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Int J Med Sci 2012; 9(6):498-505. doi:10.7150/ijms.4799

Research Paper

Interaction between Polymorphisms of DNA Repair Genes Significantly Modulated Bladder Cancer Risk

Yi Zhi1,2*, Jing Yu1*, Yang Liu3, Quanfang Wei1, Fang Yuan2, Xiaozhou Zhou2, Bo Song2, Zhiwen Chen2, Jin Yang1,✉

1. Department of Cell Biology, Third Military Medical University, Chongqing 400038, China;
2. Urology Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China;
3. Department of Urology, The 452nd Hospital of PLA, Chengdu 610021, China.
* Equal study contribution.

Abstract

DNA repair is a primary defense mechanism against damage caused by exogenous and endogenous sources. We examined the associations between bladder cancer and 7 polymorphisms from 5 genes involved in the maintenance of genetic stability (MMR: MLH1-93G>A; BER: XRCC1--77T>C and Arg399Gln; NER:XPC Lys939Gln and PAT +/-; DSBR:ATM G5557A and XRCC7 G6721T) in 302 incident bladder cancer cases and 311 hospital controls. Genotyping was done using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The homozygous variant of XRCC7 G6721T (Odds Ratio [OR]: 2.36; 95% Confidence Interval [CI]: 1.13-4.92) was associated with increased bladder cancer risk. In an analysis of combined genotypes, the combination of XRCC1Arg399Gln (Gln allele) with XRCC1-77 T/T led to an increase in risk (OR: 1.61; 95% CI: 1.10-2.36). Moreover, when the XPCLys939Gln (Gln allele) (nucleotide excision repair [NER]) was present together with XRCC7 (T allele) (double strand break repair [DSBR]), the bladder cancer risk dramatically increased (OR: 4.42; 95% CI: 1.23-15.87). Our results suggest that there are multigenic variations in the DNA repair pathway involved in bladder cancer susceptibility, despite the existence of ethnic group differences.

Keywords: Polymorphism, DNA repair, Ataxia telangiectasia mutated, MutL homolog 1, Transitional cell carcinoma, Multigenic variations.

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How to cite this article:
Zhi Y, Yu J, Liu Y, Wei Q, Yuan F, Zhou X, Song B, Chen Z, Yang J. Interaction between Polymorphisms of DNA Repair Genes Significantly Modulated Bladder Cancer Risk. Int J Med Sci 2012; 9(6):498-505. doi:10.7150/ijms.4799. Available from http://www.medsci.org/v09p0498.htm