XRCC1 polymorphisms associated with survival among Chinese bladder cancer patients receiving epirubicin and mitomycin C
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The association between DNA repair gene polymorphisms and bladder cancer risk has been widely studied. However, only few studies have examined the correlation between bladder cancer and instillation agent sensitivity. The aim of this study was to examine the association between polymorphisms of DNA repair genes, namely X-ray repair cross-complementing group I (XRCC1) rs2854509 and rs3213255, and bladder cancer recurrence risk. We recruited 244 patients (130 treated with epirubicin and 114 treated with mitomycin C). Genomic DNA was used to examine the XRCC1 rs2854509 and rs3213255 genotypes by Taqman PCR analysis. Combination analysis of XRCC1 rs2854509 and rs3213255 and examination of XRCC1 diplotypes were performed to reveal possible correlations. The rs2854509 CC and rs3213255 TT genotypes conferred shorter survival times than the rs2854509 AC/AA and rs3213255 CC/CT genotypes in patients treated with epirubicin, but not in those treated with mitomycin C (MMC) in adjusted models [hazard ratio (HR) = 0.23, 95 % confidence interval (CI) = 0.10–0.53 for rs2854509 AC + AA compared with CC; HR = 0.17, 95 % CI = 0.06–0.46 for rs3213255 CC + CT compared with TT]. Combination analysis showed significantly increased recurrence-free survival (RFS) among patients simultaneously carrying the rs2854509 AC/AA and rs3213255 CC/CT genotypes with an HR of 0.15 (95 % CI = 0.05–0.45) compared to those carrying other genotypes. Diplotype analysis demonstrated that the A-C/C-T diplotype is associated with a lower risk of recurrence compared with the common wild C-T/C-T diplotype (HR = 0.17, 95 % CI = 0.06–0.51). Our results suggest that the rs2854509 CC and rs3213255 TT genotypes confer higher sensitivity to epirubicin instillation. Moreover, the A-C/C-T diplotype presents significantly lower recurrence risk than other diplotypes.
KeywordsBladder cancer XRCC1 Epirubicin Mitomycin C Chemosensitive
This work was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Program for Development of Innovative Research Team in the First Affiliated Hospital of Nanjing Medical University, Provincial Initiative Program for Excellency Disciplines of Jiangsu Province and the National Natural Science Foundation of China (grant numbers 81171963 and 81201571).
Conflicts of interest
- 1.Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA 2014;64:9–29.Google Scholar
- 7.Sylvester RJ, Oosterlinck W, van der Meijden AP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol. 2004;171:2186–90. quiz 2435.CrossRefPubMedGoogle Scholar
- 8.Przybylowska-Sygut K, Stanczyk M, Kusinska R, Kordek R, Majsterek I. Association of the Arg194Trp and the Arg399Gln polymorphisms of the XRCC1 gene with risk occurrence and the response to adjuvant therapy among polish women with breast cancer. Clin Breast Cancer. 2013;13:61–8.CrossRefPubMedGoogle Scholar