendel CL, Zalkow LH, Dorr R, Dvorakova K, Salmon S, Harrison S, Worzalla J, 1997. Inhibition of intracellular Ca2+ signalling, cytotoxicity and antitumor activity of the herbicide oryzalin and its analogues. Cancer Chemoth Pharm 41, 22–28. [DOI] [PubMed] [Google Scholar]
Purdue MP, Hoppin JA, Blair A, Dosemeci M, Alavanja MCR, 2007. Occupational exposure to organochlorine insecticides and cancer incidence in the Agricultural Health Study. International Journal of Cancer 120, 642–649. [DOI] [PMC free article] [PubMed] [Google Scholar]
Rafnsson V, 2006. Cancer incidence among farmers exposed to lindane while sheep dipping. Scand J Work Env Hea 32, 185–189. [DOI] [PubMed] [Google Scholar]
Rafnsson V, Gunnarsdottir H, 1989. Mortality among Farmers in Iceland. Int J Epidemiol 18, 146–151. [DOI] [PubMed] [Google Scholar]
Reif J, Pearce N, Fraser J, 1989. Cancer Risks in New-Zealand Farmers. Int J Epidemiol 18, 768–774. [DOI] [PubMed] [Google Scholar]
Ronco G, Costa G, Lynge E, 1992. Cancer Risk among Danish and Italian Farmers. Brit J Ind Med 49, 220–225. [DOI] [PMC free article] [PubMed] [Google Scholar]
Rusiecki JA, De Roos A, Lee WJ, Dosemeci M, Lubin JH, Hoppin JA, Blair A, Alavanja MCR, 2004. Cancer incidence among pesticide applicators exposed to atrazine in the agricultural health study. Jnci-J Natl Cancer I 96, 1375–1382. [DOI] [PubMed] [Google Scholar]
Rusiecki JA, Hou LF, Lee WJ, Blair A, Dosemeci M, Lubin JH, Bonner M, Samanic C, Hoppin JA, Sandler DP, Alavanja MCR, 2006. Cancer incidence among pesticide applicators exposed to metolachlor in the Agricultural Health Study. International Journal of Cancer 118, 3118–3123. [DOI] [PubMed] [Google Scholar]
Rusiecki JA, Patel R, Koutros S, Beane-Freeman L, Landgren O, Bonner MR, Coble J, Lubin J, Blair A, Hoppin JA, Alavanja MCR, 2009. Cancer Incidence among Pesticide Applicators Exposed to Permethrin in the Agricultural Health Study. Environ Health Persp 117, 581–586. [DOI] [PMC free article] [PubMed] [Google Scholar]
Saftlas AF, Blair A, Cantor KP, Hanrahan L, Anderson HA, 1987. Cancer and Other Causes of Death among Wisconsin Farmers. Am J Ind Med 11, 119–129. [DOI] [PubMed] [Google Scholar]
Salerno C, Carcagni A, Sacco S, Palin LA, Vanhaecht K, Panella M, Guido D, 2016. An Italian population-based case-control study on the association between farming and cancer: Are pesticides a plausible risk factor? Arch Environ Occup H 71, 147–156. [DOI] [PubMed] [Google Scholar]
Samanic C, Rusiecki J, Dosemeci M, Hou L, Hoppin JA, Sandler DP, Lubin J, Blair A, Alavanja MCR, 2006. Cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study. Environ Health Persp 114, 1521–1526. [DOI] [PMC free article] [PubMed] [Google Scholar]
Sathiakumar N, Delzell E, Cole P, 1996. Mortality among workers at two triazine herbicide manufacturing plants. Am J Ind Med 29, 143–151. [DOI] [PubMed] [Google Scholar]
Schreinemachers DM, 2000. Cancer mortality in four northern wheat-producing states. Environ Health Persp 108, 873–881. [DOI] [PMC free article] [PubMed] [Google Scholar]
Schwartz E, Grady K, 1986. Patterns of occupationalmortality in New Hampshire 1975–1985 Concord, NH: New Hampshire Division of Public Health Services. [Google Scholar]
Senseman SA, 2007. Herbicide Handbook, Ninth Edition Weed Sci. Soc. Am. Champaign, IL: 458 pp. 2007. [Google Scholar]
Settimi L, Comba P, Bosia S, Ciapini C, Desideri E, Fedi A, Perazzo PL, Axelson O, 2001. Cancer risk among male farmers: a multi-site case-control study. Int J Occup Med Environ Health 14, 339–347. [PubMed] [Google Scholar]
Sjerps RMA, Kooij PJF, van Loon A, Van Wezel AP, 2019. Occurrence of pesticides in Dutch drinking water sources. Chemosphere 235, 510–518. [DOI] [PubMed] [Google Scholar]
Soliman AS, Smith MA, Cooper SP, Ismail K, Khaled H, Ismail S, McPherson RS, Seifeldin IA, Bondy ML, 1997. Serum organochlorine pesticide levels in patients with colorectal cancer in Egypt. Arch Environ Health 52, 409–415. [DOI] [PubMed] [Google Scholar]
Stark AD, Chang HG, Fitzgerald EF, Riccardi K, Stone RR, 1987. A Retrospective Cohort Study of Mortality among New-York-State Farm Bureau Members. Arch Environ Health 42, 204–212. [PubMed] [Google Scholar]
Su F-C, Goutman SA, Chernyak S, Mukherjee B, Callaghan BC, Batterman S, Feldman EL, 2016. The Role of Environmental Toxins on ALS: A Case-Control Study of Occupational Risk Factors. JAMA Neurol 73, 803–811. [DOI] [PMC free article] [PubMed] [Google Scholar]
Sultana T, Murray C, Kleywegt S, Metcalfe CD, 2018. Neonicotinoid pesticides in drinking water in agricultural regions of southern Ontario, Canada. Chemosphere 202, 506–513. [DOI] [PubMed] [Google Scholar]
Sunol C, Tusell JM, Gelpi E, Rodriguezfarre E, 1989. Gabaergic Modulation of Lindane (Gamma-Hexachlorocyclohexane)-Induced Seizures. Toxicol Appl Pharm 100, 1–8. [DOI] [PubMed] [Google Scholar]
Swaen GMH, de Jong G, Slangen JJM, van Amelsvoort LG, 2002. Cancer mortality in workers exposed to dieldrin and aldrin: an update. Toxicol Ind Health 18, 63–70. [DOI] [PubMed] [Google Scholar]
Swaen GMH, van Amelsvoort LGPM, Slangen JJM, Mohren DCL, 2004. Cancer mortality in a cohort of licensed herbicide applicators. Int Arch Occ Env Hea 77, 293–295. [DOI] [PubMed] [Google Scholar]
Swaen GMH, Vanvliet C, Slangen JJM, Sturmans F, 1992. Cancer Mortality among Licensed Herbicide Applicators. Scand J Work Env Hea 18, 201–204. [DOI] [PubMed] [Google Scholar]
Sweden S, 1981. Dodsfalls registret 1961–1970 Stockholm. [Google Scholar]
Tan Z, Zhou J, Chen H, Zou Q, Weng S, Luo T, Tang Y, 2016. Toxic effects of 2,4-dichlorophenoxyacetic acid on human sperm function in vitro. J Toxicol Sci 41, 543–549. [DOI] [PubMed] [Google Scholar]
Torchio P, Lepore AR, Corrao G, Comba P, Settimi L, Belli S, Magnani C, Diorio F, 1994. Mortality Study on a Cohort of Italian Licensed Pesticide Users. Science of the Total Environment 149, 183–191. [DOI] [PubMed] [Google Scholar]
Une H, Schuman SH, Caldwell ST, Whitlock NH, 1987. Agricultural Life-Style - a Mortality Study among Male Farmers in South-Carolina, 1983–1984. South Med J 80, 1137–1140. [PubMed] [Google Scholar]
USGS, 2017. Pesticide National Synthesis Project, Estimated Annual Agricultural Pesticide Use, Archived preliminary county level pesticide use estimates, United States Geological Survey. [Google Scholar]
Uysal M, Bozcuk H, Karakilinc H, Goksu S, Tatli AM, Gunduz S, Arslan D, Coskun HS, Savas B, 2013. Pesticides and Cancer: The First Incidence Study Conducted in Turkey. J Environ Pathol Tox 32, 245–249. [DOI] [PubMed] [Google Scholar]
van Amelsvoort LGPM, Slangen JJM, Tsai SP, de Jong G, Kant I, 2009. Cancer mortality in workers exposed to dieldrin and aldrin: over 50 years of follow up. Int Arch Occ Env Hea 82, 217–225. [DOI] [PubMed] [Google Scholar]
van Bemmel DM, Visvanathan K, Freeman LEB, Coble J, Hoppin JA, Alavanja MCR, 2008. S-Ethyl-N,N-dipropylthiocarbamate Exposure and Cancer Incidence among Male Pesticide Applicators in the Agricultural Health Study: A Prospective Cohort. Environ Health Persp 116, 1541–1546. [DOI] [PMC free article] [PubMed] [Google Scholar]
Versluys JJ, 1949. Cancer and Occupation in the Netherlands. Brit J Cancer 3, 161–185. [DOI] [PMC free article] [PubMed] [Google Scholar]
Vieira AR, Abar L, Chan DSM, Vingeliene S, Polemiti E, Stevens C, Greenwood D, Norat T, 2017. Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project. Annals of Oncology 28, 1788–1802. [DOI] [PubMed] [Google Scholar]
Wales CTK, Taylor FR, Higa AT, McAllister HA, Jacobs AT, 2015. ERK-dependent phosphorylation of HSF1 mediates chemotherapeutic resistance to benzimidazole carbamates in colorectal cancer cells. Anti-Cancer Drug 26, 657–666. [DOI] [PubMed] [Google Scholar]
Walrath JJ, Rogot E, Murray J, Blair A, 1985. Mortality patterns among US veterans by occupation and smoking status US Government Printing Office, Washington, DC. (NIH publication no 85–2756). [Google Scholar]
Wang HH, Macmahon B, 1979. Mortality of Workers Employed in the Manufacture of Chlordane and Heptachlor. J Occup Environ Med 21, 745–748. [DOI] [PubMed] [Google Scholar]
Wang Y, Hwang SA, Lewis-Michl EL, Fitzgerald EF, Stark AD, 2003. Mortality among a cohort of female farm residents in New York State. Arch Environ Health 58, 642–648. [DOI] [PubMed] [Google Scholar]
Wang Y, Lewis-Michl EL, Hwang SA, Fitzgerald EF, Stark AD, 2002. Cancer incidence among a cohort of female farm residents in New York State. Arch Environ Health 57, 561–567. [DOI] [PubMed] [Google Scholar]
Weichenthal S, Moase C, Chan P, 2010. A Review of Pesticide Exposure and Cancer Incidence in the Agricultural Health Study Cohort. Environ Health Persp 118, 1117–1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
Weichenthal S, Moase C, Chan P, 2012. A Review of Pesticide Exposure and Cancer Incidence in the Agricultural Health Study Cohort. Cienc Saude Coletiva 17, 255–270. [DOI] [PubMed] [Google Scholar]
Wesseling C, Antich D, Hogstedt C, Rodriguez AC, Ahlbom A, 1999. Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure. Int J Epidemiol 28, 365–374. [DOI] [PubMed] [Google Scholar]
WHO, 2019. Recommended Classification of Pesticides by Hazard and Guidelines to Classification, World Health Organization. [Google Scholar]
WHO, 2020. International Agency for Research on Cancer Monographs on the Identification of Carcinogenic Hazards to Humans, World Health Organization, 2020. [Google Scholar]
Wiklund K, 1986. Cancer risks among agricultural workers in Sweden. Cohort studies based on Swedish cancer-environment register Karolinska hospital, Stockholm. [Google Scholar]
Wiklund K, Dich J, 1994. Cancer Risks among Female Farmers in Sweden. Cancer Cause Control 5, 449–457. [DOI] [PubMed] [Google Scholar]
Wiklund K, Dich J, Holm LE, Eklund G, 1989. Risk of Cancer in Pesticide Applicators in Swedish Agriculture. Brit J Ind Med 46, 809–814. [DOI] [PMC free article] [PubMed] [Google Scholar]
Wiklund K, Einhorn J, Wennstrom G, 1981. A Swedish Cancer-Environment Register Available for Research. Scand J Work Env Hea 7, 64–67. [DOI] [PubMed] [Google Scholar]
Wilkinson P, Thakrar B, Shaddick G, Stevenson S, Pattenden S, Landon M, Grundy C, Elliott P, 1997. Cancer incidence and mortality around the Pan Britannica Industries pesticide factory, Waltham Abbey. Occup Environ Med 54, 101–107. [DOI] [PMC free article] [PubMed] [Google Scholar]
Williams RR, Stegens NL, Goldsmith JR, 1977. Associations of cancer site and type with occupation and industry from the Third National Cancer Survey Interview. J Natl Cancer Inst 59, 1147–1185. [DOI] [PubMed] [Google Scholar]
Wong O, Brocker W, Davis HV, Nagle GS, 1984. Mortality of Workers Potentially Exposed to Organic and Inorganic Brominated Chemicals, Dbcp, Tris, Pbb, and Ddt. Brit J Ind Med 41, 15–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
Xu C, Chen L, You LH, Xu Z, Ren LF, Gin KYH, He YL, Kai WZ, 2018. Occurrence, impact variables and potential risk of PPCPs and pesticides in a drinking water reservoir and related drinking water treatment plants in the Yangtze Estuary. Environ Sci-Proc Imp 20, 1030–1045. [DOI] [PubMed] [Google Scholar]
Xue K, Li FF, Chen YW, Zhou YH, He J, 2017. Body mass index and the risk of cancer in women compared with men: a meta-analysis of prospective cohort studies. European Journal of Cancer Prevention 26, 94–105. [DOI] [PubMed] [Google Scholar]
Yi SW, 2013. Cancer incidence in Korean Vietnam veterans during 1992–2003: the Korean veterans health study. J Prev Med Public Health 46, 309–318. [DOI] [PMC free article] [PubMed] [Google Scholar]
Yi SW, Ohrr H, Hong JS, Yi JJ, 2013. Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans. J Prev Med Public Health 46, 213–225. [DOI] [PMC free article] [PubMed] [Google Scholar]
Yi SW, Ryu SY, Ohrr H, Hong JS, 2014. Agent Orange exposure and risk of death in Korean Vietnam veterans: Korean Veterans Health Study. Int J Epidemiol 43, 1825–1834. [DOI] [PubMed] [Google Scholar]
Yoshitani SI, Tanaka T, Kohno H, Takashima S, 2001. Chemoprevention of azoxymethane-induced rat colon carcinogenesis by dietary capsaicin and rotenone. Int J Oncol 19, 929–939. [DOI] [PubMed] [Google Scholar]
Zahm SH, 1997. Mortality study of pesticide applicators and other employees of a lawn care service company. J Occup Environ Med 39, 1055–1067. [DOI] [PubMed] [Google Scholar]
Zhong Y, Rafnsson V, 1996. Cancer incidence among Icelandic pesticide users. Int J Epidemiol 25, 1117–1124. [DOI] [PubMed] [Google Scholar]
Zhou Y, Liu JQ, Zhou ZH, Lv XT, Chen YQ, Sun LQ, Chen FX, 2016. Enhancement of CD3AK cell proliferation and killing ability by alpha-Thujone. Int Immunopharmacol 30, 57–61. [DOI] [PubMed] [Google Scholar]

