title: Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan.
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.
authors: Genomics Research Center, Academia Sinica, No. 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan.
authors: Ling-I
authors: LI
authors: Hsu
authors: Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei 100, Taiwan ; School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors: Meei-Maan
authors: MM
authors: Wu
authors: Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, No. 291 Zhongzheng Road, Zhonghe District, New Taipei City 23561, Taiwan ; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors: Yuan-Hung
authors: YH
authors: Wang
authors: Genomics Research Center, Academia Sinica, No. 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan.
authors: Cheng-Yeh
authors: CY
authors: Lee
authors: Molecular and Genomic Epidemiology Center, China Medical University Hospital, China Medical University, Taichung 404, Taiwan.
authors: Tse-Yen
authors: TY
authors: Yang
authors: Genomics Research Center, Academia Sinica, No. 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan.
authors: Bo-Yu
authors: BY
authors: Hsiao
authors: Genomics Research Center, Academia Sinica, No. 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan ; Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, 17 Xu-Zhou Road, Taipei 100, Taiwan.
authors: Chien-Jen
authors: CJ
authors: Chen
mesh_terms: D000368:Aged; D001151:Arsenic / Q000633:toxicity; D004781:Environmental Exposure; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D013624:Taiwan; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D001151:Arsenic