Association of ABCC4 G559T single nucleotide polymorphism with arsenic-induced precancerous hyperkeratosis

Chronic arsenic toxicity, a global health issue, leads to multiple skin cancers. Only 15–20% of exposed individuals ever develop arsenic-specific skin lesions highlighting the role of genetic polymorphisms in inter-individual susceptibility. Multidrug resistance proteins (MRPs), encoded by ATP binding cassette transporter subfamily C ( ABCC ) genes are demonstrated to efflux arsenic metabolites. MRP4 encoded by ABCC4 is a high-affinity efflux transporter of diglutathionylated monomethyl arsonous acid [MMA(GS) 2 ] and dimethyl arsenic acid (DMA V ).The association of ABCC4 polymorphisms with arsenic-disease susceptibility is unknown. The possible association of five previously characterized non-synonymous ABCC4 SNPs with arsenic-induced premalignant hyperkeratosis was examined in the study. A total of 230 study participants were recruited from the highly arsenic-exposed district of Murshidabad in West Bengal, India (136 cases with arsenic-induced premalignant hyperkeratosis; 94 controls with no arsenic-specific skin lesions). Cases and controls were matched in exposure status and demographic variables apart from age. Exposure assessment was performed by total arsenic content analysis of water and urine, while genotyping was performed employing PCR-Sanger sequencing or PCR-RFLP. Our population was monomorphic for 4 of the 5 SNPs studied. Age-adjusted Odds ratio showed the presence of at least one T allele for ABCC4 codon polymorphism confers protection against premalignant hyperkeratosis [OR (95% CI): 0.994 (0.888–0.998)]. Graphical abstract