Table 1:
Studies of arsenic and breast cancer included in our review.
| Author, Year, Place | Study design | Study detail/Population | Collected data | Methods and measuresa | Conclusions |
|---|---|---|---|---|---|
| L. Jouybari et al. (Cancer Management and Research, 2018) [13] | Meta-Analysis | 11 studies from multiple countries | Scalp hair (4), Plasma (1), Toenail (2), and Breast tissue (4) | Standard mean Difference:0.52, 95%CI: −0.12–1.16, p=0.114 | No significant statistical difference in Arsenic status between healthy subjects and breast cancer patients. |
| B. Gamboa-Loira et al. (Environmental Research, 2017) [14] | Meta-Analysis (As and cancer risk) | 1 study on breast cancer from Mexico | Urine | OR for %MMA Q5 vs. Q1=2.63, 95%CI: 1.89–3.66 | Significant positive association between % MMA and breast cancer. |
| N. Khanjani et al. (Reviews on Environmental Health, 2017) [15] | Systematic review | 7 studies from multiple countries | Blood (1), urine (1) urine and Blood (1), Toenail (1), and drinking water (3) | Descriptive | Exposure to As may increase the risk of breast cancer to varying degrees depending on individual/regional exposure patterns and genetic susceptibilities. |
| D.F. Romagnolo et al. (Mol. Nutr. Food Res., 2016) [16] | Systematic review (As and epigenetic alterations) | 4 studies from multiple countries | Blood | Descriptive | Interactions between environmental As exposure and alcohol consumption may interfere with normal folate and B12 metabolism and influence breast cancer risk through hypermethylation of tumor suppressor genes. |
| A.S. Bardach et al. (Science of the Total Environment, 2015) [11] | Systematic review (chronic diseases and Arsenic) | 2 studies on breast cancer from Argentina | Aquifer (1) and groundwater (1) | Descriptive | Higher incidence rate ratio per 100 μg/L increment in iAs concentration for breast cancer. |
| A.J. White et al. (Epidemiology, 2019), USA [17] | Cohort Sister study (2003–2009) | 2,587 incident breast cancer cases among 50,884 breast cancer-free women | The Environmental Protection Agency’s National Air Toxics Assessment database | HR (Q5 vs. Q1)=1.0, 95%CI: 0.9–1.2 | No association between Arsenic exposure and breast cancer. |
| R. Zhang et al. (International Journal of Cancer, 2016), USA [18] | Cohort Nurse’s health study (NHS) (1984–2010) | 8115 incident breast cancer cases among 160,408 women | Validated food frequency questionnaires | Multivariable RRs (≥5 servings/week)=0.95, 95%CI: 0.88–1.03 | Long-term consumption of total rice, white rice, or brown rice was not associated with risk of developing breast cancer. |
| R. Liu et al. (Epidemiology, 2015), USA, California [19] | Cohort California Teacher’s study (1995–1996) | 5361 incident breast cancer cases among 112,379 women free of breast cancer living at a California address | Ambient air | HR (Q5 vs. Q1)=1.7, 95%CI: 1.1–2.5 | Long-term, low-dose exposure to iAs may be a risk factor for breast cancer. |
| K.M. O’Brien et al. (American Journal of Epidemiology, 2019), USA [20] | Case-control Sister (2003–2009) and Two sister (2008–2010) studies | 1,217 disease-discordant sister pairs among 50,884 Participants aged 35–74 years | Toenail | OR (Q4 vs. Q1)=1.07, 95%CI: 0.72–1.57 | Little evidence to support a positive association between young-onset breast cancer and exposure to As. |
| B. Gamboa-Loira et al. (Environ Toxicol Pharmacol, 2017), Mexico [21] | Case-control Population-based (Northern Mexico) | 1016 breast cancer cases and 1028 healthy controls | Urine | Interaction p=0.0002 for MTR c.2756A>G polymorphism and % DMA | MTR c.2756A>G polymorphism may confer protection for breast cancer associated with iAs exposure. |
| G. Michel-Ramirez et al. (Journal of Applied Toxicology, 2020), Mexico [22] | Cross-sectional | 182 women >18 years (77 breast cancer cases and 105 controls) recruited from a clinic (all exposed to As through drinking water) | Blood and urine | Adjusted OR for iAs=1.10, 95%CI: 1.01–1.20, p=0.015 | Urinary levels of iAs were associated with significant increase in risk of breast cancer but no interactions between Yes-associated protein (YAP) gene polymorphisms and As urinary levels were identified. |
