Abstract
BackgroundThe International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy.MethodsThe Italian Gene-Environment Interactions in Lymphoma Etiology (ItGxE) study took place in 2011–17 in six Italian centres. Overall, 867 incident lymphoma cases and 774 controls participated in the study. Based on detailed questionnaire information, occupational experts classified duration, confidence, frequency, and intensity of exposure to glyphosate for each study subject. Using unconditional regression analysis, we modelled risk of major lymphoma subtypes associated with exposure to glyphosate adjusted by age, gender, education, and study centre.ResultsVery few study subjects (2.2%) were classified as ever exposed to glyphosate. Risk of follicular lymphoma (FL) was elevated 7-fold in subjects classified as ever exposed to glyphosate with medium-high confidence, 4.5-fold in association with medium-high cumulative exposure level, 12-fold with medium-high exposure intensity, and 6-fold with exposure for 10 days or more per year. Significant upward trends were detected with all the exposure metrics, but duration. The overall p-value for an upward trend with four independent metrics was 1.88 × 10− 4. There was no association with risk of lymphoma (any subtype), Non Hodgkin Lymphoma, B-cell lymphoma, or the major lymphoma subtypes other than FL.ConclusionsOur findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen.
Highlights
The International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen
In 2017, the International Agency for Research on Cancer (IARC) classified glyphosate as a probable human carcinogen (Group 2A), as a result of its unequivocal evidence of carcinogenicity in experimental animals, the limited evidence from epidemiological studies, and the robust evidence of human pertinence of the carcinogenic mechanisms identified in cell cultures [4]
Four metanalyses of casecontrol studies conducted in the U.S.A. and Europe consistently showed a moderate increase in risk of nonHodgkin lymphoma (NHL) [5,6,7,8] and of the two major lymphoma subtypes, chronic lymphocytic leukaemia (CLL) and diffuse large B cell lymphoma (DLBCL) [7], among subjects who reported using it two or more days per year
Summary
The International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy. In 2017, the International Agency for Research on Cancer (IARC) classified glyphosate as a probable human carcinogen (Group 2A), as a result of its unequivocal evidence of carcinogenicity in experimental animals, the limited evidence from epidemiological studies, and the robust evidence of human pertinence of the carcinogenic mechanisms identified in cell cultures [4]. The IARC Working Group observed that mechanistic studies documented two out of 10 characteristics of experimental carcinogens as an effect of glyphosate, namely genotoxicity and induction of oxidative stress [4]. The IARC decision prompted a vigorous international debate, fed in part by the different interpretation of the same findings [9], and in part by differences in the main scope of regulatory agencies, and their classification criteria in respect to the IARC hazard assessment
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