[R1] ‘t Mannetje, McLean D, Cheng S, Boffetta P, Colin D, Pearce N, 2005. Mortality in New Zealand workers exposed to phenoxy herbicides and dioxins. Occup Environ Med 62, 34–40. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R2] Abdallah MA, Zaky AH, Covaci A, 2017. Levels and profiles of organohalogenated contaminants in human blood from Egypt. Chemosphere 176, 266–272. [DOI] [PubMed] [Google Scholar]

[R3] Abolhassani M, Asadikaram G, Paydar P, Fallah H, Aghaee-Afshar M, Moazed V, Akbari H, Moghaddam SD, Moradi A, 2019. Organochlorine and organophosphorous pesticides may induce colorectal cancer; A case-control study. Ecotox Environ Safe 178, 168–177. [DOI] [PubMed] [Google Scholar]

[R4] Acquavella J, Olsen G, Cole P, Ireland B, Kaneene J, Schuman S, Holden L, 1998. Cancer among farmers: A meta-analysis. Annals of Epidemiology 8, 64–74. [DOI] [PubMed] [Google Scholar]

[R5] Acquavella JF, Delzell E, Cheng H, Lynch CF, Johnson G, 2004. Mortality and cancer incidence among alachlor manufacturing workers 1968–99. Occup Environ Med 61, 680–685. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R6] Acquavella JF, Riordan SG, Anne M, Lynch CF, Collins JJ, Ireland BK, Heydens WF, 1996. Evaluation of mortality and cancer incidence among alachlor manufacturing workers. Environ Health Persp 104, 728–733. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R7] ACS, 2019. Cancer Facts & Figures 2019 Atlanta, GA: American Cancer Society. [Google Scholar]

[R8] ACS, 2021. Cancer Facts & Figures 2021 Atlanta, GA: American Cancer Society. [Google Scholar]

[R9] Alavanja MCR, Bonner MR, 2012. Occupational Pesticide Exposures and Cancer Risk: A Review. J Toxicol Env Heal B 15, 238–263. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R10] Alavanja MCR, Sandler DP, Lynch CF, Knott C, Lubin JH, Tarone R, Thomas K, Dosemeci M, Barker J, Hoppin JA, Blair A, 2005. Cancer incidence in the agricultural health study. Scand J Work Env Hea 31, 39–45. [PubMed] [Google Scholar]

[R11] Alberghini V, Luberto F, Gobba F, Morelli C, Gori E, Tomesani N, 1991. Mortality among male farmers licensed to use pesticides. Med Lav 82, 18–24. [PubMed] [Google Scholar]

[R12] Alexander DD, Weed DL, Mink PJ, Mitchell ME, 2012. A weight-of-evidence review of colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic studies. Int Arch Occ Env Hea 85, 715–745. [DOI] [PubMed] [Google Scholar]

