The Dose-response Relationship Between Urinary Arsenic Metabolites and Skin Lesions Using a Pathway Approach

Abstract

S-29B7-2 Background/Aims: Inorganic arsenic (As) is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Limited evidence suggests that an individual's ability to fully metabolize MMA to DMA influences susceptibility to As-induced health effects including cancer. A case-control study conducted in Bangladesh (2001–2003) was used to evaluate the association between metabolism and skin lesions, an early symptom of As toxicity. Methods: A subset of individuals diagnosed with keratosis, melanosis, Bowen disease, or squamous cell carcinoma (n = 881) and individuals without these conditions (n = 868) were used in this analysis. The percentage of each urinary As metabolite was log10 transformed and used as a biomarker of methylation capacity. A novel pathway analysis was used to simultaneously evaluate the association between all urinary arsenic metabolites and the odds of skin lesions using PROC CALIS and Mplus. Additional covariates, including drinking water arsenic, age, creatinine, sex, education, chewing betel nut, and body mass index were also included as covariates. Results: The path analysis explained 44%, 13%, and 8% of the variance in %DMA, %MMA, and %iAs, respectively. We found that the odds of skin lesions was significantly associated with log10%MMA (ORadj: 1.62; 95% confidence interval [CI]: 1.07, 2.47) but not log10%iAs (ORadj: 1.20, 95% CI: 0.78, 1.84) nor log10%DMA (ORadj: 1.46, 95% CI: 0.36, 5.89). Conclusion: This analysis confirmed that individuals who excrete higher levels of MMA have a greater risk of skin lesions while adequately controlling for current arsenic exposure, all urinary arsenic metabolites, and other risk factors.