title: XRCC1 polymorphisms associated with survival among Chinese bladder cancer patients receiving epirubicin and mitomycin C.
abstract: 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.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, People's Republic of China, dengxiaheng@163.com.
authors.forename: Xiaheng
authors.initials: X
authors.lastname: Deng
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.forename: Yidong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Ruizhe
authors.initials: R
authors.lastname: Zhao
authors.forename: Xuzhong
authors.initials: X
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
mesh_terms: D000368:Aged; D000483:Alleles; D054316:Biomarkers, Pharmacological; D002681:China; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D054316:Biomarkers, Pharmacological; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D015251:Epirubicin; D016685:Mitomycin