[R13] Ambroise D, Moulin JJ, Squinazi F, Protois JC, Fontana JM, Wild P, 2005. Cancer mortality among municipal pest-control workers. Int Arch Occ Env Hea 78, 387–393. [DOI] [PubMed] [Google Scholar]

[R14] Amoateng-Adjepong Y, Sathiakumar N, Delzell E, Cole P, 1995. Mortality among Workers at a Pesticide Manufacturing Plant. J Occup Environ Med 37, 471–478. [DOI] [PubMed] [Google Scholar]

[R15] Andreotti G, Freeman LEB, Hou LF, Coble J, Rusiecki J, Hoppin JA, Silverman DT, Alavanja MCR, 2009. Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study Cohort. International Journal of Cancer 124, 2495–2500. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R16] Asp S, Riihimaki V, Hernberg S, Pukkala E, 1994. Mortality and Cancer Morbidity of Finnish Chlorophenoxy Herbicide Applicators - an 18-Year Prospective Follow-Up. Am J Ind Med 26, 243–253. [DOI] [PubMed] [Google Scholar]

[R17] Atzmon I, Linn S, Richter E, Portnov BA, 2012. Cancer risks in the Druze Isifya Village: Reasons and RF/MW antennas. Pathophysiology 19, 21–28. [DOI] [PubMed] [Google Scholar]

[R18] Barbosa MO, Ribeiro AR, Pereira MFR, Silva AMT, 2016. Eco-friendly LC-MS/MS method for analysis of multi-class micropollutants in tap, fountain, and well water from northern Portugal. Analytical and Bioanalytical Chemistry 408, 8355–8367. [DOI] [PubMed] [Google Scholar]

[R19] Barry KH, Koutros S, Lubin JH, Coble JB, Barone-Adesi F, Freeman LEB, Sandler DP, Hoppin JA, Ma XM, Zheng TZ, Alavanja MCR, 2012. Methyl bromide exposure and cancer risk in the Agricultural Health Study. Cancer Cause Control 23, 807–818. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R20] Baudry J, Assmann KE, Touvier M, 2018. Association of Frequency of Organic Food Consumption With Cancer Risk: Findings From the NutriNet-Sante Prospective Cohort Study (vol 178, pg 1597, 2018). Jama Internal Medicine 178, 1732–1732. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R21] Beane Freeman LE, Bonner MR, Blair A, Hoppin JA, Sandler DP, Lubin JH, Dosemeci M, Lynch CF, Knott C, Alavanja MCR, 2005. Cancer incidence among male pesticide applicators in the agricultural health study cohort exposed to diazinon. American Journal of Epidemiology 162, 1070–1079. [DOI] [PubMed] [Google Scholar]

[R22] Beane Freeman LE, Rusiecki JA, Hoppin JA, Lubin JH, Koutros S, Andreotti G, Zahm SH, Hines CJ, Coble JB, Barone-Adesi F, Sloan J, Sandler DP, Blair A, Alavanja MCR, 2011. Atrazine and Cancer Incidence Among Pesticide Applicators in the Agricultural Health Study (1994–2007). Environ Health Persp 119, 1253–1259. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R23] Beard J, Sladden T, Morgan G, Berry G, Brooks L, McMichael A, 2003. Health impacts of pesticide exposure in a cohort of outdoor workers. Environ Health Persp 111, 724–730. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R24] Blair A, Dosemeci M, Heineman EF, 1993. Cancer and Other Causes of Death among Male and Female Farmers from 23 States. Am J Ind Med 23, 729–742. [DOI] [PubMed] [Google Scholar]

[R25] Blair A, Freeman LB, 2009. Epidemiologic Studies in Agricultural Populations: Observations and Future Directions. J Agromedicine 14, 125–131. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R26] Blair A, Malker H, Cantor KP, Burmeister L, Wiklund K, 1985a. Cancer among Farmers - a Review. Scand J Work Env Hea 11, 397–407. [DOI] [PubMed] [Google Scholar]

[R27] Blair A, Sandler DP, Tarone R, Lubin J, Thomas K, Hoppin JA, Samanic C, Coble J, Kamel F, Knott C, Dosemeci M, Zahm SH, Lynch CF, Rothman N, Alavanja MCR, 2005. Mortality among participants in the agricultural health study. Annals of Epidemiology 15, 279–285. [DOI] [PubMed] [Google Scholar]

[R28] Blair A, Walrath J, Rogot E, 1985b. Mortality Patterns among United-States Veterans by Occupation .1. Cancer. Jnci-J Natl Cancer I 75, 1039–1047. [PubMed] [Google Scholar]

[R29] Blair A, Zahm SH, Pearce NE, Heineman EF, Fraumeni JF, 1992. Clues to Cancer Etiology from Studies of Farmers. Scand J Work Env Hea 18, 209–215. [DOI] [PubMed] [Google Scholar]

[R30] Bonner MR, Coble J, Blair A, Freeman LEB, Hoppin JA, Sandler DP, Alavanja MCR, 2007. Malathion exposure and the incidence of cancer in the agricultural health study. American Journal of Epidemiology 166, 1023–1034. [DOI] [PubMed] [Google Scholar]

[R31] Bonner MR, Lee WJ, Sandler DA, Hoppin JA, Dosemeci M, Alavanja MCR, 2005. Occupational exposure to carbofuran and the incidence of cancer in the Agricultural Health Study. Environ Health Persp 113, 285–289. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R32] Bonner MR, Williams BA, Rusiecki JA, Blair A, Freeman LEB, Hoppin JA, Dosemeci M, Lubin J, Sandler DP, Alavanja MCR, 2010. Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study. Cancer Cause Control 21, 871–877. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R33] Boyle T, Keegel T, Bull F, Heyworth J, Fritschi L, 2012. Physical Activity and Risks of Proximal and Distal Colon Cancers: A Systematic Review and Meta-analysis. Jnci-J Natl Cancer I 104, 1548–1561. [DOI] [PubMed] [Google Scholar]

[R34] Bradbury KE, Balkwill A, Spencer EA, Roddam AW, Reeves GK, Green J, Key TJ, Beral V, Pirie K, Collaborators MWS, 2014. Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom. Brit J Cancer 110, 2321–2326. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R35] Brownson RC, Reif JS, Chang JC, Davis JR, 1989. Cancer Risks among Missouri Farmers. Cancer-Am Cancer Soc 64, 2381–2386. [DOI] [PubMed] [Google Scholar]

[R36] Bueno de Demesquita HB, Doornbos G, Vanderkuip DAM, Kogevinas M, Winkelmann R, 1993. Occupational Exposure to Phenoxy Herbicides and Chlorophenols and Cancer Mortality in the Netherlands. Am J Ind Med 23, 289–300. [DOI] [PubMed] [Google Scholar]

[R37] Bunch TR, Gervais JA, Buhl K, Stone D, 2012. Dicamba General Fact Sheet National Pesticide Information Center, Oregon State University Extension Services. http://npic.orst.edu/factsheets/dicamba_gen.html. [Google Scholar]

[R38] Burmeister LF, 1981. Cancer Mortality in Iowa Farmers, 1971–78. Jnci-J Natl Cancer I 66, 461–464. [PubMed] [Google Scholar]

[R39] Burns C, Bodner K, Swaen G, Collins J, Beard K, Lee M, 2011. Cancer Incidence of 2,4-D Production Workers. Int J Env Res Pub He 8, 3579–3590. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R40] Burns CJ, 2005. Cancer among pesticide manufacturers and applicators. Scand J Work Env Hea 31, 9–17. [PubMed] [Google Scholar]

[R41] Burns CJ, Beard KK, Cartmill JB, 2001. Mortality in chemical workers potentially exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) 1945–94: an update. Occup Environ Med 58, 24–30. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R42] Callahan CL, Vena JE, Green J, Swanson M, Mu LN, Bonner MR, 2017. Consumption of Lake Ontario sport fish and the incidence of colorectal cancer in the New York State Angler Cohort Study (NYSACS). Environ Res 154, 86–92. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R43] Cantor KP, Silberman W, 1999. Mortality among aerial pesticide applicators and flight instructors: Follow-up from 1965–1988. Am J Ind Med 36, 239–247. [DOI] [PubMed] [Google Scholar]

[R44] Carter BD, Abnet CC, Feskanich D, Freedman ND, Hartge P, Lewis CE, Ockene JK, Prentice RL, Speizer FE, Thun MJ, Jacobs EJ, 2015. Smoking and Mortality - Beyond Established Causes. New Engl J Med 372, 631–640. [DOI] [PubMed] [Google Scholar]

[R45] CDC, 1993. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Heptachlor/Heptachlor Epoxide U.S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 1993. [Google Scholar]

[R46] Christensen CH, Platz EA, Andreotti G, Blair A, Hoppin JA, Koutros S, Lynch CF, Sandler DA, Alavanja MCR, 2010. Coumaphos Exposure and Incident Cancer among Male Participants in the Agricultural Health Study (AHS). Environ Health Persp 118, 92–96. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R47] Cocco P, Blair A, Congia P, Saba G, Flore C, Ecca MR, Palmas C, 1997. Proportional mortality of dichloro-diphenyl-trichloroethane (DDT) workers: A preliminary report. Arch Environ Health 52, 299–303. [DOI] [PubMed] [Google Scholar]

