XRCC6 encodes the Ku70 protein, a critical component of the DNA double-strand break (DSB) repair machinery that functions primarily through the non-homologous end joining (NHEJ) pathway 1. The protein forms a heterodimer with XRCC5 (Ku80) to create the Ku complex, which binds to DNA breaks and recruits essential repair factors 1. Beyond DNA repair, XRCC6 demonstrates significant involvement in cancer biology through multiple mechanisms. The protein exhibits tumor-promoting effects in osteosarcoma by regulating cell proliferation through the β-catenin/Wnt signaling pathway 2. In lung adenocarcinoma, Ku70 plays a non-classical role in regulatory T cells (Tregs), where it binds to FOXP3 and supports transcriptional activities that maintain immune-suppressive function, contributing to unfavorable prognosis 3. Genetic polymorphisms in XRCC6 show variable cancer associations across populations. Meta-analyses demonstrate that the C1310G polymorphism increases cancer risk, particularly in Asian populations 45. However, some polymorphisms like rs2267437 may confer protective effects against papillary thyroid cancer 6. In nasopharyngeal carcinoma, specific XRCC6 promoter polymorphisms are associated with increased cancer risk and reduced gene expression 7. These findings highlight XRCC6's dual role in DNA repair and cancer pathogenesis, making it a potential therapeutic target.