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Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study.

ABSTRACT: Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993-2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Rate ratios and 95% confidence intervals were calculated by using Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer incidence. Three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos (rate ratio (RR) for the highest quartile of exposure (Q4) vs. nonexposed = 1.63, 95% confidence interval (CI): 1.22, 2.17; P(trend) < 0.001); malathion (RR for Q4 vs. nonexposed = 1.43, 95% CI: 1.08, 1.88; P(trend) = 0.04); and terbufos (RR for Q4 vs. nonexposed = 1.29, 95% CI: 1.02, 1.64; P(trend) = 0.03). The organochlorine insecticide aldrin was also associated with increased risk of aggressive prostate cancer (RR for Q4 vs. nonexposed = 1.49, 95% CI: 1.03, 2.18; P(trend) = 0.02). This analysis has overcome several limitations of previous studies with the inclusion of a large number of cases with relevant exposure and detailed information on use of specific pesticides at 2 points in time. Furthermore, this is the first time specific pesticides are implicated as risk factors for aggressive prostate cancer.

SUBMITTER: Koutros S

PROVIDER: S-EPMC3590039 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study.

Koutros Stella S Beane Freeman Laura E LE Lubin Jay H JH Heltshe Sonya L SL Andreotti Gabriella G Barry Kathryn Hughes KH DellaValle Curt T CT Hoppin Jane A JA Sandler Dale P DP Lynch Charles F CF Blair Aaron A Alavanja Michael C R MC

American journal of epidemiology 20121121 1

Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993-2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Rate ratios and 95% confidence intervals were calculated by using Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer incidence. Three organophosphate ...[more]

PMID: 23171882

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Project description:Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation, and the risk of hormone-related cancers. Here, we evaluated whether single-nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide-SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1,444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism or regulation (N?=?1,100), as well as SNPs associated with circulating sex steroid concentrations, as identified by genome-wide association studies (N?=?17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction?=?4.0?×?10-5; q-value?=?0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR?=?0.62 95% CI: 0.41, 0.93) and high use of dicamba (OR?=?0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic and antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.

Project description:Background:Agricultural work and occupational pesticide use have been associated with increased risk of renal cell carcinoma (RCC), the most common form of kidney cancer. However, few prospective studies have investigated links to specific pesticides.Objective:We evaluated the lifetime use of individual pesticides and the incidence of RCC.Methods:We evaluated the associations between intensity-weighted lifetime days (IWDs) of 38 pesticides and incident RCC in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Among 55,873 applicators, 308 cases were diagnosed between enrollment (1993–1997) and the end of follow-up (2014–2015). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounding factors, with lagged and unlagged pesticide exposures.Results:There was a statistically significant increased risk of RCC among the highest users of 2,4,5-T compared with never users [unlagged RRIWD Tertile?3=2.92 (95% CI: 1.65, 5.17; ptrend=0.001)], with similar risk estimates for lagged exposure [20-y lag RRIWD Tertile?3=3.37 (95% CI: 1.83, 6.22; ptrend=0.001)]. In 20-y lagged analyses, we also found exposure–response associations with chlorpyrifos [RRIWD Quartile?4=1.68 (95% CI: 1.05, 2.70; ptrend=0.01)], chlordane [RRIWD Tertile?3=2.06 (95% CI: 1.10, 3.87; ptrend=0.02)], atrazine [RRIWD Quartile?4=1.43 (95% CI: 1.00, 2.03; ptrend=0.02)], cyanazine [RRIWD Quartile?4=1.61 (95% CI: 1.03, 2.50; ptrend=0.02)], and paraquat [RRIWD>Median=1.95 (95% CI: 1.03, 3.70; ptrend=0.04)].Conclusions:This is, to our knowledge, the first prospective study to evaluate RCC risk in relation to various pesticides. We found evidence of associations with RCC for four herbicides (2,4,5-T, atrazine, cyanazine, and paraquat) and two insecticides (chlorpyrifos and chlordane). Our findings provide insights into specific chemicals that may influence RCC risk among pesticide applicators. Confirmation of these findings and investigations of the biologic plausibility and potential mechanisms underlying the observed associations are warranted. https://doi.org/10.1289/EHP6334

Project description:BackgroundThough evidence suggests that some pesticides may have thyroid-disrupting properties, prospective studies of associations between specific pesticides and incident thyroid disease are limited.ObjectiveWe evaluated associations between use of specific pesticides and incident hypothyroidism in private pesticide applicators in the Agricultural Health Study (AHS).MethodsSelf-reported incident hypothyroidism ([Formula: see text] cases) was studied in relation to ever-use and intensity-weighted cumulative days of pesticide use at study enrollment. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CI) using Cox proportional hazards models applied to 35,150 male and female applicators followed over 20 y. All models were stratified by state and education to meet proportional hazards assumptions ([Formula: see text] for age x covariate interactions). Models of pesticides that did not meet proportional hazards assumptions were stratified by median attained age (62 y).ResultsHypothyroidism risk was significantly increased with ever- vs. never-use of four organochlorine insecticides (aldrin, heptachlor, and lindane among participants with attained age [Formula: see text]; chlordane in all participants), four organophosphate insecticides (coumaphos in those [Formula: see text]; diazinon, dichlorvos, and malathion in all participants) and three herbicides (dicamba, glyphosate, and 2,4-D in all participants). HRs ranged from 1.21; 95% CI: 1.04, 1.41 (chlordane) to 1.54; 95% CI: 1.23, 19.4 (lindane in those [Formula: see text]). Hypothyroidism risk was greatest among those with higher intensity-weighted lifetime days of using chlordane, lindane, coumaphos (over age 62), diazinon, permethrin, and 2,4-D.ConclusionsOur findings support associations between exposure to several pesticides and increased hypothyroidism risk. These findings are generally consistent with prior analyses of prevalent hypothyroidism in the AHS. https://doi.org/10.1289/EHP3194.

Dataset Information

Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study.

Publications

Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study.

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