AB161. Rottlerin-induced autophagy leads to the apoptosis in bladder cancer cells

Objective: 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) and their interactions with bladder cancer in a Han Chinese population. Methods: A case-control study including 227 bladder cancer patients and 260 healthy controls was conducted. A chip-based TaqMan genotyping was performed for the candidate genes. Results: APEX1 rs3136817, MUTYH rs3219493, three SNPs (rs3213356, rs2023614 and rs1799782) in XRCC1, and two SNPs (rs1799794 and rs861530) in XRCC3 showed significant associations with the risk of bladder cancer. After the Bonferroni correction, these associations were still significant. In haplotype analysis, Haplotype GT in APEX1 had a higher frequency in cases than in controls (P=0.003). Haplotype GGGTC in XRCC1 also had a higher frequency in cases than in controls (P=0.002), whereas haplotypes GCGCC and GCGTT in XRCC1 had lower frequencies in cases (P=0.001; P=0.005, respectively). Haplotype CCC in MUTYH and TTTAC in XRCC3 had a lower frequency in cases (P=0.004; P=0.009, respectively). In further interaction analysis, the five locus model including rs3218454, rs1799794, rs861537, rs861531 and rs861530 emerged as the best multifactor dimensionality reduction (MDR) model in homologous recombination repair (HRR) genes with the maximal testing accuracy of 0.701 and the maximal crossvalidation consistency of 10 out of 10 (P=0.001). Conclusions: Our findings provide evidence that polymorphisms of DNA repair genes may affect the risk of bladder cancer and those two SNPs (rs1799794 and rs861530) in XRCC3 gene might exert effects on the development of bladder cancer in a northwest Chinese population in both independent and interaction analyses.