DNA Repair Gene Polymorphisms and Susceptibility to Urothelial Carcinoma in a Southeastern European Population

Abstract

Single nucleotide polymorphisms (SNPs) in DNA repair genes may predispose to urothelial carcinoma of the bladder (UCB). This study focused on three specific SNPs in a population with high exposure to environmental carcinogens including tobacco and alcohol. A case-control study design was used to assess for presence of XPC PAT +/−, XRCC3 Thr241Met, and ERCC2 Lys751Gln DNA repair gene SNPs in peripheral blood from patients with UCB and healthy individuals. One hundred patients and equal number of healthy subjects were enrolled. The XPC PAT +/+ genotype was associated with a 2-fold increased risk of UCB (OR = 2.16; 95%CI: 1.14–4; p = 0.01). The −/+ and +/+ XPC PAT genotypes were more frequently present in patients with multiple versus single tumors (p = 0.01). No association was detected between ERCC2 Lys751Gln genotypes/alleles, and risk for developing UCB. Presence of the XRCC3 TT genotype (OR = 0.14; 95%CI:0.07–0.25; p < 0.01) and of the T allele overall (OR = 0.26; 95%CI:0.16–0.41; p < 0.01) conferred a protective effect against developing UCB. The XPC PAT −/+ and XRCC3 Thr241Met SNPs are associated with predisposition to UCB. The XPC PAT −/+ SNP is also an indicator of bladder tumor multiplicity, which might require a more individualized surveillance and treatment.