Table 1.
Continued (additional columns).
| Authors | Year | Exposure assessment | Outcome assessment | Investigator blinding | Confounders considered or adjusted | Funding source | Overlap |
|---|---|---|---|---|---|---|---|
| Brown et al.[35] | 1990 | In-person structured interview, including detailed farming and pesticide use history For each pesticide, evaluated ever use, first and last year of use, and personal applying/mixing/handling In 1987, supplemental telephone interview to evaluate usual number of days of pesticide use per year among Iowa subjects who had reported agricultural use of specific pesticides | Diagnostic confirmation by regional pathologists; special review of myelodysplasias by one pathologist co-author | No | Adjusted: vital status, age, state, ever used tobacco daily, first-degree family history of LHC, non-farming job related to leukemia risk in this study, exposure to substances (benzene, naphtha, hair dyes) related to leukemia risk in this study | Partial support from National Institute of Environmental Health Sciences | Brown et al.[32]; Cantor et al.[24]; De Roos et al.[13]; Lee et al.[29] |
| Brown et al.[32] | 1993 | In-person structured interview, including detailed farming and pesticide use history For each pesticide, evaluated ever use, first and last year of use, personal applying/mixing/handling, and use of protective equipment | Diagnostic confirmation by an expert pathologist | No | Adjusted: vital status, age Considered: smoking, education, other factors found not to be confounders of agricultural risk factors | Partial support from National Institute of Environmental Health Sciences | Brown et al.[35]; Cantor et al.[24]; De Roos et al.[13]; Lee et al.[29] |
| Cantor et al.[24] | 1992 | In-person structured interview, including detailed farming and pesticide use history of all subjects who had worked on a farm for ≥ 6 months since age 18 years For each pesticide, evaluated ever use, first and last year of use, method of application, personal applying/mixing/handling, and use of protective equipment | Diagnostic confirmation and morphological classification by panel of 4 experienced regional pathologists | No | Adjusted: vital status, state, age, cigarette smoking status, first-degree family history of LHC, non-farming job related to NHL risk in this study, exposure to hair dyes, exposure to other substances associated with NHL risk in this study Considered: pesticides belonging to other chemical families | Partial support from National Institute of Environmental Health Sciences | Brown et al.[35]; Brown et al.[32]; De Roos et al.[13]; Lee et al.[29] |
| Cocco et al.[18] | 2013 | In-person structured interview, including detailed farming and pesticide use history for all subjects who reported having worked in agriculture For each agricultural job, reported tasks, crops, size of cultivated area, pests treated, pesticides used, crop treatment procedures, use of personal protective equipment, re-entry after treatment, and frequency of treatment in days per year | Histologically or cytologically confirmed cases with central review of slides of ∼20% by an international team of pathologists | No | Adjusted: age, gender, education, study center | European Commission, 5th and 6th Framework Programmes; Spanish Ministry of Health; German Federal Office for Radiation Protection; La Fondation de France; Italian Ministry for Education, University and Research; Italian Association for Cancer Research | None |
| De Roos et al.[13] | 2003 | Telephone interview in Nebraska and Kansas; in-person structured interview in Iowa and Minnesota Nebraska: Question about use of any pesticide, followed by prompting for specific selected pesticides, including years of use and average days per year Iowa and Minnesota: Direct question about a selected use of specific pesticides, including first and last years of use Kansas: Open-ended question about use of pesticides, followed by questions on duration of use and days per year for groups of pesticides but not individual pesticides (with validation study) | Nebraska: Pathology review with histological confirmation and classification including immunologic phenotyping Iowa and Minnesota: Diagnostic confirmation and morphological classification by panel of 4 experienced regional pathologists Kansas: Diagnostic confirmation and classification by panel of 3 pathologists | Yes in Nebraska; no in Iowa, Minnesota, and Kansas | Adjusted: age, study site, other individual pesticides with ≥ 20 users in full study Considered: first-degree family history of LHC, education, smoking | NR; assume National Cancer Institute | Brown et al.[35]; Brown et al.[32]; Cantor et al.[24]; Lee et al.[29] (also Hoar et al.[47]; Hoar Zahm et al.[48]) |