[R48] Coggon D, Pannett B, Winter PD, Acheson ED, Bonsall J, 1986. Mortality of Workers Exposed to 2 Methyl-4 Chlorophenoxyacetic Acid. Scand J Work Env Hea 12, 448–454. [DOI] [PubMed] [Google Scholar]

[R49] Cohen J, 1988. Statistical Power Analysis for the Behavioral-Sciences. Percept Motor Skill 67, 1007–1007. [Google Scholar]

[R50] Colt JS, Stallones L, Cameron LL, Dosemeci M, Zahm SH, 2001. Proportionate mortality among US migrant and seasonal farmworkers in twenty-four states. Am J Ind Med 40, 604–611. [DOI] [PubMed] [Google Scholar]

[R51] Cryder Z, Greenberg L, Richards J, Wolf D, Luo YZ, Gan J, 2019. Fiproles in urban surface runoff: Understanding sources and causes of contamination. Environ Pollut 250, 754–761. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R52] De Roos AJ, Blair A, Rusiecki JA, Hoppin JA, Svec M, Dosemeci M, Sandler DP, Alavanja MC, 2005. Cancer incidence among glyphosate-exposed pesticide applicators in the agricultural health study. Environ Health Persp 113, 49–54. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R53] Decoufle P, Stanislawczyk K, 1977. A retrospective survey of cancer in relation to occupation U.S. Dept. of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, Division of Surveillance, Hazard Evaluations for sale by the Supt. of Docs., U.S. Govt. Print. Off., Cincinnati, Washington. [Google Scholar]

[R54] Delancey JOL, Alavanja MCR, Coble J, Blair A, Hoppin JA, Austin HD, Freeman LEB, 2009. Occupational Exposure to Metribuzin and the Incidence of Cancer in the Agricultural Health Study. Annals of Epidemiology 19, 388–395. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R55] Delzell E, Grufferman S, 1985. Mortality among White and Nonwhite Farmers in North-Carolina, 1976–1978. American Journal of Epidemiology 121, 391–402. [DOI] [PubMed] [Google Scholar]

[R56] Demers PA, Davies HW, Friesen MC, Hertzman C, Ostry A, Hershler R, Teschke K, 2006. Cancer and occupational exposure to pentachlorophenol and tetrachlorophenol (Canada). Cancer Cause Control 17, 749–758. [DOI] [PubMed] [Google Scholar]

[R57] Depczynski J, Dobbins T, Armstrong B, Lower T, 2018a. Comparison of cancer incidence in Australian farm residents 45 years and over, compared to rural non-farm and urban residents - a data linkage study. Bmc Cancer 18. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R58] Depczynski J, Dobbins T, Armstrong B, Lower T, 2018b. Stage of diagnosis of prostate, breast and colorectal cancer in farm residents compared with other rural and urban residents in New South Wales. Aust J Rural Health 26, 56–62. [DOI] [PubMed] [Google Scholar]

[R59] Deziel NC, Freeman LEB, Hoppin JA, Thomas K, Lerro CC, Jones RR, Hines CJ, Blair A, Graubard BI, Lubin JH, Sandler DP, Chen HL, Andreotti G, Alavanja MC, Friesen MC, 2019. An algorithm for quantitatively estimating non-occupational pesticide exposure intensity for spouses in the Agricultural Health Study. J Expo Sci Env Epid 29, 344–357. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R60] Ditraglia D, Brown DP, Namekata T, Iverson N, 1981. Mortality Study of Workers Employed at Organochlorine Pesticide Manufacturing Plants. Scand J Work Env Hea 7, 140–146. [PubMed] [Google Scholar]

[R61] Dodge JL, Mills PK, Riordan DG, 2007. Cancer survival in California Hispanic farmworkers, 1988–2001. J Rural Health 23, 33–41. [DOI] [PubMed] [Google Scholar]

[R62] Dong K, 2007. Insect sodium channels and insecticide resistance. Invert Neurosci 7, 17–30. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R63] Donley N, 2019. The USA lags behind other agricultural nations in banning harmful pesticides. Environ Health-Glob 18. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R64] Dornetshuber-Fleiss R, Heffeter P, Mohr T, Hazemi P, Kryeziu K, Seger C, Berger W, Lemmens-Gruber R, 2013. Destruxins: Fungal-derived cyclohexadepsipeptides with multifaceted anticancer and antiangiogenic activities. Biochemical Pharmacology 86, 361–377. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R65] Dubrow R, Wegman DH, 1984. Occupational characteristics of cancer victims in Massachusetts 1971–1973 National Institute for Occupational Safety and Health, Cinncinnati, OH. (DHEW (NIOSH) publication no 84–109). [Google Scholar]

[R66] EPA, 1993. Butylate, R.E.D. Facts, Office of Prevention, Pesticides and Toxic Substances (7508W), EPA-738-F-93–014, U. S. Environmental Protection Agency, September 1993. . [Google Scholar]

[R67] EPA, 1994. Deposition of Air Pollutants to the Great Waters. First Report to Congress. EPA-453/R-93–055. Office of Air Quality Planning and Standards, Research Triangle Park, NC. U.S. Environmental Protection Agency, 1994. [Google Scholar]

[R68] EPA, 1996. Technical Factsheet on: TOXAPHENE. National Primary Drinking Water Regulations United States Environmental Protection Agency. [Google Scholar]

[R69] EPA, 1998. Reregistration Eligibility Decision (RED) for Alachlor; EPA 738-R-98–020, List A Case 0063, U.S [Google Scholar]

[R70] Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances (7508C), U.S. Government Printing Office: Washington, DC, 1998. [Google Scholar]

[R71] EPA, 1999. EPTC, R.E.D. Facts, Office of Prevention, Pesticides and Toxic Substances (7508W), EPA-738-F-99–011, U. S. Environmental Protection Agency, September 1999. . [Google Scholar]

[R72] EPA, 2002. Aldicarb (CASRN 116–06-3), Chemical Assessment Summary, Integrated Risk Information System (IRIS), National Center for Environmental Assessment, U. S. Environmental Protection Agency. . [Google Scholar]

[R73] EPA, 2004. Reregistration Eligibility Decision (RED) for MCPA (2-methyl-4-chlorophenoxyacetic acid); List A Case 0017, September 30, 2004, U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, U.S. Government Printing Office: Washington, DC, 2004. [Google Scholar]

[R74] EPA, 2005. Reregistration Eligibility Decision (RED) 2,4-D; EPA 738-R-05–002; U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, U.S. Government Printing Office: Washington, DC, 2005. [Google Scholar]

[R75] EPA, 2007. Pendimethalin. Human Health Risk Assessment for the Proposed Food Uses of the Herbicide, Memorandum, U. S. Environmental Protection Agency, Washington, DC, August 22, 2007. . [Google Scholar]

[R76] EPA, 2020. Basic Information about Pesticide Ingredients U.S. Environmental Protection Agency, January 21, 2020. [Google Scholar]

[R77] Faustini A, Forastiere F, Di Betta L, Magliola EM, Perucci CA, 1993. Cohort study of mortality among farmers and agricultural workers. Med Lav 84, 31–41. [PubMed] [Google Scholar]

[R78] FDA, 2018. Pesticide Reidue Monitoring Program Fiscal Year 2018 Pesticide Report, U.S. Food and Drug Administration, 2018. . [Google Scholar]

[R79] Figa-Talamanca I, Mearelli I, Valente P, Bascherini S, 1993. Cancer Mortality in a Cohort of Rural Licensed Pesticide Users in the Province of Rome. Int J Epidemiol 22, 579–583. [DOI] [PubMed] [Google Scholar]

[R80] Fincham SM, Hanson J, Berkel J, 1992. Patterns and Risks of Cancer in Farmers in Alberta. Cancer-Am Cancer Soc 69, 1276–1285. [DOI] [PubMed] [Google Scholar]

[R81] Fleming LE, Bean JA, Rudolph M, Hamilton K, 1999a. Cancer incidence in a cohort of licensed pesticide applicators in Florida. J Occup Environ Med 41, 279–288. [DOI] [PubMed] [Google Scholar]

[R82] Fleming LE, Bean JA, Rudolph M, Hamilton K, 1999b. Mortality in a cohort of licenced pesticide applicators in Florida. Occup Environ Med 56, 14–21. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R83] Forastiere F, Quercia A, Miceli M, Settimi L, Terenzoni B, Rapiti E, Faustini A, Borgia P, Cavariani F, Perucci CA, 1993. Cancer among Farmers in Central Italy. Scand J Work Env Hea 19, 382–389. [DOI] [PubMed] [Google Scholar]

[R84] Fox AJ, Goldblatt PO, 1980. Longitudinal study of sociodemographic mortality differentials, 1971–1975, Office of Population Census and Surveys. Her Majesty’s Stationary Office, London. (Series LS no 1). [Google Scholar]

[R85] Fragar L, Depczynski J, Lower T, 2011. Mortality patterns of Australian male farmers and farm managers. Aust J Rural Health 19, 179–184. [DOI] [PubMed] [Google Scholar]

