EPICENE team, ISPED, U1219 INSERM, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France.
EPICENE team, ISPED, U1219 INSERM, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France; Registre des tumeurs primitives du système nerveux central de la Gironde, ISPED, Centre INSERM U1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France.
Environ Int. 2019 Sep;130:104876. doi: 10.1016/j.envint.2019.05.070. Epub 2019 Jul 22.
Pesticides exposures could be implicated in the excess of Central Nervous System (CNS) tumors observed in farmers, but evidence concerning individual pesticides remains limited. Carbamate derivative pesticides, including herbicides and fungicides (i.e. (thio/dithio)-carbamates), have shown evidence of carcinogenicity in experimental studies in animals. In the French AGRICAN cohort, we assessed the associations between potential exposures to carbamate herbicides and fungicides and the incidence of CNS tumors, overall and by histological subtype.
AGRICAN enrolled 181,842 participants involved in agriculture. Incident CNS tumors were identified by linkage with cancer registries from enrollment (2005-2007) until 2013. Individual exposures were assessed by combining information on lifetime periods of pesticide use on crops and the French crop-exposure matrix PESTIMAT, for each of the 14 carbamate and thiocarbamate herbicides and the 16 carbamate and dithiocarbamate fungicides registered in France since 1950. Associations were estimated using proportional hazard models with age as the underlying timescale, adjusting for gender, educational level and smoking.
During an average follow-up of 6.9 years, 381 incident cases of CNS tumors occurred, including 164 gliomas and 134 meningiomas. Analyses showed increased risks of CNS tumors with overall exposure to carbamate fungicides (Hazard Ratio, HR = 1.88; 95% CI: 1.27-2.79) and, to a lesser extent, to carbamate herbicides (HR = 1.44; 95% CI: 0.94-2.22). Positive associations were observed with specific carbamates, including some fungicides (mancozeb, maneb, metiram) and herbicides (chlorpropham, propham, diallate) already suspected of being carcinogens in humans.
Although some associations need to be corroborate in further studies and should be interpreted cautiously, these findings provide additional carcinogenicity evidence for several carbamate fungicides and herbicides.
农药暴露可能与农民中观察到的中枢神经系统(CNS)肿瘤过多有关,但有关个别农药的证据仍然有限。氨基甲酸酯类农药衍生物,包括除草剂和杀真菌剂(即(硫代/二硫代)氨基甲酸酯),在动物实验研究中显示出致癌性的证据。在法国 AGRICAN 队列中,我们评估了潜在暴露于氨基甲酸酯类除草剂和杀真菌剂与 CNS 肿瘤发生率之间的关联,包括总体发生率和组织学亚型。
AGRICAN 招募了 181842 名参与农业的参与者。通过与癌症登记处的链接,从登记(2005-2007 年)到 2013 年,确定了中枢神经系统肿瘤的发病情况。通过结合关于在作物上使用农药的终生期间的信息和法国自 1950 年以来注册的 14 种氨基甲酸酯和硫代氨基甲酸酯除草剂以及 16 种氨基甲酸酯和二硫代氨基甲酸酯杀真菌剂的法国作物暴露矩阵 PESTIMAT,对个体暴露进行了评估。使用年龄作为基础时间尺度的比例风险模型估计关联,调整性别、教育水平和吸烟。
在平均 6.9 年的随访期间,发生了 381 例中枢神经系统肿瘤的病例,包括 164 例胶质瘤和 134 例脑膜瘤。分析表明,总体暴露于氨基甲酸酯类杀真菌剂(危险比,HR=1.88;95%置信区间:1.27-2.79)和,在较小程度上,暴露于氨基甲酸酯类除草剂(HR=1.44;95%置信区间:0.94-2.22)会增加中枢神经系统肿瘤的风险。与一些已被怀疑对人类具有致癌性的特定氨基甲酸酯,包括一些杀真菌剂(代森锰锌、代森锰、代森联)和除草剂(氯普芬、异丙草胺、敌草快),观察到了阳性关联。
尽管一些关联需要在进一步的研究中证实,并应谨慎解释,但这些发现为几种氨基甲酸酯类杀真菌剂和除草剂提供了额外的致癌性证据。