Acetanilide herbicide exposure and lymphoid malignancy risk in the French AGRiculture and CANcer cohort

Many studies have reported an elevated risk of specific cancers including lymphoid malignancies (LM) in farmers, particularly those exposed to pesticides. Acetanilides are among the most widely sold herbicides in France. This study evaluated the risk for specific LM subtypes in relation to exposure to acetanilide herbicides in 155,173 individuals enrolled between 2005 and 2007 in the French AGRICAN cohort. Incident LM cases were identified through linkage with French cancer registries from enrollment to December 2017. Exposure to nine acetanilide active ingredients was estimated using the PESTIMAT crop-exposure matrix. Cox models with age as the time scale were used to estimate hazard ratios and 95 % confidence intervals for lifetime exposure, duration and exposure score for each LM subtype. 22,858 acetanilide users and 1,654 LM cases were identified. Among men, an increased risk of multiple myeloma was observed for alachlor, dimethachlor, metolachlor, and napropamide, particularly at low and intermediate exposure scores. Risk was also increased for follicular lymphoma, mature T-cell and natural killer cell lymphoma, lymphoplasmacytic lymphoma and marginal zone lymphoma. We also observed some inverse associations with certain subtype risks such as multiple myeloma for exposure to recent molecules like dimethenamid et dimethenamid-p. Among women, an increased risk of chronic lymphoid leukemia/small lymphocytic lymphoma was observed for exposure to napropamide. This study provides new evidence supporting the role of acetanilides in LM subtype risk.