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.
Highlights
Worldwide, urothelial carcinoma (UC) is the most common malignancy of the genitourinary tract
Our study was adequately powered to test these models, with the exception of the combination of 8-OHdG level and the X-ray repair cross-complementing group 1 (XRCC1) haplotype. This is the first study to simultaneously evaluate the relationships between cigarette smoking status, urinary 8-OHdG levels, polymorphisms of XRCC1 (Arg194Trp) and XRCC1 (Arg399Gln), and UC risk
We showed that former smokers and ever-smokers had a 2- to 3-fold increased risk of UC compared to never-smokers
Summary
Urothelial carcinoma (UC) is the most common malignancy of the genitourinary tract. UC originates from the urothelial epithelium and involves malignances of the renal pelvis, the ureter, the bladder and the urethra. In Taiwan, UC is the 12th most frequently. 015-MY3 (2-3), NSC-97-2314-B-038-015-MY3 (3-3)), and NSC 100-2314-B-038 -026. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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