Dataset Information

AB160. Association of nineteen polymorphisms from seven DNA repair genes and the risk for bladder cancer in China

ABSTRACT:

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 cross-validation 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.

SUBMITTER: Zhu G

PROVIDER: S-EPMC4842511 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND AND OBJECTIVE: The X-ray repair cross-complementing group 1 (XRCC1) protein plays a crucial role in base excision repair (BER) pathway by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, a comprehensive meta-analysis of all available studies was performed in this study. METHODS: PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases have been systematically searched to identify all relevant studies for the period up to February 2013. Data were abstracted independently by two reviewers and Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed mainly by ethnicity and smoking status. RESULTS: A total of 26 case-control studies, including 24 studies for R399Q polymorphism, 15 studies for R194W polymorphism, and 7 studies for R280H polymorphism met the inclusion criteria and were selected. With respect to R399Q polymorphism, significantly decreased bladder cancer risk was found among smokers (AA vs. GG: OR=0.693, 95%CI= 0.515-0.932, P=0.015 and recessive model AA vs. GA+GG: OR=0.680, 95%CI= 0.515-0.898, P=0.007, respectively). With respect to R194W and R280H polymorphism, significantly increased bladder cancer risk were observed among Asians (TT+CT vs. CC:OR = 1.327, 95% CI 1.086-1.622, P=0.006 for R194W, and AA+GA vs. GG: OR=2.094, 95% CI 1.211-3.621, P=0.008 for R280H, respectively). CONCLUSIONS: This meta-analysis suggests that the XRCC1 R399Q polymorphism may play a protective role against bladder cancer among smokers. However, the XRCC1 R194W and R280H polymorphisms were both associated with increased bladder cancer risk among Asians. Further studies with larger sample sizes are needed to validate our finds.