Abstract
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 potential effect 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 patients and 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 by PCR-RFLP and PCR-HRM analysis was carried out to evaluate XRCC2 (R188H) . Separately, Rad51, Rad52 and XRCC2 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 for patients 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 revealed an elevated risk of DTC (p value: 0.007). It is recommended that Rad52 2259C>T, XRCC2 R188H and XRCC3 T241M polymorphisms should be simultaneously considered as contributing to a polygenic risk of differentiated thyroid carcinoma.
Highlights
Most cancers are initiated by DNA damage accumulation (Lengauer et al, 1998)
The role of Rad51 135G>C, Rad52 2259C>T, XRCC2 R188H and XRCC3 T241M polymorphisms in different cancers were assessed in several case-control studies
In this study we evaluated the association of afore-mentioned polymorphisms separately, and for the first time, assessment of combined genotypes with each other, on individual susceptibility in Iranian differentiated thyroid carcinoma (DTC) patients
Summary
Most cancers are initiated by DNA damage accumulation (Lengauer et al, 1998). Several forms of DNA damage such as double strand breaks (DSBs) must be repaired for cells to survive (Tambini et al, 2010). To evaluate the potential effect 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 patients and cancer-free controls. Rad51, Rad52 and XRCC2 polymorphisms were not shown to be more significant in patients when compared to controls in crude, sex-adjusted and age-adjusted form.
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