Occupational Exposure to Organophosphate Pesticides, DNA Methylation Alterations, and Cancer Risk Among Farm Workers in Ogun State: An Epigenome-Wide Association Study

Organophosphate (OP) pesticides are among the most widely used agrochemicals in Nigeria, yet evidence linking occupational OP exposure to epigenetic alterations and long-term cancer risk in African farming populations remains non-existent. This doctoral epigenome-wide association study (EWAS) investigated DNA methylation alterations associated with occupational OP exposure and cancer risk pathways among farm workers in Ogun State, South West Nigeria. A nested case-cohort design enrolled 300 farm workers with documented OP exposure and 150 unexposed rural non-farm workers. Urinary diethylphosphate and dimethylphosphate metabolites were measured for exposure quantification. Genome-wide DNA methylation was profiled using Illumina EPIC 850K arrays on peripheral blood lymphocytes. Bioinformatic analysis applied linear regression with robust standard errors, pathway enrichment analysis, and Mendelian randomization for causal inference. A total of 847 differentially methylated positions were identified at a Bonferroni-corrected significance threshold. Pathway analysis revealed enrichment in tumor suppressor gene regulation, DNA damage response, and APC signaling pathways. Differentially methylated regions overlapping cancer-relevant genes including MLH1, PTEN, and CDKN2A were identified in workers with cumulative exposures exceeding 500 exposure-days. Mendelian randomization analysis supported a causal relationship between OP-associated methylation at CDKN2A and colorectal cancer risk. The study provides the first EWAS data on occupational OP exposure from a West African population and recommends biological surveillance programs incorporating epigenetic biomarkers, reduced OP registration approvals, and integrated cancer-occupational health monitoring. Keywords: organophosphate pesticides, epigenome-wide association, DNA methylation, cancer risk, farm workers.