| De Roos et al.[12] | 2005 | Self-administered written questionnaire (with validation study) evaluating detailed use of 22 pesticides for private applicators, 28 pesticides for commercial applicators (ever/never use, frequency, duration, and intensity of use, decade of first use), and ever/never use for additional pesticides up to total of 50, with general information on pesticide application methods, personal protective equipment, pesticide mixing, and equipment repair Additional self-administered take-home questionnaire with further questions on occupational exposures and lifestyle factors | Linkage to state cancer registry files, state death registries, and National Death Index | None | Adjusted: age at enrollment, education, cigarette smoking pack-years, alcohol consumption in past year, first-degree family history of cancer, state of residence Considered (adjusted for MM only): 5 pesticides for which cumulative exposure-days were most highly associated with those for glyphosate (i.e., 2,4-dichlorophenoxyacetic acid, alachlor, atrazine, metolachlor, trifluralin), 5 pesticides for which ever/never use was most highly associated with that for glyphosate (i.e., benomyl, maneb, paraquat, carbaryl, diazinon) | National Cancer Institute, National Institute of Environmental Health Sciences, Environmental Protection Agency, and National Institute for Occupational Safety and Health | Sorahan[26] |
| Eriksson et al.[14] | 2008 | Self-administered mailed questionnaire with additional telephone interview for missing or unclear answers; evaluated occupational exposure to individual pesticides, including number of years, number of days per year, and approximate length of exposure per day | Diagnostic pathological specimens examined and classified by 1 of 5 Swedish expert lymphoma reference pathologists, if not already initially reviewed by one of them; panel review if classification differed from original report | Yes | Adjusted: age, sex, and year of diagnosis or enrollment; other associated agents (4-chloro-2-methyl phenoxyacetic acid, 2,4-dichlorophenoxyacetic acid and/or 2,4,5-trichlorophenoxyacetic acid, mercurial seed dressing, arsenic, creosote, tar) for NHL only | Swedish Council for Working Life and Social Research; Cancer and Allergy Fund; Key Fund; Örebro University Hospital Cancer Fund | None |
| Hardell and Eriksson[27] | 1999 | Self-administered mailed questionnaire with supplemental telephone interview for unclear answers; assessed use of pesticides within different occupations, wet contact if not handling the sprayer, brand names of pesticides, years of exposure, and cumulative days of exposure Exposure excluded 1 year prior to diagnosis or index year | Histopathological diagnosis of NHL reported to regional cancer registries, confirmed by review of pathology reports | Yes | Adjusted: age, county, vital status, year of death if deceased, use of phenoxyacetic acids | Swedish Work Environment Fund, Swedish Medical Research Council, Örebro County Council Research Committee, Örebro Medical Center Research Foundation | Hardell et al.[15] |
| Hardell et al.[15] | 2002 | Self-administered mailed questionnaire with supplemental telephone interview for unclear answers; assessed years and total number of days of occupational exposure to various agents and names of agents Exposure defined as ≥ 1 working day with induction period of ≥ 1 year | Histologically verified NHL; confirmation of hairy-cell leukemia NR | Yes | Adjusted: study, study area, vital status, other associated pesticides (4-chloro-2-methyl phenoxyacetic acid, 2,4-dichlorophenoxyacetic acid + 2,4,5-trichlorophenoxyacetic acid, other herbicides) | Swedish Cancer Research Fund, Swedish Medical Research Council, Örebro County Council Research Committee, Örebro Medical Centre Research Foundation | Hardell and Eriksson[27] Nordström et al.[30] |
| Hohenadel et al.[28] | 2011 | Telephone interview for detailed information on pesticide use in subjects who reported in a self-administered mail questionnaire that they had ≥ 10 hours of pesticide use during their lifetime, plus 15% random sample of subjects with < 10 hours Pesticide interview (with validation study) included a pre-mailed list of specific pesticides (chemical and trade names) with number of days used and number of hours per day at home or work for each pesticide | Diagnostic confirmation based on information, including pathology reports, from cancer registries and hospitals; pathological material reviewed and classified by a reference pathologist; subjects with unavailable pathological material retained in study | No | Adjusted: age, province, use of a proxy respondent Considered: diesel exhaust, ultraviolet radiation, farm animals, chemicals such as benzene, first-degree family history of cancer | Health Canada, British Columbia Health Research Foundation, Centre for Agricultural Medicine at University of Saskatchewan | Kachuri et al.[33]; Karunanayake et al.[31]; McDuffie et al.[16]; Pahwa et al.[34] |
