Clément Piel1, Camille Pouchieu2, Camille Carles3, Béatrix Béziat1, Mathilde Boulanger4, Mathilde Bureau1, Amandine Busson4, Anne Grüber2, Yannick Lecluse4, Lucile Migault1, Marine Renier4, Virginie Rondeau1, Xavier Schwall1, Séverine Tual4, Lebailly Pierre4, Isabelle Baldi5. 1. EPICENE team, ISPED, U1219 INSERM, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France. 2. 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. 3. EPICENE team, ISPED, U1219 INSERM, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France; CHU de Bordeaux, Service de Médecine du Travail et Pathologies Professionnelles, Bordeaux, France. 4. INSERM, U1086 Anticipe Axe Cancers et Préventions, Caen, France; Université de Caen Normandie, Caen, France; Centre de Lutte Contre le Cancer François Baclesse, Caen, France. 5. 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; CHU de Bordeaux, Service de Médecine du Travail et Pathologies Professionnelles, Bordeaux, France. Electronic address: isabelle.baldi@u-bordeaux.fr.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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