Increased Risk of Differentiated Thyroid Carcinoma with Combined Effects of Homologous Recombination Repair Gene Polymorphisms in an Iranian Population

Homologous recombination (HR) repair has a crucial role to play in the prevention of chromosomal instability,and it is clear that defects in some HR repair genes are associated with many cancers. To evaluate the potentialeffect of some HR repair gene polymorphisms with differentiated thyroid carcinoma (DTC), we assessed Rad51(135G>C), Rad52 (2259C>T), XRCC2 (R188H) and XRCC3 (T241M) polymorphisms in Iranian DTC patientsand cancer-free controls. In addition, haplotype analysis and gene combination assessment were carried out.Genotyping of Rad51 (135G>C), Rad52 (2259C>T) and XRCC3 (T241M) polymorphisms was determined byPCR-RFLP and PCR-HRM analysis was carried out to evaluate XRCC2 (R188H) . Separately, Rad51, Rad52 andXRCC2 polymorphisms were not shown to be more significant in patients when compared to controls in crude,sex-adjusted and age-adjusted form. However, results indicated a significant difference in XRCC3 genotypes forpatients when compared to controls (p value: 0.035). The GCTG haplotype demonstrated a significant difference(p value: 0.047). When compared to the wild type, the combined variant form of Rad52/XRCC2/XRCC3 revealedan elevated risk of DTC (p value: 0.007). It is recommended that Rad52 2259C>T, XRCC2 R188H and XRCC3T241M polymorphisms should be simultaneously considered as contributing to a polygenic risk of differentiatedthyroid carcinoma.