| Kachuri et al.[33] | 2013 | Telephone interview for detailed information on pesticide use in subjects who reported in a self-administered mail questionnaire that they had ≥ 10 hours of pesticide use during their lifetime, plus 15% random sample of subjects with < 10 hours Pesticide interview (with validation study) included a pre-mailed list of specific pesticides (chemical and trade names) with number of days used and number of hours per day at home or work for each pesticide | Diagnostic confirmation based on information, including pathology reports, from cancer registries and hospitals; pathological material reviewed and classified by a reference pathologist (including pathology and tumor tissue slides for 125 [37%] of 342 cases); subjects with unavailable pathological material retained in study | No | Adjusted: age, province, use of a proxy respondent, smoking status, personal history of rheumatoid arthritis, allergies, measles, shingles, or cancer, family history of cancer | Occupational Cancer Research Centre; Cancer Care Ontario; Ontario Workplace Safety and Insurance Board; Canadian Cancer Society, Ontario Division, Mitacs-Accelerate Graduate Research Internship Program | Hohenadel et al.[28]; Karunanayake et al.[31]; McDuffie et al.[16]; Pahwa et al.[34] |
| Karunanayake et al.[31] | 2012 | Telephone interview for detailed information on pesticide use in subjects who reported in a self-administered mail questionnaire that they had ≥ 10 hours/year of cumulative exposure to any combination of herbicides, insecticides, fungicides, fumigants, and algicides Pesticide interview collected information on exposure to individual pesticides, place of pesticide use, year of first use, first year on market, number of years of use, and days per year of use [Note differences from related studies] | Initial diagnosis based on information from cancer registries and hospitals; pathology and tumor tissue slides for 155 of 316 cases reviewed by a reference pathologist who confirmed HL in 150/155 cases, plus 7 cases originally classified as NHL; subjects with unavailable pathological material retained in study | No | Adjusted: age, province, personal history of measles, acne, hay fever, or shingles, first-degree family history of cancer | NR; assume same as in related studies | Hohenadel et al.[28]; Kachuri et al.[33]; McDuffie et al.[16]; Pahwa et al.[34] |
| Kaufman et al.[36] | 2009 | Interview with nurse to assess occupational and non-occupational exposure to pesticides and other potential risk factors | Histologically confirmed leukemia diagnosed within 6 months before current hospital attendance or admission | No | Considered: age, sex, income, use of cellular telephones, benzene and other solvent exposure, occupational and non-occupational pesticide exposure, pesticides used near home, working with power lines, living near power lines, exposure to X-rays, exposure to certain types of electromagnetic fields, use of hair dyes | Thailand Research Fund and Commission on Higher Education | None |
| Lee et al.[29] | 2004 | Telephone interview in Nebraska; in-person structured interview in Iowa and Minnesota Questions included personal handling of groups of pesticides and individual pesticides used on crops or animals, with years of first and last use | Nebraska: Pathology review with histological confirmation and classification including immunologic phenotyping Iowa and Minnesota: Diagnostic confirmation and morphological classification by panel of 4 experienced regional pathologists | Yes in Nebraska; no in Iowa and Minnesota | Adjusted: age, state, vital status Considered: gender, smoking, first-degree family history of LHC, ever having a job correlated with risk of LHC (e.g., painting or welding), use of protective equipment | NR; assume National Cancer Institute | Brown et al.[35]; Brown et al.[32]; Cantor et al.[24]; De Roos et al.[13] (also Hoar Zahm et al.[48]) |
| McDuffie et al.[16] | 2001 | Telephone interview for detailed information on pesticide use in subjects who reported in a self-administered mail questionnaire that they had ≥ 10 hours of pesticide use during their lifetime, plus 15% random sample of subjects with < 10 hours (total = 179 cases, 456 controls with telephone interview) Pesticide interview (with validation study) included a pre-mailed list of specific pesticides (chemical and trade names) with number of days used and number of hours per day at home or work for each pesticide | Diagnostic confirmation from cancer registries and hospitals; pathological material reviewed and classified by a reference pathologist; subjects with unavailable pathological material retained in study | No | Adjusted: age, province, personal history of measles, mumps, cancer, or allergy desensitization shots, first-degree family history of cancer Considered: pesticide exposure, smoking history | Health Canada, British Columbia Health Research Foundation, Centre for Agricultural Medicine at University of Saskatchewan | Hohenadel et al.[28]; Kachuri et al.[33]; Karunanayake et al.[31]; Pahwa et al.[34] |
| Nordström et al.[30] | 1998 | Self-administered mailed questionnaire with supplemental telephone interview for unclear or missing answers; assessed total number of days of occupational exposure to various agents Exposure defined as ≥ 1 working day with induction period of ≥ 1 year | Reported to national cancer registry; further confirmation not described | Yes | Adjusted: age Considered: exposure to animals, herbicides, insecticides, fungicides, impregnating agents, organic solvents, exhausts, or ultraviolet light | Swedish Work Environment Fund, Örebro County Council Research Committee, Örebro Medical Centre Research Foundation. | Hardell et al.[15] |
