Organochlorine pesticide use and mosaic loss of chromosome Y in a study of male farmers.

in Environmental research by Lauren M Hurwitz, Vicky C Chang, Laura E Beane Freeman, Mitchell J Machiela, Weiyin Zhou, Gabriella Andreotti, Christine G Parks, Dale P Sandler, Nathaniel Rothman, Sonja I Berndt, Jonathan N Hofmann, Stella Koutros

TLDR

  • The study found an association between the use of DDT and lindane and mosaic loss of the Y chromosome (mLOY) in male farmers, suggesting potential genotoxic effects and increased cancer risk.

Abstract

Organochlorine (OC) insecticides are a class of environmentally persistent chemicals linked to risk of several cancers, including non-Hodgkin lymphoma and prostate cancer. In vitro and animal studies suggest some OCs may be genotoxic, but evidence in humans is limited. Mosaic loss of the Y chromosome (mLOY) is a marker of genotoxicity and genomic instability that has been associated with certain cancers and may reflect intermediate effects of pesticide exposure. We examined associations between OC use and mLOY in circulating blood of male farmers. This investigation included 1,653 male farmers from Iowa and North Carolina in the Biomarkers of Exposure and Effect in Agriculture study, a subcohort of the Agricultural Health Study. Ever use, total lifetime days, and intensity-weighted lifetime days of use of seven OCs (DDT, lindane, aldrin, dieldrin, chlordane, heptachlor, toxaphene) were derived from questionnaires. We detected mLOY using genotyping array intensity data in the pseudoautosomal regions of the sex chromosomes. Logistic regression was used to estimate associations between OC use and mLOY, adjusted for pre-specified confounders. Stratified analyses were performed by factors associated with mLOY (age, smoking status, obesity) and state of residence. mLOY was detected in 357 farmers (21.6%). We observed positive associations with mLOY for ever use of DDT (OR=1.44 [95% CI=1.08-1.92]) and lindane (OR=1.31 [0.99-1.73]). Associations were stronger among farmers without obesity (DDT: OR=1.61 [1.12-2.33], p-interaction=0.20; lindane: OR=1.82 [1.28-2.59], p-interaction<0.01). For lindane, there was evidence of a positive exposure-response among farmers ≥70 years of age (p-trend=0.03) and those without obesity (p-trend=0.05). Other OCs were not consistently associated with mLOY. Use of DDT and lindane was associated with mLOY, particularly in certain subgroups of farmers (e.g., non-obese or age ≥70 years). Our findings suggest that these pesticides could confer genotoxic effects and provide new mechanistic evidence for their associations with cancer risk.

Overview

  • The study examines the association between the use of organochlorine (OC) insecticides and mosaic loss of the Y chromosome (mLOY) in male farmers.
  • The study included 1,653 male farmers from Iowa and North Carolina, and used data from questionnaires to determine OC use and genotyping array intensity data to detect mLOY.
  • The primary objective of the study is to investigate the potential genotoxic effects of OC insecticides and their association with cancer risk.

Comparative Analysis & Findings

  • The study found positive associations between mLOY and the use of DDT and lindane, with stronger associations among farmers without obesity.
  • The association between lindane use and mLOY was stronger among farmers ≥70 years of age and those without obesity.
  • No consistent associations were found between mLOY and use of other OCs.

Implications and Future Directions

  • The study's findings suggest that DDT and lindane could confer genotoxic effects and provide new mechanistic evidence for their associations with cancer risk.
  • Future studies should investigate the potential mechanisms by which OC use is associated with mLOY and cancer risk.
  • The findings also highlight the need for continued monitoring of pesticide use and exposure levels in agricultural populations.
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