Association between Polymorphisms of X-ray Repair Cross Complementing 5 and 6 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 XRCC5 and XRCC6 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 XRCC5 (coding the Ku70 subunit) and XRCC6 (coding the Ku80 subunit) single polymorphisms with the risk of metastatic breast cancer was assessed. Materials and Methods: This study included 30 breast cancer patients and 30 age-matched healthy women. Tetra-Arms polymerase chain reaction (PCR) and high-resolution melt (HRM) real-time PCR were performed to determine XRCC5 (variable number tandem repeat [VNTR] polymorphism, rs6147172) and XRCC6 (rs132793) polymorphisms, respectively. Demographical and clinical tumor status was recorded for all women. Allele frequencies and related genotypes were identified. Results: Our results indicated that 34% of patients receiving chemotherapy had metastases in other organs, mostly in the lung. The frequencies of 0R/0R, 1R/1R, 2R/2R, and 1R/R genotypes in the XRCC5 gene were 6.6%, 63.3%, 6.6%, and 23.3%, respectively. No significant association was found between XRCC5 and metastatic breast cancer (P = 0.426). In addition, the XRCC5 polymorphism was associated with progesterone (P = 0.068), as well as the time interval between chemotherapy and relapse (P = 0.069). The frequency of AA, GG, and AG genotypes in XRCC6 were 0%, 33.3%, and 66.7%, respectively. The XRCC6 polymorphism was associated with cancer metastasis. There was a significant relationship between age (P = 0.048) and family history (P = 0.020) with cancer incidence. A significant association was observed between the XRCC6 polymorphism with human epithelial receptor 2 (HER2; P = 0.070) and radiotherapy sessions (P = 0.007). Conclusion: We speculate that the genetic variation of the XRCC6 gene (rs132793 SNP) might be considered as a diagnostic biomarker in breast cancer, but further studies are necessary to confirm the results.

Association between Polymorphisms of X-ray Repair Cross Complementing 5 and 6 Promoter Genes and the Risk of Metastatic Breast Cancer Keywords:

Breast cancer , Metastasis , Polymorphism , XRCC5 , XRCC6