| Orsi et al.[17] | 2009 | Self-administered written questionnaire with lifetime occupational history, followed by in-person structured interview evaluating non-occupational exposure to pesticides and agricultural questionnaire for subjects who had worked as a farmer or gardener for ≥ 6 months during lifetime Agricultural questionnaire collected data on location of all farms where subject had worked for ≥ 6 months, period of occupation and area, farmer's status at each farm, crops and animal husbandry with mean sizes, all pesticides used on each crop during a given period, whether subject had personally prepared, mixed, or sprayed the pesticide, chemical used, brand name, main use, type of spraying equipment used, annual number and duration of applications, and use of pesticides in farm buildings for animals, grain, hay or straw, or to clear lanes and yards All questionnaires reviewed by an occupational hygienist and an agronomist; repeat telephone interviews conducted to clarify information from 95 (56.8%) of 158 subjects who completed the agricultural questionnaire, not completed by 35 (20.8%) who refused (n = 15), died/were in poor health (n = 10), or could not be contacted (n = 15); all chemicals coded using ad hoc system and classified as definite or possible exposure | All diagnoses cytologically or histologically confirmed and reviewed by a panel of pathologists and hematologists | Yes | Adjusted: age, study center, socioeconomic category Considered: all combinations of pesticide families associated with the LHC subtype considered with a p-value ≤ 0.10, rural/urban status, type of housing, educational level, history of mononucleosis, history of influenza immunization, family history of cancer, skin characteristics, smoking status, and alcohol drinking status | Association pour la Recherche contre le Cancer, Fondation de France, AFSSET, Faberge employees (donation) | None |
| Pahwa et al.[34] | 2012 | Telephone interview for detailed information on pesticide use in subjects who reported in a self-administered mail questionnaire that they had ≥ 10 h of pesticide use during their lifetime, plus 15% random sample of subjects with < 10 h Pesticide interview (with validation study) included a pre-mailed list of specific pesticides (chemical and trade names) with number of days used and number of hours per day at home or work for each pesticide | Diagnostic confirmation based on information, including pathology reports, from cancer registries and hospitals; pathological material reviewed and classified by a reference pathologist (including pathology and tumor tissue slides for 125 [37%] of 342 cases); subjects with unavailable pathological material retained in study | No | Adjusted: age, province, personal history of measles, mumps, allergies, arthritis, or shingles, first-degree family history of cancer | Occupational Cancer Research Centre; Cancer Care Ontario; Ontario Workplace Safety and Insurance Board; Canadian Cancer Society | Hohenadel et al.[28]; Kachuri et al.[33]; Karunanayake et al.[31]; McDuffie et al.[16] |
| Sorahan[26] | 2015 | Self-administered written questionnaire (with validation study) evaluating detailed use of 22 pesticides for private applicators, 28 pesticides for commercial applicators (ever/never use, frequency, duration, and intensity of use, decade of first use), and ever/never use for additional pesticides up to total of 50, with general information on pesticide application methods, personal protective equipment, pesticide mixing, and equipment repair Additional self-administered take-home questionnaire with further questions on occupational exposures and lifestyle factors Missing data classified into “not known/missing” category, with unknown use of 2,4-dichlorophenoxyacetic acid classified with no use and unknown education classified with no education beyond high school due to lack of MM cases in unknown categories | Linkage to state cancer registry files, state death registries, and National Death Index | None | Fully adjusted: age, gender, smoking pack-years, alcohol use in year before enrollment, first-degree family history of cancer, education, use of 2,4-dichlorophenoxyacetic acid, alachlor, atrazine, metolachlor, or trifluralin, ever use of benomyl, maneb, paraquat, carbaryl, or diazinon Intermediate adjusted: age, gender, smoking, alcohol, family history of cancer, education Adjusted in full cohort: age, gender, family history of cancer, education | Monsanto Europe SA/NV | De Roos et al.[12] |
CI: confidence interval; CLL: chronic lymphocytic leukemia; DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; HL: Hodgkin lymphoma; LHC: lymphohematopoietic cancer; LPS: lymphoproliferative syndrome; MM: multiple myeloma; NHL: non-Hodgkin lymphoma; NR: not reported; OR: odds ratio; SLL: small lymphocytic lymphoma.
CI: confidence interval; CLL: chronic lymphocytic leukemia; DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; HL: Hodgkin lymphoma; LHC: lymphohematopoietic cancer; LPS: lymphoproliferative syndrome; MM: multiple myeloma; NHL: non-Hodgkin lymphoma; NR: not reported; OR: odds ratio; SLL: small lymphocytic lymphoma.