Association of XRCC1 Polymorphisms and Risk of Differentiated Thyroid Carcinoma: A Case–Control Analysis

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Abstract
Background: Numerous single-nucleotide polymorphisms (SNPs) of the DNA repair gene XRCC1 have been described. These SNPs have been increasingly studied in the epidemiology of various cancer types. In this study we evaluated the risk association between six common SNPs of the XRCC1 gene and differentiated thyroid carcinoma (DTC). Methods: We conducted a case–control study of 251 subjects with DTC, 145 subjects with benign thyroid disease, and 503 cancer-free controls. Polymerase chain reaction–restriction fragment length polymorphism assays were performed for genotyping. Multivariate logistic regression analysis was performed for risk estimation. Expectation-maximization algorithm and bayesian methods were used to estimate haplotype frequencies. Results: Multivariate analysis demonstrated an increased risk of DTC for the Arg194Trp heterozygous polymorphic (CT) genotype (odds ratio [OR]: 1.4, 95% confidence interval [CI]: 0.9–2.1). Multivariate analysis demonstrated a decreased risk of DTC for the Arg399Gln homozygous polymorphic (AA) genotype (OR: 0.5, 95% CI: 0.3–0.8) and the polymorphic (A) allele (OR: 0.7, 95% CI: 0.5–1.0). Compared to the most commonly observed haplotype (CGTCGA), multiple haplotypes were associated with a significantly increased risk of DTC, with the CGTTGG haplotype demonstrating the strongest association (OR: 5.0, 95% CI: 1.9–13.2). Conclusions: The XRCC1 194Trp variant allele may be associated with increased risk of DTC, while the XRCC1 399Gln variant allele may be associated with decreased risk of DTC. The utility of XRCC1 haplotypes in predicting DTC risk deserves further investigation with direct haplotype measurement.