| O. Ajayi et al. (Medical Sciences, 2018), Nigeria [23] | Cross-sectional | 79 non-pregnant women 28–80 years of age (52 premenopausal and 27 postmenopausal) recruited from a Clinic | Serum from venous blood | Multiple regression Analysis for As related to TSH in premenopausal ER−: β=−0.305 and PR−: β=−0.304 breast cancer | Arsenic was inversely associated with Thyroid stimulating hormone (TSH) in premenopausal participants with ER− and PR− breast cancer. |
| G. Michel-Ramirez et al. (Journal of Applied Toxicology, 2017), Mexico [24] | Cross-sectional | 120 women (76 newly diagnosed breast cancer cases and 44 controls) from a hospital (all exposed to As from drinking water) | Breast biopsies, urine, and toenails | OR for high cytoplasm YAP expression=0.37, 95%CI: 0.17–0.80, p=0.01 | Significantly lower concentration of cytoplasm Yes-associated protein (YAP) expression in cases suggesting YAP may act as a tumor suppressor. |
| N.S. Joo et al. (Biological Trace Element Research, 2009), Korea [25] | Cross-sectional | 144 women (40 breast cancer cases and 144 body-mass index matched controls) recruited from a hospital | Hair | Comparison of mean As among cases and controls: p<0.001 Association of hair iron level with As: r=−0.537, p<0.001 | Breast cancer patients had higher levels of As in hair compared to healthy controls. Lower hair iron levels among breast cancer cases compared to healthy controls and negative correlation of hair iron with As. |
| K. Schlawicke Engstrom et al. (Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2009), Argentina [26] | Cross-sectional (Northern Argentina) | 104 indigenous women exposed to approximately 200 μg/L of As in drinking water with low %MMA and high % DMA | Urine and blood | Association between urinary metabolite patterns of As and SNPs in three gene groups related to As metabolism | Polymorphisms in AS3MT and in genes involved in one-carbon metabolism and reduction reactions affect As metabolism. |
| D.A. Parodi et al. (Reproductive Toxicology, 2015) [27] | Animal | Pregnant spraguedawley rats on day 7 of gestation | Intra-peritoneal injection of arsenite on days 12 and 17 of gestation and morphological analysis of mammary glands | P<0.05 for all comparisons between case and control rats | In utero exposure to arsenite alters the pre- and post-pubertal development of the mammary gland, and possibly the risk of developing breast cancer. |
| E. Egiebor et al. (International Journal of Environmental Research and Public Health, 2013) [28] | In-vitro | MCF7 breast cancer cell lines exposed to different concentrations of As | Kinetic response of As on MCF7 cells measured by realtime cell electronic sensing (RT-CES) | All concentrations of As induced total cell death, ranging from 5 to 20 h after exposure | As was associated with significant cytotoxicity both in the presence and in the absence of glutathione. |
| L. Smeester et al. (Chemical Research in Toxicology, 2011) [29] | In-vivo/In-silico (Mexico) | 16 individuals (8 with elevated levels of iAs exposure and arsenicosis) | Urine, Blood, and Interactome database | Differences in iAs exposure levels in urine: p<0.001 183 differentially-methylated genes in individuals with high iAs levels (arsenicosis): FDR q value<0.05 | Interactome analysis of 183 genes revealed an interactome of hypermethylated genes enriched for those involved in cancer-associated pathways mediated by p53. Also identified an arsenic-methylated tumor suppressorome made up of 17 known or putative tumor suppressors silenced in human cancers. |
a
Explanation of statistical measures abbreviations: OR, Odds Ratio; 95% CI, 95% Confidence Interval; HR, Hazard Ratio; Q5, Quintile 5 (Highest); Q1, Quantile 1 (Lowest); RR, Relative Risk.