Genetic Variants in One-carbon Metabolism and DNA Repair Genes Modify the Association between Arsenic and Skin Lesions in Bangladesh

Abstract

Background: Chronic arsenic exposure is associated with skin lesions but the role of genetic susceptibility remains unclear. Aims: To investigate association between single nucleotide polymorphisms (SNPs) in inflammation, one-carbon metabolism and skin cancer genes and skin lesions. Methods: A case-control study was conducted in a population of 540 skin lesion cases and 400 controls in Pabna, Bangladesh in 2001. Thirty-eight SNPs were analyzed at the gene-set level for their association with skin lesions using SNP-set Kernel Association Test (SKAT) adjusting for arsenic exposure measured in water and toenails. Logistic regression was used to estimate the interaction between SNPs and arsenic on risk of skin lesions. Results: Inflammation and one-carbon metabolism gene-sets were significantly associated with skin lesions (P = 0.03), after adjusting for water arsenic and other covariates. Two SNPs rs2278952 (PEMT, P for interaction = 0.003) and rs2228000 (XPC, P for interaction = 0.005) significantly modified the association between arsenic and skin lesions after adjusting for multiple comparisons. Similar results were observed with toenail arsenic. Conclusions: Genetic variants in one-carbon metabolism and DNA repair genes influence susceptibility of arsenic-induced skin lesions.