一项针对男性农民的研究中有机氯农药的使用与Y染色体镶嵌性缺失
Organochlorine pesticide use and mosaic loss of chromosome Y in a study of male farmers.
作者信息
Hurwitz Lauren M, Chang Vicky C, Beane Freeman Laura E, Machiela Mitchell J, Zhou Weiyin, Andreotti Gabriella, Parks Christine G, Sandler Dale P, Rothman Nathaniel, Berndt Sonja I, Hofmann Jonathan N, Koutros Stella
机构信息
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
出版信息
Environ Res. 2025 Jul 15;277:121539. doi: 10.1016/j.envres.2025.121539. Epub 2025 Apr 3.
BACKGROUND
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.
METHODS
This investigation included 1653 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.
RESULTS
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.
CONCLUSIONS
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.
背景
有机氯（OC）杀虫剂是一类环境持久性化学物质，与包括非霍奇金淋巴瘤和前列腺癌在内的多种癌症风险相关。体外和动物研究表明，某些有机氯可能具有基因毒性，但人类证据有限。Y染色体镶嵌性缺失（mLOY）是基因毒性和基因组不稳定的标志物，与某些癌症有关，可能反映农药暴露的中间效应。我们研究了男性农民循环血液中有机氯使用与mLOY之间的关联。
方法
这项调查纳入了农业健康研究子队列“农业暴露与效应生物标志物研究”中来自爱荷华州和北卡罗来纳州的1653名男性农民。通过问卷调查得出七种有机氯（滴滴涕、林丹、艾氏剂、狄氏剂、氯丹、七氯、毒杀芬）的曾经使用情况、总使用天数以及强度加权使用天数。我们利用性染色体假常染色体区域的基因分型阵列强度数据检测mLOY。采用逻辑回归估计有机氯使用与mLOY之间的关联，并对预先指定的混杂因素进行调整。按与mLOY相关的因素（年龄、吸烟状况、肥胖）和居住州进行分层分析。
结果
在357名农民（21.6%）中检测到mLOY。我们观察到曾经使用滴滴涕（比值比[OR]=1.44[95%置信区间（CI）=1.08 - 1.92]）和林丹（OR = 1.31[0.99 - 1.73]）与mLOY呈正相关。在非肥胖农民中关联更强（滴滴涕：OR = 1.61[1.12 - 2.33]，交互作用p值 = 0.20；林丹：OR = 1.82[1.28 - 2.59]，交互作用p值<0.01）。对于林丹，在年龄≥70岁的农民（趋势p值 = 0.03）和非肥胖农民（趋势p值 = 0.05）中有暴露 - 反应呈阳性的证据。其他有机氯与mLOY的关联不一致。
结论
滴滴涕和林丹的使用与mLOY相关，特别是在某些农民亚组中（例如非肥胖或年龄≥70岁）。我们的研究结果表明，这些农药可能具有基因毒性作用，并为它们与癌症风险的关联提供了新的机制证据。
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