[R86] Franceschi S, Barbone F, Bidoli E, Guarneri S, Serraino D, Talamini R, La Vecchia C, 1993. Cancer risk in farmers: results from a multi-site case-control study in north-eastern Italy. Int J Cancer 53, 740–745. [DOI] [PubMed] [Google Scholar]

[R87] Fukuto TR, 1990. Mechanism of Action of Organophosphorus and Carbamate Insecticides. Environ Health Persp 87, 245–254. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R88] Gallagher RP, Threlfall WJ, Band PR, 1989. Occupational Mortality diseases in occupations with potential exposure to phenoxyacetic acids in British Columbia 1950–84 Cancer Control Agency of British Columbia. [Google Scholar]

[R89] Gallagher RP, Threlfall WJ, Jeffries E, Band PR, Spinelli J, Coldman AJ, 1984. Cancer and Aplastic-Anemia in British-Columbia Farmers. J Natl Cancer I 72, 1311–1315. [PubMed] [Google Scholar]

[R90] Garabrant DH, Peters JM, Mack TM, Bernstein L, 1984. Job Activity and Colon Cancer Risk. American Journal of Epidemiology 119, 1005–1014. [DOI] [PubMed] [Google Scholar]

[R91] Greenburg DL, Rusiecki J, Koutros S, Dosemeci M, Patel R, Hines CJ, Hoppin JA, Alavanja MCR, 2008. Cancer incidence among pesticide applicators exposed to captan in the Agricultural Health Study. Cancer Cause Control 19, 1401–1407. [DOI] [PubMed] [Google Scholar]

[R92] Grossmann K, 2010. Auxin herbicides: current status of mechanism and mode of action. Pest Manag Sci 66, 113–120. [DOI] [PubMed] [Google Scholar]

[R93] Gunnarsdottir H, Rafnsson V, 1991. Cancer Incidence among Icelandic Farmers 1977–1987. Scand J Soc Med 19, 170–173. [DOI] [PubMed] [Google Scholar]

[R94] Guralnick L, 1963. Mortality by occupation and cause of death Department of Health, Education, and Welfare, Washington, DC; 1963. (Vital statistics speecial report 53(3), DHEW (PHS)). [Google Scholar]

[R95] Hall RCW, Hall RCW, 1999. Long-term psychological and neurological complications of lindane poisoning. Psychosomatics 40, 513–517. [DOI] [PubMed] [Google Scholar]

[R96] Harrahy E, 2003a. Multi-use Fact Sheet for Acetochlor: (Aquatic Life - acute concentration), Wisconsin Department of Natural Resources, 2003. [Google Scholar]

[R97] Harrahy E, 2003b. Multi-use Fact Sheet for Triflurlin: (Aquatic Life - acute concentration), Wisconsin Department of Natural Resources, 2003. [Google Scholar]

[R98] Helweg A, 1987. Degradation and Adsorption of C-14 Mcpa in Soil - Influence of Concentration, Temperature and Moisture-Content on Degradation. Weed Res 27, 287–296. [Google Scholar]

[R99] Hoar SK, Blair A, Holmes FF, Boysen C, Robel RJ, 1985. Herbicides and Colon Cancer. Lancet 1, 1277–1278. [DOI] [PubMed] [Google Scholar]

[R100] Holten R, Boe FN, Almvik M, Katuwal S, Stenrod M, Larsbo M, Jarvis N, Eklo OM, 2018. The effect of freezing and thawing on water flow and MCPA leaching in partially frozen soil. J Contam Hydrol 219, 72–85. [DOI] [PubMed] [Google Scholar]

[R101] Hou LF, Lee WJ, Rusiecki J, Hoppin JA, Blair A, Bonner MR, Lubin JH, Samanic C, Sandler DP, Dosemeci M, Alavanja MCR, 2006. Pendimethalin exposure and cancer incidence among pesticide applicators. Epidemiology 17, 302–307. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R102] Howe GR, Lindsay JP, 1983. A follow-up study of a ten-percent sample of the Canadian labor force. I. Cancer mortality in males, 1965–73. J Natl Cancer Inst 70, 37–44. [PubMed] [Google Scholar]

[R103] Howsam M, Grimalt JO, Guino E, Navarro M, Marti-Rague J, Peinado MA, Capella G, Moreno V, Grp BCC, 2004. Organochlorine exposure and colorectal cancer risk. Environ Health Persp 112, 1460–1466. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R104] HSDB, 1993. U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database) National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993. [Google Scholar]

[R105] Ilgaz A, Gozum S, 2018. Determination of Colorectal Cancer Risk Levels, Colorectal Cancer Screening Rates, and Factors Affecting Screening Participation of Individuals Working in Agriculture in Turkey. Cancer Nurs 41, E46–E54. [DOI] [PubMed] [Google Scholar]

[R106] Kachuri L, Harris MA, MacLeod JS, Tjepkema M, Peters PA, Demers PA, 2017. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC). Bmc Cancer 17. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R107] Kaerlev L, Lynge E, Sabroe S, Olsen J, 2004. Colon cancer controls versus population controls in case-control studies of occupational risk factors. Bmc Cancer 4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R108] Kang D, Park SK, Beane-Freeman L, Lynch CF, Knott CE, Sandler DP, Hoppin JA, Dosemeci M, Coble J, Lubin J, Blair A, Alavanja M, 2008. Cancer incidence among pesticide applicators exposed to trifluralin in the Agricultural Health Study. Environ Res 107, 271–276. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R109] Keller JE, Howe HL, 1994. Case-Control Studies of Cancer in Illinois Farmers Using Data from the Illinois-State-Cancer-Registry and the Us-Census-of-Agriculture. European Journal of Cancer 30a, 469–473. [DOI] [PubMed] [Google Scholar]

[R110] Kogevinas M, Becher H, Benn T, Bertazzi PA, Boffetta P, BuenodeMesquita HB, Coggon D, Colin D, FleschJanys D, Fingerhut M, Green L, Kauppinen T, Littorin M, Lynge E, Mathews JD, Neuberger M, Pearce N, Saracci R, 1997. Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins - An expanded and updated international cohort study. American Journal of Epidemiology 145, 1061–1075. [DOI] [PubMed] [Google Scholar]

[R111] Koutros S, Lynch CF, Ma XM, Lee WJ, Hoppin JA, Christensen CH, Andreotti G, Freeman LB, Rusiecki JA, Hou LF, Sandler DP, Alavanja MCR, 2009. Heterocyclic aromatic amine pesticide use and human cancer risk: Results from the US Agricultural Health Study. International Journal of Cancer 124, 1206–1212. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R112] Koutros S, Mahajan R, Zheng TZ, Hoppin JA, Ma XM, Lynch CF, Blair A, Alavanja MCR, 2008. Dichlorvos exposure and human cancer risk: results from the Agricultural Health Study. Cancer Cause Control 19, 59–65. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R113] Lee WJ, Alavania MCR, Hoppin JA, Rusiecki JA, Kamel F, Blair A, Sandler DP, 2007a. Mortality among pesticide applicators exposed to chlorpyrifos in the agricultural health study. Environ Health Persp 115, 528–534. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R114] Lee WJ, Blair A, Hoppin JA, Lubin JH, Rusiecki JA, Sandler DP, Dosemeci M, Alavanja MCR, 2004a. Cancer incidence among pesticide applicators exposed to chlorpyrifos in the agricultural health study. Jnci-J Natl Cancer I 96, 1781–1789. [DOI] [PubMed] [Google Scholar]

[R115] Lee WJ, Hoppin JA, Blair A, Lubin JH, Dosemeci M, Sandler DP, Alavanja MCR, 2004b. Cancer incidence among pesticide applicators exposed to alachlor in the Agricultural Health Study. American Journal of Epidemiology 159, 373–380. [DOI] [PubMed] [Google Scholar]

[R116] Lee WJ, Sandler DP, Blair A, Samanic C, Cross AJ, Alavanja MCR, 2007b. Pesticide use and colorectal cancer risk in the Agricultural Health Study. International Journal of Cancer 121, 339–346. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R117] Lee WJ, Son M, Chun BC, Park ES, Lee HK, Coble J, Dosemeci M, 2008. Cancer mortality and farming in South Korea: an ecologic study. Cancer Cause Control 19, 505–513. [DOI] [PubMed] [Google Scholar]

[R118] Lee YM, Kim SA, Choi GS, Park SY, Jeon SW, Lee HS, Lee SJ, Heo S, Lee DH, 2018. Association of colorectal polyps and cancer with low-dose persistent organic pollutants: A case-control study. Plos One 13. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R119] Leet T, Acquavella J, Lynch C, Anne M, Weiss NS, Vaughan T, Checkoway H, 1996. Cancer incidence among alachlor manufacturing workers. Am J Ind Med 30, 300–306. [DOI] [PubMed] [Google Scholar]

