Increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of bladder cancer
BACKGROUND Balance of DNA damage and proper repair plays an important role in progression of bladder cancer. Here we aimed to assess the associations of nineteen polymorphisms from seven DNA repair-associated genes (PRAP1, OGG1, APEX1, MUTYH, XRCC1, XRCC2 and XRCC3) with bladder cancer and their interactions in the disease in a Han Chinese population. METHODOLOGY/PRINCIPAL FINDINGS A chip-based TaqMan genotyping for the candidate genes was performed on 227 bladder cancer patients and 260 healthy controls. APEX1 rs3136817, MUTYH rs3219493, three SNPs (rs3213356, rs25487 and rs1799782) in XRCC1, and three SNPs (rs1799794, rs861531 and rs861530) in XRCC3 showed significant associations with the risk of bladder cancer. In haplotype analysis, elevated risks of bladder cancer were observed in those with either haplotype GT (OR = 1.56, P = 0.003) of APEX1, or GGGTC (OR = 2.05, P = 0.002) of XRCC1, whereas decreased risks were in individuals with either GCGCC (OR = 0.40, P = 0.001), or GCGTT (OR = 0.60, = 0.005) of XRCC1, or CCC (OR = 0.65, P = 0.004) of MUTYH, or TTTAT (OR = 0.36, P = 0.009) of XRCC3. Interaction analysis showed that the two-loci model (rs1799794 and rs861530) was the best with the maximal testing accuracy of 0.701, and the maximal 100% cross-validation consistency (P = 0.001). CONCLUSIONS Polymorphisms and haplotypes of DNA repair genes are associated with the risk of bladder cancer, and of which the SNPs (rs1799794 and rs861530) in XRCC3 gene might be two major loci in relation to the susceptibility to bladder cancer in a northwest Chinese population.