Association between Polymorphisms of X-ray Repair Cross Complementing ۵ and ۶ Promoter Genes and the Risk of Metastatic Breast Cancer

Background and Objective: Breast cancer is the second leading cause of cancer-related death in women. Better individualized treatment needs novel prognostic predictors. X-ray repair cross complementing XRCC۵ and XRCC۶ are coding genes of the Ku protein complex (key components of the non-homologous end-joining [NHEJ] pathway), which could serve as prognostic factors in breast cancer. Hence, in this study, the association of XRCC۵ (coding the Ku۷۰ subunit) and XRCC۶ (coding the Ku۸۰ subunit) single polymorphisms with the risk of metastatic breast cancer was assessed. Materials and Methods: This study included ۳۰ breast cancer patients and ۳۰ age-matched healthy women. Tetra-Arms polymerase chain reaction (PCR) and high-resolution melt (HRM) real-time PCR were performed to determine XRCC۵ (variable number tandem repeat [VNTR] polymorphism, rs۶۱۴۷۱۷۲) and XRCC۶ (rs۱۳۲۷۹۳) polymorphisms, respectively. Demographical and clinical tumor status was recorded for all women. Allele frequencies and related genotypes were identified. Results: Our results indicated that ۳۴% of patients receiving chemotherapy had metastases in other organs, mostly in the lung. The frequencies of ۰R/۰R, ۱R/۱R, ۲R/۲R, and ۱R/R genotypes in the XRCC۵ gene were ۶.۶%, ۶۳.۳%, ۶.۶%, and ۲۳.۳%, respectively. No significant association was found between XRCC۵ and metastatic breast cancer (P = ۰.۴۲۶). In addition, the XRCC۵ polymorphism was associated with progesterone (P = ۰.۰۶۸), as well as the time interval between chemotherapy and relapse (P = ۰.۰۶۹). The frequency of AA, GG, and AG genotypes in XRCC۶ were ۰%, ۳۳.۳%, and ۶۶.۷%, respectively. The XRCC۶ polymorphism was associated with cancer metastasis. There was a significant relationship between age (P = ۰.۰۴۸) and family history (P = ۰.۰۲۰) with cancer incidence. A significant association was observed between the XRCC۶ polymorphism with human epithelial receptor ۲ (HER۲; P = ۰.۰۷۰) and radiotherapy sessions (P = ۰.۰۰۷). Conclusion: We speculate that the genetic variation of the XRCC۶ gene (rs۱۳۲۷۹۳ SNP) might be considered as a diagnostic biomarker in breast cancer, but further studies are necessary to confirm the results.