[R120] Lerro CC, Koutros S, Andreotti G, Friesen MC, Alavanja MC, Blair A, Hoppin JA, Sandler DP, Lubin JH, Ma XM, Zhang YW, Freeman LEB, 2015a. Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study. Occup Environ Med 72, 736–744. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R121] Lerro CC, Koutros S, Andreotti G, Hines CJ, Blair A, Lubin J, Ma XM, Zhang YW, Beane Freeman LE, 2015b. Use of acetochlor and cancer incidence in the Agricultural Health Study. International Journal of Cancer 137, 1167–1175. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R122] Limay-Rios V, Forero LG, Xue YG, Smith J, Baute T, Schaafsma A, 2016. Neonicotinoid insecticide residues in soil dust and associated parent soil in fields with a history of seed treatment use on crops in southwestern Ontario. Environ Toxicol Chem 35, 303–310. [DOI] [PubMed] [Google Scholar]

[R123] Littorin M, Attewell R, Skerfving S, Horstmann V, Moller T, 1993. Mortality and Tumor Morbidity among Swedish Market Gardeners and Orchardists. Int Arch Occ Env Hea 65, 163–169. [DOI] [PubMed] [Google Scholar]

[R124] Lo AC, Soliman AS, Khaled HM, Aboelyazid A, Greenson JK, 2010. Lifestyle, Occupational, and Reproductive Factors and Risk of Colorectal Cancer. Diseases of the Colon & Rectum 53, 830–837. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R125] Louis LM, Lerro CC, Friesen MC, Andreotti G, Koutros S, Sandler DP, Blair A, Robson MG, Freeman LEB, 2017. A prospective study of cancer risk among Agricultural Health Study farm spouses associated with personal use of organochlorine insecticides. Environ Health-Glob 16. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R126] Lynch SM, Mahajan R, Freeman LEB, Hoppin JA, Alavanja MCR, 2009. Cancer incidence among pesticide applicators exposed to butylate in the Agricultural Health Study (AHS). Environ Res 109, 860–868. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R127] Lynch SM, Rusiecki JA, Blair A, Dosemeci M, Lubin J, Sandler D, Hoppin JA, Lynch CF, Alavanja MCR, 2006. Cancer incidence among pesticide applicators exposed to cyanazine in the agricultural health study. Environ Health Persp 114, 1248–1252. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R128] Lynge E, 1998. Cancer incidence in Danish phenoxy herbicide workers, 1947–1993. Environ Health Persp 106, 683–688. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R129] Ma Y, Yang W, Song M, Smith-Warner SA, Yang J, Li Y, Ma W, Hu Y, Ogino S, Hu FB, Wen D, Chan AT, Giovannucci EL, Zhang X, 2018. Type 2 diabetes and risk of colorectal cancer in two large U.S. prospective cohorts. Br J Cancer 119, 1436–1442. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R130] MacLennan PA, Delzell E, Sathiakumar N, Myers SL, Cheng H, Grizzle W, Chen VW, Wu XC, 2002. Cancer incidence among triazine herbicide manufacturing workers. J Occup Environ Med 44, 1048–1058. [DOI] [PubMed] [Google Scholar]

[R131] MacMahon B, Monson RR, Wang HH, Zheng TZ, 1988. A second follow-up of mortality in a cohort of pesticide applicators. J Occup Med 30, 429–432. [DOI] [PubMed] [Google Scholar]

[R132] Mahajan R, Blair A, Coble J, Lynch CF, Hoppin JA, Sandler DP, Alavanja MCR, 2007. Carbaryl exposure and incident cancer in the Agricultural Health Study. International Journal of Cancer 121, 1799–1805. [DOI] [PubMed] [Google Scholar]

[R133] Mahajan R, Blair A, Lynch CF, Schroeder P, Hoppin JA, Sandler DP, Alavanja MCR, 2006a. Fonofos exposure and cancer incidence in the Agricultural Health Study. Environ Health Persp 114, 1838–1842. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R134] Mahajan R, Bonner MR, Hoppin JA, Alavanja MCR, 2006b. Phorate exposure and incidence of cancer in the agricultural health study. Environ Health Persp 114, 1205–1209. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R135] Martin FL, Martinez EZ, Stopper H, Garcia SB, Uyemura SA, Kannen V, 2018. Increased exposure to pesticides and colon cancer: Early evidence in Brazil. Chemosphere 209, 623–631. [DOI] [PubMed] [Google Scholar]

[R136] McMichael AJ, Hartshorne JM, 1982. Mortality Risks in Australian Men by Occupational Groups, 1968–1978 Variations Associated with Differences in Drinking and Smoking-Habits. Med J Australia 1, 253–256. [PubMed] [Google Scholar]

[R137] McNabb S, Harrison TA, Albanes D, Berndt SI, Brenner H, Caan BJ, Campbell PT, Cao Y, Chang-Claude J, Chan A, Chen Z, English DR, Giles GG, Giovannucci EL, Goodman PJ, Hayes RB, Hoffmeister M, Jacobs EJ, Joshi AD, Larsson SC, Le Marchand L, Li L, Lin Y, Mannisto S, Milne RL, Nan H, Newton CC, Ogino S, Parfrey PS, Petersen PS, Potter JD, Schoen RE, Slattery ML, Su YR, Tangen CM, Tucker TC, Weinstein SJ, White E, Wolk A, Woods MO, Phipps AI, Peters U, 2020. Meta-analysis of 16 studies of the association of alcohol with colorectal cancer. Int J Cancer 146, 861–873. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R138] Milham SJ, 1983. Occupational mortality in Washington State, 1950–1979 National Institute for Occupational Safety and Health, Cinncinnati, OH. (DHHS publication no (NIOSH) 83–116). [Google Scholar]

[R139] Mills PK, Kwong S, 2001. Cancer incidence in the united farmworkers of America (UFW), 1987–1997. Am J Ind Med 40, 596–603. [DOI] [PubMed] [Google Scholar]

[R140] Moher D, Liberati A, Tetzlaff J, Altman DG, Grp P, 2009. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Plos Medicine 6. [PMC free article] [PubMed] [Google Scholar]

[R141] Mozzachio AM, Rusiecki JA, Hoppin JA, Mahajan R, Patel R, Beane-Freeman L, Alavanja MCR, 2008. Chlorothalonil exposure and cancer incidence among pesticide applicator participants in the agricultural health study. Environ Res 108, 400–403. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R142] Murillo G, Kosmeder JW, Pezzuro JM, Mehta RG, 2003. Deguelin suppresses the formation of carcinogen-induced aberrant crypt foci in the colon of CF-1 mice. International Journal of Cancer 104, 7–11. [DOI] [PubMed] [Google Scholar]

[R143] Murillo G, Salti GI, Kosmeder JW, Pezzuto JM, Mehta RG, 2002. Deguelin inhibits the growth of colon cancer cells through the induction of apoptosis and cell cycle arrest. European Journal of Cancer 38, 2446–2454. [DOI] [PubMed] [Google Scholar]

[R144] Narahashi T, 2002. Nerve Membrane Ion Channels as the Target Site of Insecticides. Mini-Rev Med Chem 2, 419–432. [DOI] [PubMed] [Google Scholar]

[R145] Nasterlack M, Hoffmann G, Messerer P, Ott MG, Pallapies D, Wrede M, Zober A, 2007. Epidemiological and clinical investigations among employees in a former herbicide production process. Int Arch Occ Env Hea 80, 234–238. [DOI] [PubMed] [Google Scholar]

[R146] NPIC, 2008. 2,4-D Technical Fact Sheet, National Pesticide Information Center, Oregon State University and U. S. Environmental Protection Agency, 2008. [Google Scholar]

[R147] Oddone E, Modonesi C, Gatta G, 2014. Occupational exposures and colorectal cancers: A quantitative overview of epidemiological evidence. World J Gastroentero 20, 12431–12444. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R148] Olsen JH, Jensen OM, 1987. Occupation and Risk of Cancer in Denmark - an Analysis of 93810 Cancer Cases, 1970–1979 - Preface. Scand J Work Env Hea 13, 1-+. [PubMed] [Google Scholar]

[R149] PAN, 2020. Consolidated List of Banned Pesticides, Pesticide Action Network. [Google Scholar]

[R150] Park SK, Kang D, Beane-Freeman L, Blair A, Hoppin JA, Sandler DP, Lynch CF, Knott C, Gwak J, Alavanja M, 2009. Cancer Incidence Among Paraquat Exposed Applicators in the Agricultural Health Study Prospective Cohort Study. Int J Occup Env Heal 15, 274–281. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R151] Parron T, Requena M, Hernandez AF, Alarcon R, 2014. Environmental exposure to pesticides and cancer risk in multiple human organ systems. Toxicol Lett 230, 157–165. [DOI] [PubMed] [Google Scholar]

[R152] Peterson GR, Milham SJ, 1980. Occupational mortality in the state of California, 1959–1961 National Institute for Occupational Safety and Health, Rockville, MD. (DHEW publication no (NIOSH, NIH) 80–104). [Google Scholar]

[R153] Powis G, Gallegos A, Abraham RT, Ashendel CL, Zalkow LH, Dorr R, Dvorakova K, Salmon S, Harrison S, Worzalla J, 1997. Inhibition of intracellular Ca2+ signalling, cytotoxicity and antitumor activity of the herbicide oryzalin and its analogues. Cancer Chemoth Pharm 41, 22–28. [DOI] [PubMed] [Google Scholar]

