Pesticide use and risk of non-Hodgkin lymphoid malignancies in agricultural cohorts from France, Norway and the USA: a pooled analysis from the AGRICOH consortium

Background: Pesticides are commonly used in agriculture, and previous studies endorsed the need to further investigate the possible association between their use and risk of lymphoid malignancies in agricultural workers. Methods: We investigated the relationship of ever use of 14 selected pesticide chemical groups and 33 individual active chemical ingredients with non-Hodgkin lymphoid malignancies (NHL) overall or major subtypes, in a pooled analysis of three large agricultural worker cohorts. Pesticide use was derived from self-reported history of crops cultivated combined with crop-exposure matrices (France and Norway) or self-reported lifetime use of active ingredients (USA). Cox regression models were used to estimate cohortspecific hazard ratios (HRs) and 95% confidence intervals (CIs), which were combined using random effects meta-analysis to calculate meta-HRs. Results: During follow-up, 2430 NHL cases were diagnosed in 316 270 farmers accruing 3 574 815 person-years under risk. Most meta-HRs suggested no association. Moderately elevated meta-HRs were seen for: NHL and ever use of terbufos (meta-HR¼1.18, 95% CI: 1.00–1.39); chronic lymphocytic leukaemia/small lymphocytic lymphoma and deltamethrin (1.48, 1.06–2.07); and diffuse large B-cell lymphoma and glyphosate (1.36, 1.00– 1.85); as well as inverse associations of NHL with the broader groups of organochlorine insecticides (0.86, 0.74–0.99) and phenoxy herbicides (0.81, 0.67–0.98), but not with active ingredients within these groups, after adjusting for exposure to other pesticides. Conclusions: Associations of pesticides with NHL appear to be subtype- and chemicalspecific. Non-differential exposure misclassification was an important limitation, showing the need for refinement of exposure estimates and exposure–response analyses.