Abstract
To evaluate contribution of single nucleotide polymorphisms (SNPs) of X-ray repair cross-complementing group 1 (XRCC1) gene to the risk of cervical carcinoma, we conducted a case-control study of 1012 patients including 539 carcinoma and 473 cervical intraepithelial neoplasia (CIN) and 800 normal women controls and genotyped three XRCC1 SNPs (Arg194Trp, Arg280His, and Arg399Gln). We found that compared with the Arg399Gln (GG), subjects carrying the homozygous Gln399Gln (AA) genotype had a significantly 2.32-fold increased risk of cervical carcinoma (95% CI 1.47-3.65), heterozygous Arg399Gln (GA) genotype were also associated with a significantly increased risk of cervical carcinoma, with the adjusted odds ratio (OR) being 1.58 (95% CI 1.24-2.00). Similarly, compared with Arg194Arg (CC) wild-type genotype, elevated risks were associated with the Trp194Trp (TT) for carcinoma (ORs and 95% CIs being 2.09 [1.45-3.02]) but not for heterozygote Arg194Trp (CT). In addition, three common haplotypes were found to be associated with an increased risk of cervical carcinoma. Using 194Arg-280Arg-399Arg as the reference, the OR and 95% confidence interval for 194Arg-280Arg-399Gln, 194Arg-280His-399Arg, 194Trp-280Arg-399Arg were 2.30 (1.86-2.85), 1.85 (1.41-2.41), 1.98 (1.62-2.40), respectively. The significantly increased risk associated with the haplotypes was also observed in squamous cell carcinoma (SCC) for all three common haplotypes using 194Arg-280Arg-399Arg as the reference. Neither difference was found for adenocarcinoma and CIN. All three SNPs and haplotypes did not confer more risk of high-risk human papillomavirus infection in carcinoma, CIN, and normal subgroup. Our findings suggest that XRCC1 polymorphisms including genotypes and haplotypes contribute to susceptibility to the development of cervical SCC, and the increased susceptibility is probably not through increasing susceptibility to human papillomavirus infection.
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