Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan
Resource
Biomed Res. Int., ,
Journal
BioMed Research International
Pages
1
Date Issued
2015
Date
2015
Author(s)
Hsu, Ling-I
Wu, Meei-Maan
Wang, Yuan-Hung
Lee, Cheng-Yeh
Yang, Tse-Yen
Hsiao, Bo-Yu
Chen, Chien-Jen
Abstract
Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01-8.83; OR = 2.04, 95% CI = 0.99-4.27; OR = 1.74, 95% CI = 1.00-3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.
SDGs
Other Subjects
arsenic; ATM protein; DNA; EPHX1 protein; glutathione transferase; HO 1 protein; hOGG1 protein; NQO1 protein; reactive oxygen metabolite; unclassified drug; xeroderma pigmentosum group D protein; XRCC1 protein; arsenic; EPHX1 protein, human; epoxide hydrolase; ERCC2 protein, human; glutathione transferase; xeroderma pigmentosum group D protein; Article; cancer risk; controlled study; DNA extraction; DNA repair; environmental exposure; genetic analysis; genetic polymorphism; genetic susceptibility; genotyping technique; heredity; heterozygote; human; major clinical study; risk assessment; skin cancer; skin carcinogenesis; Taiwan; aged; chemically induced; environmental exposure; female; genetic association study; genetics; genotype; male; middle aged; pathology; risk factor; single nucleotide polymorphism; skin tumor; Aged; Arsenic; Environmental Exposure; Epoxide Hydrolases; Female; Genetic Association Studies; Genotype; Glutathione Transferase; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Skin Neoplasms; Taiwan; Xeroderma Pigmentosum Group D Protein