GSTM1 Genotype Modifies the Association Between Total Urinary Arsenic and the Oxidative Stress Biomarker 8-OHDG

Abstract

ISEE-160 Objective: Chronic exposure to arsenic has been associated with several human diseases. Although widely studied, the mechanism of arsenic toxicity is not fully understood. Oxidative stress is one proposed mechanism for arsenic carcinogenesis. Material and Methods: The association between arsenic exposure and the oxidative stress biomarker, 8-hydroxy-2′-deoxyguanosine (8-OHdG) was investigated among a cohort of 97 women exposed to a wide range of arsenic in their drinking water. Arsenic exposure was measured using 3 media: urine, toenails, and drinking water. Urine samples were collected in triplicate on consecutive days. Data were analyzed using random effects Tobit regression to account for repeated measures and 8-OHdG values below the limit of detection. Results: No associations between 8-OHdG and total urinary arsenic, toenail arsenic, or drinking water arsenic were observed. However, a significant gene-environment interaction was found. Total urinary arsenic was positively associated with 8-OHdG in women with the GSTM1 null genotype but not in women with GSTM1 wild type. Among women with GSTM1 null, a comparison of the second, third, and fourth quartiles of total urinary arsenic to the first quartile resulted in β-values of 0.87 (95% CI 0.31–1.44), 1.04 (95% CI 0.43–1.66), and 0.95 (95% CI 0.39–1.51) in logged 8-OHdG, respectively. Among women with GSTM1 wild type, a comparison of the second, third, and fourth quartiles of total urinary arsenic to the first quartile resulted in β-values of −0.11 (95% CI −0.43 to 0.21), −0.04 (95% CI −0.39 to 0.31), and −0.07 (95% CI −0.49 to 0.34), respectively. Conclusions: These results suggest that arsenic is associated with the generation of oxidative stress for individuals with the GSTM1 null genotype and further underscore the importance of considering genetic susceptibility in arsenic toxicity.