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XRCC1 Polymorphisms and Cancer Risk: A Meta-analysis of 38 Case-Control Studies

¹ Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, Nanjing, China and ² Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Hongbing Shen, Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, 140 Hanzhong Road, 210029 Nanjing, China. Phone: 86-25-868-62747; Fax: 86-25-865-27613. E-mail: hbshen{at}njmu.edu.cn

Several potential functional polymorphisms (Arg¹⁹⁴Trp, Arg²⁸⁰His, Arg³⁹⁹Gln) in the DNA base excision repair gene X-ray repair cross-complementing group 1 (XRCC1) have been implicated in cancer risk. Our meta-analysis on total of 11,957 cancer cases and 14,174 control subjects from 38 published case-control studies showed that the odds ratio (OR) for the variant genotypes (Trp/Trp + Arg/Trp) of the Arg¹⁹⁴Trp polymorphism, compared with the wild-type homozygote (Arg/Arg), was 0.89 [95% confidence interval (95% CI), 0.81-0.98] for all tumor types without between-study heterogeneity. Similarly, the overall risk for the combined variant genotypes (His/His + Arg/His) of the Arg²⁸⁰His, compared with the wild homozygote (Arg/Arg), was 1.19 (95% CI, 1.00-1.42). However, there was no main effect in either recessive or dominant modeling for the Arg³⁹⁹Gln, and the variant Gln/Gln homozygote was not associated with overall cancer risk (OR, 1.01; 95% CI, 0.90-1.14). The analyses suggest that XRCC1 Arg¹⁹⁴Trp, Arg²⁸⁰His polymorphisms may be biomarkers of cancer susceptibility and a single larger study with thousands of subjects and tissue-specific biochemical and biological characterization is warranted to further evaluate potential gene-to-gene and gene-to-environment interactions on XRCC1 polymorphisms and cancer risk.

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