title: Polymorphisms of human 8-oxoguanine DNA glycosylase 1 and 8-hydroxydeoxyguanosine increase susceptibility to arsenic methylation capacity-related urothelial carcinoma.
abstract: Arsenic causes oxidative stress in cultured animal and human cells, and it is a well-documented human carcinogen. We conducted a hospital-based case-control study including 167 cases of urothelial carcinoma (UC) and 334 age- and gender-matched healthy controls to evaluate the relationships between urinary arsenic profiles, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels, and human 8-oxoguanine DNA glycosylase (hOGG1) genotypes and UC. The urinary arsenic species were analyzed by high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Genotyping for hOGG1 (Ser326Cys) and hOGG1 (-15C>G) was performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Urinary 8-OHdG was measured with high-sensitivity enzyme-linked immunosorbent assay kits. The results indicated that the hOGG1 326 Cys/Cys genotype and the hOGG1 -15C>G G/G genotype were associated with an increased risk of UC (OR [95 % CI] 1.57 [1.04-2.35] and 1.57 [1.04-2.35], respectively). Participants with high urinary total arsenic, regardless of the haplotype of hOGG1 Ser326Cys and the -15C>G polymorphism, had significantly higher urinary 8-OHdG compared to participants with low urinary total arsenic. This is the first study to investigate the joint effects of high urinary total arsenic or inefficient arsenic methylation capacity indices, and the high-risk G-G haplotype of hOGG1 on the risk of UC. The findings are especially meaningful for participants with risk factors such as high urinary total arsenic, inefficient arsenic methylation indices, high urinary 8-OHdG, and the high-risk G-G haplotype of hOGG1 which are all associated with an increased UC risk.
authors.affiliation: Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan.
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
authors.affiliation: Department of Chinese Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Horng-Sheng
authors.initials: HS
authors.lastname: Shiue
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan.|Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.|Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Lin
authors.affiliation: School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan. ymhsueh@tmu.edu.tw.|Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei 110, Taiwan. ymhsueh@tmu.edu.tw.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Hsueh
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D001151:Arsenic / Q000633:toxicity* / Q000652:urine; D002274:Carcinogens, Environmental / Q000378:metabolism / Q000633:toxicity*; D002277:Carcinoma / Q000139:chemically induced* / Q000235:genetics / Q000652:urine; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics*; D003627:Data Interpretation, Statistical; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008745:Methylation; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014571:Urologic Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000652:urine
chemical_list: D002274:Carcinogens, Environmental; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D003849:Deoxyguanosine; D001151:Arsenic
keywords: 8-Hydroxydeoxyguanosine; 8-Oxoguanine DNA glycosylase; Arsenic; Haplotype; Methylation; Urothelial carcinoma