Cancer
Organochlorine insecticide use and mosaic loss of chromosome Y in a study of male farmers Lauren Hurwitz* Lauren Hurwitz Vicky Chang Laura Beane Freeman Mitchell Machiela Weiyin Zhou Gabriella Andreotti Nathaniel Rothman Sonja Berndt Stella Koutros Jonathan Hofmann
Background: Organochlorine (OC) insecticides are a class of environmentally persistent chemicals linked to risk of several cancers, including prostate cancer and non-Hodgkin lymphoma. In vitro and animal studies suggest some OCs may be genotoxic, but evidence in humans is limited. Mosaic loss of chromosome Y (mLOY) is a marker of genomic instability that has been associated with cancer and may reflect intermediate effects of pesticide exposure. We examined associations between OC use and mLOY in circulating blood of male farmers.
Methods: 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 and intensity-weighted lifetime days of use of 7 OCs were derived from questionnaires. mLOY was detected 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 other mLOY risk factors (age, smoking status, obesity [BMI ≥30 kg/m2]) and state of residence.
Results: mLOY was detected in 357 farmers (22%). We observed positive associations with mLOY for ever use of DDT (OR 1.44 [1.08-1.92]) and lindane (OR 1.30 [0.99-1.72]). Associations were stronger among farmers without obesity (DDT: OR 1.61 [1.12-2.33], p-interaction=0.20; lindane: OR 1.80 [1.26-2.56], p-interaction<0.01). For lindane, there was evidence of exposure-response among farmers ≥70 years of age (p-trend=0.03) and those without obesity (p-trend=0.07). Other OCs were not associated with mLOY overall.
Conclusions: Use of DDT and lindane were associated with mLOY, particularly in certain subgroups of farmers (e.g., non-obese or ≥70 years of age). Our findings suggest that these pesticides could confer genotoxic effects and provide new mechanistic evidence for their associations with cancer risk.