Meta-analysis of case-control studies to examine the relationship between occupational pesticide exposure and risk of acute myeloid leukemia.

Abstract

7540 Background: Occupational pesticide exposure (OPE) is associated with the risk of developing lymphoid malignancies, but less information is available on large cohorts about the risk of occurrence of acute myeloid leukemia (AML). To answer this question, we performed a meta-analysis including relevant adult case-control studies which reported OPE. Methods: Following PRISMA and MOOSE guidelines, two investigators performed a systematic search in PubMed and Cochrane databases for case-control studies evaluating the association between OPE and AML between 1946 and August 28, 2018. In order to identify the maximum number of studies, keywords related to demographical, pesticides and chemicals data exposures were used. Studies reporting AML diagnosis based only on death certificates, controls from cancer databases and pediatric cases (<15 years-old) were not included. Statistical analyses were performed with R software and the ‘mefafor’ package. Results: Fifteen studies which included 4,068 AML patients and 250,975 control subjects were included. Using a random effects model, the overall analysis showed a significant adverse association between OPE and AML with OR=1.49 (95%CI: 1.10-2.01), and a significant heterogeneity between studies ( I² =0.73, p<0.001). The robustness was checked after sequential exclusion of one study at a time which did not influence the overall OR estimate. A publication bias underestimating the OR was suggested by an asymmetrical funnel plot. Using trim-and-fill method, hypothetical missing studies were added studies in order to adjust the OR (OR=1.76 [95%CI: 1.30-2.38]. A stratified analysis showed that the association was significant in Asian populations (OR=1.74; 95%CI: 1.32-2.30) and upon exposure to insecticides (OR=1.45; 95%CI: 1.16-1.81), yet partly influenced by other factors, since most of the studies reported unadjusted results (n=8, 53%). Data on biological characteristics were unavailable to stratify patients according to AML molecular or cytogenetic characteristics. Conclusions: From this new extensive review and analysis, it clearly appears that AML should be considered as occupational illness in patients with demonstrated OPE. Further studies will have to focus on the biological effects of individual and pesticides cocktails in order to determine the pathogenesis mechanisms involved in leukemogenesis, and to improve individual protection.