[R154] Purdue MP, Hoppin JA, Blair A, Dosemeci M, Alavanja MCR, 2007. Occupational exposure to organochlorine insecticides and cancer incidence in the Agricultural Health Study. International Journal of Cancer 120, 642–649. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R155] Rafnsson V, 2006. Cancer incidence among farmers exposed to lindane while sheep dipping. Scand J Work Env Hea 32, 185–189. [DOI] [PubMed] [Google Scholar]

[R156] Rafnsson V, Gunnarsdottir H, 1989. Mortality among Farmers in Iceland. Int J Epidemiol 18, 146–151. [DOI] [PubMed] [Google Scholar]

[R157] Reif J, Pearce N, Fraser J, 1989. Cancer Risks in New-Zealand Farmers. Int J Epidemiol 18, 768–774. [DOI] [PubMed] [Google Scholar]

[R158] Ronco G, Costa G, Lynge E, 1992. Cancer Risk among Danish and Italian Farmers. Brit J Ind Med 49, 220–225. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R159] Rusiecki JA, De Roos A, Lee WJ, Dosemeci M, Lubin JH, Hoppin JA, Blair A, Alavanja MCR, 2004. Cancer incidence among pesticide applicators exposed to atrazine in the agricultural health study. Jnci-J Natl Cancer I 96, 1375–1382. [DOI] [PubMed] [Google Scholar]

[R160] Rusiecki JA, Hou LF, Lee WJ, Blair A, Dosemeci M, Lubin JH, Bonner M, Samanic C, Hoppin JA, Sandler DP, Alavanja MCR, 2006. Cancer incidence among pesticide applicators exposed to metolachlor in the Agricultural Health Study. International Journal of Cancer 118, 3118–3123. [DOI] [PubMed] [Google Scholar]

[R161] Rusiecki JA, Patel R, Koutros S, Beane-Freeman L, Landgren O, Bonner MR, Coble J, Lubin J, Blair A, Hoppin JA, Alavanja MCR, 2009. Cancer Incidence among Pesticide Applicators Exposed to Permethrin in the Agricultural Health Study. Environ Health Persp 117, 581–586. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R162] Saftlas AF, Blair A, Cantor KP, Hanrahan L, Anderson HA, 1987. Cancer and Other Causes of Death among Wisconsin Farmers. Am J Ind Med 11, 119–129. [DOI] [PubMed] [Google Scholar]

[R163] Salerno C, Carcagni A, Sacco S, Palin LA, Vanhaecht K, Panella M, Guido D, 2016. An Italian population-based case-control study on the association between farming and cancer: Are pesticides a plausible risk factor? Arch Environ Occup H 71, 147–156. [DOI] [PubMed] [Google Scholar]

[R164] Samanic C, Rusiecki J, Dosemeci M, Hou L, Hoppin JA, Sandler DP, Lubin J, Blair A, Alavanja MCR, 2006. Cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study. Environ Health Persp 114, 1521–1526. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R165] Sathiakumar N, Delzell E, Cole P, 1996. Mortality among workers at two triazine herbicide manufacturing plants. Am J Ind Med 29, 143–151. [DOI] [PubMed] [Google Scholar]

[R166] Schreinemachers DM, 2000. Cancer mortality in four northern wheat-producing states. Environ Health Persp 108, 873–881. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R167] Schwartz E, Grady K, 1986. Patterns of occupationalmortality in New Hampshire 1975–1985 Concord, NH: New Hampshire Division of Public Health Services. [Google Scholar]

[R168] Senseman SA, 2007. Herbicide Handbook, Ninth Edition Weed Sci. Soc. Am. Champaign, IL: 458 pp. 2007. [Google Scholar]

[R169] Settimi L, Comba P, Bosia S, Ciapini C, Desideri E, Fedi A, Perazzo PL, Axelson O, 2001. Cancer risk among male farmers: a multi-site case-control study. Int J Occup Med Environ Health 14, 339–347. [PubMed] [Google Scholar]

[R170] Sjerps RMA, Kooij PJF, van Loon A, Van Wezel AP, 2019. Occurrence of pesticides in Dutch drinking water sources. Chemosphere 235, 510–518. [DOI] [PubMed] [Google Scholar]

[R171] Soliman AS, Smith MA, Cooper SP, Ismail K, Khaled H, Ismail S, McPherson RS, Seifeldin IA, Bondy ML, 1997. Serum organochlorine pesticide levels in patients with colorectal cancer in Egypt. Arch Environ Health 52, 409–415. [DOI] [PubMed] [Google Scholar]

[R172] Stark AD, Chang HG, Fitzgerald EF, Riccardi K, Stone RR, 1987. A Retrospective Cohort Study of Mortality among New-York-State Farm Bureau Members. Arch Environ Health 42, 204–212. [PubMed] [Google Scholar]

[R173] Su F-C, Goutman SA, Chernyak S, Mukherjee B, Callaghan BC, Batterman S, Feldman EL, 2016. The Role of Environmental Toxins on ALS: A Case-Control Study of Occupational Risk Factors. JAMA Neurol 73, 803–811. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R174] Sultana T, Murray C, Kleywegt S, Metcalfe CD, 2018. Neonicotinoid pesticides in drinking water in agricultural regions of southern Ontario, Canada. Chemosphere 202, 506–513. [DOI] [PubMed] [Google Scholar]

[R175] Sunol C, Tusell JM, Gelpi E, Rodriguezfarre E, 1989. Gabaergic Modulation of Lindane (Gamma-Hexachlorocyclohexane)-Induced Seizures. Toxicol Appl Pharm 100, 1–8. [DOI] [PubMed] [Google Scholar]

[R176] Swaen GMH, de Jong G, Slangen JJM, van Amelsvoort LG, 2002. Cancer mortality in workers exposed to dieldrin and aldrin: an update. Toxicol Ind Health 18, 63–70. [DOI] [PubMed] [Google Scholar]

[R177] Swaen GMH, van Amelsvoort LGPM, Slangen JJM, Mohren DCL, 2004. Cancer mortality in a cohort of licensed herbicide applicators. Int Arch Occ Env Hea 77, 293–295. [DOI] [PubMed] [Google Scholar]

[R178] Swaen GMH, Vanvliet C, Slangen JJM, Sturmans F, 1992. Cancer Mortality among Licensed Herbicide Applicators. Scand J Work Env Hea 18, 201–204. [DOI] [PubMed] [Google Scholar]

[R179] Sweden S, 1981. Dodsfalls registret 1961–1970 Stockholm. [Google Scholar]

[R180] Tan Z, Zhou J, Chen H, Zou Q, Weng S, Luo T, Tang Y, 2016. Toxic effects of 2,4-dichlorophenoxyacetic acid on human sperm function in vitro. J Toxicol Sci 41, 543–549. [DOI] [PubMed] [Google Scholar]

[R181] Torchio P, Lepore AR, Corrao G, Comba P, Settimi L, Belli S, Magnani C, Diorio F, 1994. Mortality Study on a Cohort of Italian Licensed Pesticide Users. Science of the Total Environment 149, 183–191. [DOI] [PubMed] [Google Scholar]

[R182] Une H, Schuman SH, Caldwell ST, Whitlock NH, 1987. Agricultural Life-Style - a Mortality Study among Male Farmers in South-Carolina, 1983–1984. South Med J 80, 1137–1140. [PubMed] [Google Scholar]

[R183] USGS, 2017. Pesticide National Synthesis Project, Estimated Annual Agricultural Pesticide Use, Archived preliminary county level pesticide use estimates, United States Geological Survey. [Google Scholar]

[R184] Uysal M, Bozcuk H, Karakilinc H, Goksu S, Tatli AM, Gunduz S, Arslan D, Coskun HS, Savas B, 2013. Pesticides and Cancer: The First Incidence Study Conducted in Turkey. J Environ Pathol Tox 32, 245–249. [DOI] [PubMed] [Google Scholar]

[R185] van Amelsvoort LGPM, Slangen JJM, Tsai SP, de Jong G, Kant I, 2009. Cancer mortality in workers exposed to dieldrin and aldrin: over 50 years of follow up. Int Arch Occ Env Hea 82, 217–225. [DOI] [PubMed] [Google Scholar]

[R186] van Bemmel DM, Visvanathan K, Freeman LEB, Coble J, Hoppin JA, Alavanja MCR, 2008. S-Ethyl-N,N-dipropylthiocarbamate Exposure and Cancer Incidence among Male Pesticide Applicators in the Agricultural Health Study: A Prospective Cohort. Environ Health Persp 116, 1541–1546. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R187] Versluys JJ, 1949. Cancer and Occupation in the Netherlands. Brit J Cancer 3, 161–185. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R188] Vieira AR, Abar L, Chan DSM, Vingeliene S, Polemiti E, Stevens C, Greenwood D, Norat T, 2017. Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project. Annals of Oncology 28, 1788–1802. [DOI] [PubMed] [Google Scholar]

[R189] Wales CTK, Taylor FR, Higa AT, McAllister HA, Jacobs AT, 2015. ERK-dependent phosphorylation of HSF1 mediates chemotherapeutic resistance to benzimidazole carbamates in colorectal cancer cells. Anti-Cancer Drug 26, 657–666. [DOI] [PubMed] [Google Scholar]

