XRCC1 Polymorphisms and urinary 8-hydroxydeoxyguanine levels are associated with urothelial carcinoma
Journal
PLoS ONE
Journal Volume
10
Journal Issue
5
Pages
e0124066
Date Issued
2015
Author(s)
Abstract
The aim of this study was to examine the associations between the combined effects of urinary 8-Hydroxydeoxyguanine (8-OHdG) level and polymorphisms of XRCC1 Arg194Trp and XRCC1 Arg399Gln on the risk of urothelial carcinoma (UC). We conducted a hospitalbased case-control study that included 168 cases of UC and 336 age- and gender-matched healthy controls. We used polymerase chain reaction and restriction fragment length polymorphism analyses to examine the genotypes of XRCC1 Arg194Trp and XRCC1 Arg399Gln. We used a competitive in vitro enzyme-linked immunosorbent assay to determine urinary 8-OHdG levels. The XRCC1 399 Gln/Gln genotype and the XRCC1194 Arg/ Arg genotype were positively correlated to UC (OR [95%CI] = 2.27 [1.20-4.27] and 1.59 [1.06 -2.36], respectively). Urinary 8-OHdG levels were associated with UC in a dose-dependent manner. Participants with the XRCC1 (Arg399Gln) Gln/Gln genotype or the G-C/AC haplotype of XRCC1 and a high urinary 8-OHdG level had a significantly higher risk of UC than those with the Arg/Arg + Arg/Gln genotype or the G-T haplotype and a low urinary 8- OHdG level. This is the first study to investigate the combined effect of urinary 8-OHdG level and XRCC1 polymorphisms on UC risk. The findings are especially meaningful for participants with XRCC1 399Gln or XRCC1 Arg194 genotypes and a high urinary 8-OHdG level, since these variables are associated with an increased risk of UC. ? 2015 Chiang et al.
SDGs
Other Subjects
2 aminopurine; 8 hydroxydeoxyguanine; arsenic; unclassified drug; XRCC1 protein; 8-oxo-7,8-dihydrodeoxyguanine; DNA binding protein; guanine; X-ray repair cross complementing protein 1; adult; Article; cancer risk; case control study; controlled study; enzyme linked immunosorbent assay; female; genetic polymorphism; genotype; haplotype; human; major clinical study; male; polymerase chain reaction; questionnaire; restriction fragment length polymorphism; Taiwan; transitional cell carcinoma; XRCC1 gene; adverse effects; analogs and derivatives; cancer grading; cancer staging; demography; genetic predisposition; genetics; middle aged; pathology; risk factor; single nucleotide polymorphism; smoking; urinary tract tumor; urine; urothelium; Case-Control Studies; Demography; DNA-Binding Proteins; Female; Genetic Predisposition to Disease; Guanine; Haplotypes; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Polymorphism, Single Nucleotide; Risk Factors; Smoking; Urologic Neoplasms; Urothelium
Publisher
Public Library of Science
Type
journal article