Dataset Information

Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health Study.

ABSTRACT: Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected between 2006 and 2008. Self-reported information, including pesticide use, was collected at three time points: enrollment (1993-1997) and two follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated cumulative use (using data from all three questionnaires), and more recent use (using data from the last follow-up questionnaire). Multivariable linear regression was used to examine the associations between pesticide use (ever, lifetime days, intensity-weighted lifetime days (lifetime days*intensity score)) and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57 pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p-trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were significantly associated with shorter RTL, while increasing lifetime days of alachlor was significantly associated with longer RTL (p-trend=0.03). Only the association with 2,4-D was significant after adjustment for multiple comparisons. Of the 40 pesticides evaluated for recent use, malathion was associated with shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest that leukocyte TL may be impacted by cumulative use and recent use of certain pesticides.

SUBMITTER: Andreotti G

PROVIDER: S-EPMC4510132 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health Study.

Andreotti Gabriella G Hoppin Jane A JA Hou Lifang L Koutros Stella S Gadalla Shahinaz M SM Savage Sharon A SA Lubin Jay J Blair Aaron A Hoxha Mirjam M Baccarelli Andrea A Sandler Dale D Alavanja Michael M Beane Freeman Laura E LE

PloS one 20150721 7

Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected betwee ...[more]

PMID: 26196902

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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.

Project description:BackgroundPesticide exposure is associated with many long-term health outcomes; the potential underlying mechanisms are not well established for most associations. Epigenetic modifications, such as DNA methylation, may contribute. Individual pesticides may be associated with specific DNA methylation patterns but no epigenome-wide association study (EWAS) has evaluated methylation in relation to individual pesticides.ObjectivesWe conducted an EWAS of DNA methylation in relation to several pesticide active ingredients.MethodsThe Agricultural Lung Health Study is a case-control study of asthma, nested within the Agricultural Health Study. We analyzed blood DNA methylation measured using Illumina's EPIC array in 1,170 male farmers of European ancestry. For pesticides still on the market at blood collection (2009-2013), we evaluated nine active ingredients for which at least 30 participants reported past and current (within the last 12 months) use, as well as seven banned organochlorines with at least 30 participants reporting past use. We used robust linear regression to compare methylation at individual C-phosphate-G sites (CpGs) among users of a specific pesticide to never users.ResultsUsing family-wise error rate (p<9×10-8) or false-discovery rate (FDR<0.05), we identified 162 differentially methylated CpGs across 8 of 9 currently marketed active ingredients (acetochlor, atrazine, dicamba, glyphosate, malathion, metolachlor, mesotrione, and picloram) and one banned organochlorine (heptachlor). Differentially methylated CpGs were unique to each active ingredient, and a dose-response relationship with lifetime days of use was observed for most. Significant CpGs were enriched for transcription motifs and 28% of CpGs were associated with whole blood cis-gene expression, supporting functional effects of findings. We corroborated a previously reported association between dichlorodiphenyltrichloroethane (banned in the United States in 1972) and epigenetic age acceleration.DiscussionWe identified differential methylation for several active ingredients in male farmers of European ancestry. These may serve as biomarkers of chronic exposure and could inform mechanisms of long-term health outcomes from pesticide exposure. https://doi.org/10.1289/EHP8928.

Dataset Information

Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health Study.

Publications

Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health Study.

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