Xrcc6-flox Mouse

XRCC6, also known as Ku70, is a gene encoding a protein that plays a crucial role in the DNA non-homologous end-joining (NHEJ) pathway, which is the main mechanism for repairing DNA double-strand breaks (DSBs) in human cells. Maintaining genomic stability by repairing DSBs is essential in preventing tumor initiation and progression, thus XRCC6 is of great biological importance in carcinogenesis [2].

Multiple studies have investigated the association between XRCC6 polymorphisms and cancer risks. A meta-analysis showed that the rs2267437 polymorphism was associated with an increased risk of overall cancers, breast cancer, renal cell carcinoma, and hepatocellular carcinoma, especially in Asian populations [1]. Another study on nasopharyngeal carcinoma (NPC) found that the TC and CC genotypes of the XRCC6 promoter T-991C polymorphism were associated with a significantly increased NPC risk, and lower XRCC6 mRNA and protein expression was observed in NPC samples with these genotypes [3]. In a Taiwanese population, similar results were found for hepatocellular carcinoma (HCC), where the TC and CC genotypes of the XRCC6 promoter T-991C polymorphism increased the HCC risk, along with lower XRCC6 mRNA and protein expressions [4]. In esophageal squamous cell carcinoma (ESCC), the CG carriers and G allele carriers of rs2267437 were at a higher risk of ESCC [5]. In contrast, in the Polish population, the XRCC6 C1310G polymorphism was associated with a decreased risk of colorectal cancer [6]. Additionally, high expression of XRCC6 promoted human osteosarcoma cell proliferation through the β-catenin/Wnt signaling pathway [7].

In conclusion, XRCC6 is crucial for DNA double-strand break repair through the NHEJ pathway, which is significant in maintaining genomic stability and preventing carcinogenesis. Studies on XRCC6 polymorphisms have revealed its associations with various cancers, such as breast, renal cell, hepatocellular, nasopharyngeal, esophageal squamous cell, and colorectal cancers, as well as osteosarcoma, providing insights into the role of XRCC6 in different disease conditions.