Radiation Response Genotype and Risk of Differentiated Thyroid Cancer: A Case-Control Analysis

Background: Radiation is the only clear etiologic agent for differentiated thyroid cancer (DTC). Understanding the factors affecting sensitivity to gamma radiation and susceptibility to DTC will be critical to early detection and prevention of DTC. Hypothesis: Germline variants of double-strand break repair genes are markers of DTC risk. Objective: Determine the frequency of common single nucleotide polymorphisms of genes of the double-strand break repair pathway in patients with DTC and cancer-free controls. Study Design: Case-control study. Methods: This study included 134 patients with DTC, 79 patients with benign thyroid lesions, and 166 cancer-free control subjects. To avoid ethnic confounding, all subjects were non-Hispanic whites. Genotype analyses were performed on DNA isolated from peripheral blood lymphocytes. Multivariate logistic regression analyses were performed to estimate the risk of DTC associated with each variant genotype. Results: The XRCC3 18067T polymorphic allele was found significantly more commonly among the DTC cases than for the control subjects (P = .006). After multivariate adjustment, having the XRCC3 18067T allele was associated with an increased risk of DTC (adjusted odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3 to 3.4; P = .004). In addition, there was a suggestion that the XRCC3 18067T polymorphic allele was more common among the patients with benign thyroid disease (P = .054), and the homozygous polymorphic genotype was associated with risk for benign thyroid disease (adjusted OR = 2.1; 95% CI = 0.9–4.9; P = .078). Conclusions: In this case-control analysis, the XRCC3 18067T polymorphism is associated with DTC risk. However, such work needs confirmation in larger studies.