title: High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study.
abstract: Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P < 0.01) and for the mean across the CpGs measured in the GSTp1 promoter (P < 0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; P = 0.03), CpG3 (chr10:131,265,810; P = 0.05), and the mean across CpGs measured in the MGMT promoter (P = 0.03) among applicators >59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19-29, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Preventive Medicine, Uniformed Services University, Bethesda, Maryland.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Rusiecki
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Beane Freeman
authors.affiliation: Department of Epidemiology and Environmental Health, State University of New York, Buffalo, New York.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Bonner
authors.affiliation: Department of Preventive Medicine, Uniformed Services University, Bethesda, Maryland.
authors.forename: Melannie
authors.initials: M
authors.lastname: Alexander
authors.affiliation: Department of Preventive Medicine, Uniformed Services University, Bethesda, Maryland.
authors.forename: Ligong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Andreotti
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Barry
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
authors.forename: Lee E
authors.initials: LE
authors.lastname: Moore
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom.
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
authors.forename: Freya
authors.initials: F
authors.lastname: Kamel
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Alavanja
authors.affiliation: Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Hoppin
authors.affiliation: Harvard School of Public Health, Harvard University, Boston, Massachusetts.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D004247:DNA / Q000097:blood; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D000067565:Farmers; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D007484:Iowa; D008297:Male; D009657:North Carolina; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D016272:Occupational Health; D010575:Pesticides / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000395:Air Pollutants, Occupational; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D010575:Pesticides; D025521:Tumor Suppressor Proteins; D004247:DNA; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D045643:DNA Repair Enzymes
keywords: Agricultural Health Study; DNA methylation; epigenetics; exposure; pesticides