[R190] Walrath JJ, Rogot E, Murray J, Blair A, 1985. Mortality patterns among US veterans by occupation and smoking status US Government Printing Office, Washington, DC. (NIH publication no 85–2756). [Google Scholar]

[R191] Wang HH, Macmahon B, 1979. Mortality of Workers Employed in the Manufacture of Chlordane and Heptachlor. J Occup Environ Med 21, 745–748. [DOI] [PubMed] [Google Scholar]

[R192] Wang Y, Hwang SA, Lewis-Michl EL, Fitzgerald EF, Stark AD, 2003. Mortality among a cohort of female farm residents in New York State. Arch Environ Health 58, 642–648. [DOI] [PubMed] [Google Scholar]

[R193] Wang Y, Lewis-Michl EL, Hwang SA, Fitzgerald EF, Stark AD, 2002. Cancer incidence among a cohort of female farm residents in New York State. Arch Environ Health 57, 561–567. [DOI] [PubMed] [Google Scholar]

[R194] Weichenthal S, Moase C, Chan P, 2010. A Review of Pesticide Exposure and Cancer Incidence in the Agricultural Health Study Cohort. Environ Health Persp 118, 1117–1125. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R195] Weichenthal S, Moase C, Chan P, 2012. A Review of Pesticide Exposure and Cancer Incidence in the Agricultural Health Study Cohort. Cienc Saude Coletiva 17, 255–270. [DOI] [PubMed] [Google Scholar]

[R196] Wesseling C, Antich D, Hogstedt C, Rodriguez AC, Ahlbom A, 1999. Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure. Int J Epidemiol 28, 365–374. [DOI] [PubMed] [Google Scholar]

[R197] WHO, 2019. Recommended Classification of Pesticides by Hazard and Guidelines to Classification, World Health Organization. [Google Scholar]

[R198] WHO, 2020. International Agency for Research on Cancer Monographs on the Identification of Carcinogenic Hazards to Humans, World Health Organization, 2020. [Google Scholar]

[R199] Wiklund K, 1986. Cancer risks among agricultural workers in Sweden. Cohort studies based on Swedish cancer-environment register Karolinska hospital, Stockholm. [Google Scholar]

[R200] Wiklund K, Dich J, 1994. Cancer Risks among Female Farmers in Sweden. Cancer Cause Control 5, 449–457. [DOI] [PubMed] [Google Scholar]

[R201] Wiklund K, Dich J, Holm LE, Eklund G, 1989. Risk of Cancer in Pesticide Applicators in Swedish Agriculture. Brit J Ind Med 46, 809–814. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R202] Wiklund K, Einhorn J, Wennstrom G, 1981. A Swedish Cancer-Environment Register Available for Research. Scand J Work Env Hea 7, 64–67. [DOI] [PubMed] [Google Scholar]

[R203] Wilkinson P, Thakrar B, Shaddick G, Stevenson S, Pattenden S, Landon M, Grundy C, Elliott P, 1997. Cancer incidence and mortality around the Pan Britannica Industries pesticide factory, Waltham Abbey. Occup Environ Med 54, 101–107. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R204] Williams RR, Stegens NL, Goldsmith JR, 1977. Associations of cancer site and type with occupation and industry from the Third National Cancer Survey Interview. J Natl Cancer Inst 59, 1147–1185. [DOI] [PubMed] [Google Scholar]

[R205] Wong O, Brocker W, Davis HV, Nagle GS, 1984. Mortality of Workers Potentially Exposed to Organic and Inorganic Brominated Chemicals, Dbcp, Tris, Pbb, and Ddt. Brit J Ind Med 41, 15–24. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R206] Xu C, Chen L, You LH, Xu Z, Ren LF, Gin KYH, He YL, Kai WZ, 2018. Occurrence, impact variables and potential risk of PPCPs and pesticides in a drinking water reservoir and related drinking water treatment plants in the Yangtze Estuary. Environ Sci-Proc Imp 20, 1030–1045. [DOI] [PubMed] [Google Scholar]

[R207] Xue K, Li FF, Chen YW, Zhou YH, He J, 2017. Body mass index and the risk of cancer in women compared with men: a meta-analysis of prospective cohort studies. European Journal of Cancer Prevention 26, 94–105. [DOI] [PubMed] [Google Scholar]

[R208] Yi SW, 2013. Cancer incidence in Korean Vietnam veterans during 1992–2003: the Korean veterans health study. J Prev Med Public Health 46, 309–318. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R209] Yi SW, Ohrr H, Hong JS, Yi JJ, 2013. Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans. J Prev Med Public Health 46, 213–225. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R210] Yi SW, Ryu SY, Ohrr H, Hong JS, 2014. Agent Orange exposure and risk of death in Korean Vietnam veterans: Korean Veterans Health Study. Int J Epidemiol 43, 1825–1834. [DOI] [PubMed] [Google Scholar]

[R211] Yoshitani SI, Tanaka T, Kohno H, Takashima S, 2001. Chemoprevention of azoxymethane-induced rat colon carcinogenesis by dietary capsaicin and rotenone. Int J Oncol 19, 929–939. [DOI] [PubMed] [Google Scholar]

[R212] Zahm SH, 1997. Mortality study of pesticide applicators and other employees of a lawn care service company. J Occup Environ Med 39, 1055–1067. [DOI] [PubMed] [Google Scholar]

[R213] Zhong Y, Rafnsson V, 1996. Cancer incidence among Icelandic pesticide users. Int J Epidemiol 25, 1117–1124. [DOI] [PubMed] [Google Scholar]

[R214] Zhou Y, Liu JQ, Zhou ZH, Lv XT, Chen YQ, Sun LQ, Chen FX, 2016. Enhancement of CD3AK cell proliferation and killing ability by alpha-Thujone. Int Immunopharmacol 30, 57–61. [DOI] [PubMed] [Google Scholar]

PERMALINK

Association between Pesticide Exposure and Colorectal Cancer Risk and Incidence: A Systematic Review

Eryn K Matich

Jonathan A Laryea

Kathryn A Seely

Shelbie Stahr

L Joseph Su

Ping-Ching Hsu

Abstract

Background

Objectives

Methods

Results

Discussion

1. Introduction

Table 1.

2. Methods

2.1. Literature Search

Figure 1.

2.2. Eligibility Criteria

2.3. Data Collection Process

3. Results and Discussion

3.1. Study Selection, Population, and Characteristics

Table 2.

Table 6.

3.2. Studies Analyzing Certain Pesticides Exposure and Colon Cancer, Rectal Cancer, and CRC Risk

Figure 2. Forest Plot of the Associations (effect size: RR, HR, OR, SIR, or PMR and 95% CI) Between Certain Pesticide Exposure and Colon Cancer Risk.

Figure 4. Forest Plot of the Associations (effect size: RR, OR, or SIR and 95% CI) Between Certain Pesticide Exposure and CRC Risk.

Table 5.

Table 3.

Figure 3. Forest Plot of the Associations (effect sizes: RR, OR, SMR, SRR, and SIR and 95% CI) Between Certain Pesticide Exposure and Rectal Cancer Risk.

Table 4.

3.2.1. Organochlorine Insecticides

3.2.2. Organophosphate Insecticides

3.2.3. Carbamate Insecticides

3.2.4. Chlorophenoxy Herbicides

3.2.5. Anilide/ Aniline Herbicides

3.2.6. Other Pesticides

3.2.7. Discussion of Pesticide Exposure and Colon Cancer Risk

3.2.8. Discussion of Pesticide Exposure and Rectal Cancer Risk

3.2.9. Discussion of Pesticide Exposure and CRC Risk

3.2.10. Summary of Pesticide Exposure and Colon Cancer, Rectal Cancer, and CRC Risk

3.3. Studies Analyzing the Association between General Pesticide Exposure and Colon Cancer, Rectal Cancer, and CRC Risk

Figure 5. Forest Plot of the Associations (effect size: RR, OR, HR, SMR, PMR, SIR, PCMR and 95% CI) Between Pesticide Exposure from Farming or Agricultural Work and Colon Cancer, Rectal Cancer, or CRC Risk.

Figure 7. Forest Plot of the Associations (effect size: OR, RR, SIR, and 95% CI) Between Environmental Pesticide Exposure and Colon Cancer, Rectal Cancer, or CRC Risk.

3.3.1. Occupational Pesticide Exposure and the Association with Colon Cancer, Rectal Cancer, and CRC Risk

Figure 6. Forest Plot of the Associations (effect size: OR, RR, SIR, SMR and 95% CI) Between Occupational Pesticide Exposure and Colon Cancer, Rectal Cancer, or CRC Risk.

3.3.2. Environmental Pesticide Exposure and the Association with Colon Cancer, Rectal Cancer, and CRC Risk In addition to occupational exposure, there were other populations environmentally exposed to pesticides,

3.3.3. Discussion of at-risk Populations’ Pesticide Exposure and Association with Colon Cancer, Rectal Cancer, and CRC Risk

3.4. Comparison to Past Review Articles

3.5. Limitations of this Systematic Review

4. Conclusions

Highlights.

Acknowledgements

Abbreviations:

Footnotes

References

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