XRCC1 Polymorphisms and Urinary 8-Hydroxydeoxyguanine Levels Are Associated with Urothelial Carcinoma.
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 hospital-based 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 XRCC1 194 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/A-C 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.
School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
Chien-I
CI
Chiang
Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Ya-Li
YL
Huang
Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan.
Chao-Yuan
CY
Huang
Department of Chinese Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
Horng-Sheng
HS
Shiue
School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
Wei-Jen
WJ
Chen
Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan.
Yeong-Shiau
YS
Pu
Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan; Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Ying-Chin
YC
Lin
Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
Yu-Mei
YM
Hsueh
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D003710:Demography; D005260:Female; D020022:Genetic Predisposition to Disease; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000652:urine*; D019459:Urothelium / Q000473:pathology*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine