Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
J Natl Cancer Inst. 2023 Apr 11;115(4):394-404. doi: 10.1093/jnci/djac242.
Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study.
This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male nonfarmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α, and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker.
Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs lowest glyphosate quartile; geometric mean ratio = 1.15, 95% confidence interval = 1.03 to 1.28; Ptrend = .02) and MDA (geometric mean ratio = 1.20, 95% confidence interval = 1.03 to 1.40; Ptrend = .06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with statistically significantly increased 8-OHdG and MDA levels. Compared with nonfarmers, we observed elevated 8-iso-prostaglandin-F2α levels among farmers with recent, high past 12-month, or high lifetime glyphosate use.
Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide.
草甘膦是全球应用最广泛的除草剂，在流行病学研究中，其使用与某些血液系统癌症的风险增加有关。动物实验和体外实验表明，草甘膦可能会引起氧化应激，这是致癌物质的一个关键特征；然而，人类群体中的证据仍然很少。我们在农业健康研究的分子流行病学子队列中进行了暴露和效应生物标志物研究，调查了草甘膦暴露与尿液氧化应激生物标志物之间的关系。
这项分析包括 268 名男性农民，他们是根据自我报告的最近和终身职业性草甘膦使用情况选择的，100 名年龄和地理位置匹配的非农民男性作为对照。首次晨尿中的草甘膦和氧化应激生物标志物（8-羟基-2'-脱氧鸟苷[8-OHdG]、8-异前列腺素 F2α 和丙二醛[MDA]）浓度进行了定量。我们进行了多变量线性回归，以评估尿液草甘膦浓度和自我报告的草甘膦使用与每种氧化应激生物标志物之间的关系。
尿液草甘膦浓度与 8-OHdG 水平呈正相关（最高与最低四分位草甘膦浓度相比；几何平均比=1.15，95%置信区间=1.03 至 1.28；Ptrend=0.02）和 MDA（几何平均比=1.20，95%置信区间=1.03 至 1.40；Ptrend=0.06）。在报告最近使用草甘膦的农民中（过去 7 天），前一天的使用也与 8-OHdG 和 MDA 水平的统计学显著增加有关。与非农民相比，我们发现近期、过去 12 个月高或终身使用草甘膦的农民，8-异前列腺素 F2α 水平升高。
我们的研究结果为草甘膦暴露与人类氧化应激之间存在关联的证据增加了份量，这可能为评估这种除草剂的致癌潜力提供信息。
