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PLoS One. 2015 May 4;10(5):e0124066. doi: 10.1371/journal.pone.0124066. eCollection 2015.

XRCC1 Polymorphisms and Urinary 8-Hydroxydeoxyguanine Levels Are Associated with Urothelial Carcinoma.

Author information

1
School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
2
Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
3
Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan.
4
Department of Chinese Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
5
Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, Taipei, Taiwan; Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
6
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.

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 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.

PMID:
25938407
PMCID:
PMC4418762
DOI:
10.1371/journal.pone.0124066
[Indexed for MEDLINE]
Free PMC Article

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