Polymorphisms of human 8-oxoguanine DNA glycosylase 1 and 8-hydroxydeoxyguanosine increase susceptibility to arsenic methylation capacity-related urothelial carcinoma
Journal
Archives of Toxicology
Journal Volume
90
Journal Issue
8
Pages
1917-1927
Date Issued
2016
Author(s)
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. ? 2015, Springer-Verlag Berlin Heidelberg.
Other Subjects
8 hydroxydeoxyguanosine; 8 hydroxyguanine; 8 oxoguanine DNA glycosylase 1; arsenic; DNA glycosyltransferase; unclassified drug; 8-oxo-7-hydrodeoxyguanosine; arsenic; carcinogen; deoxyguanosine; DNA glycosyltransferase; oxoguanine glycosylase 1, human; analytical equipment; Article; atomic absorption spectrometry; cancer risk; cancer susceptibility; controlled study; DNA polymorphism; gene; genetic association; genetic risk; genetic susceptibility; genotype; haplotype; high performance liquid chromatography; high risk population; hOGG1 gene; hospital based case control study; human; major clinical study; methylation; polymerase chain reaction; priority journal; risk assessment; structured questionnaire; transitional cell carcinoma; urine level; analogs and derivatives; carcinoma; case control study; chemically induced; genetic predisposition; genetics; metabolism; methylation; risk factor; single nucleotide polymorphism; statistical analysis; urinary tract tumor; urine; Arsenic; Carcinogens, Environmental; Carcinoma; Case-Control Studies; Data Interpretation, Statistical; Deoxyguanosine; DNA Glycosylases; Genetic Predisposition to Disease; Genotype; Humans; Methylation; Polymorphism, Single Nucleotide; Risk Factors; Urologic Neoplasms
Publisher
Springer Verlag
Type
journal article