Ku80 Gene G-1401T Promoter Polymorphism And Risk Of Gastric Cancer

Ku80 gene G-1401T promoter polymorphism and risk of gastric cancerGastric cancer is one of the most frequent malignancies in many countries, accounting for 8.7% of all cancers and 10.4% of all cancer deaths in the year of 2000. In China, gastric cancer remains the leading cause of cancer-related mortality among men and women. It is estimated that about 39% of gastric cancer cases occur in Chinese population. The environmental factors, diet, tobacco, alcohol and Helicobacter pylori (H. pylori) infection are well-known causes of gastric cancer in China. However, only a fraction of individuals exposed to these factors develop gastric cancer, suggesting that individual susceptibility to gastric cancer should be different. Currently, the genomic etiology of gastric cancer is of great interest but largely unknown.DNA damage drives the formation and development of malignant tumors that ameliorate this damage, and its sequelae can be categorized as either gatekeeper or caretaker tumor suppressors, depending on their mode of action. The Ku80 gene, also known as XRCC5, is an important and specific member of NHEJ. Ku70 and Ku80 form a heterodimer called Ku that is well known for its role in NHEJ pathway. Ku acts as a regulator of transcription by interacting with the recombination signal binding protein Jκand the NF-κB p50 homodimer to up-regulate p50 expression, which may regulate the proliferation of gastric cancer cells. Genetic polymorphisms in Ku80 genes influence DNA repair capacity and change predisposition of several cancers, including colorectal, bladder and oral cancers. In addition, in these hospital-based case-control studies of other cancers, it was reported that the frequency of GT/TT type of the Ku80 gene at promoter G-1401T (rs828907) was significantly higher in cases than in controls. Thus, we assumed that the specific polymorphism of Ku80 gene may also contribute to gastric cancer. To test the hypothesis that the promoter G-1401T polymorphism is associated with the risk of gastric cancer, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) to genotype this polymorphism in a hospital-based case-control study of 241 patients with gastric cancer and 273 age- and sex-matched cancer-free controls. The results of this research will lead to a better understanding of the role of SNPs in the Ku80 genes in gastric cancer carcinogenesis. Such knowledge may eventually lead to the development of better preventive measures for gastric cancer.AIM: To evaluate the possible relationship between the Ku80 gene polymorphism and the risk of gastric cancer in China.METHODS: In this hospital-based case-control study of gastric cancer in Jiangsu Province, China, we investigated the association of the Ku80 G-1401T (rs828907) polymorphism with gastric cancer risk. A total of 241 patients with gastric cancer and 273 age- and sex-matched control subjects were genotyped and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP).RESULTS: The frequencies of genotypes GG, GT and TT were 65.6%, 22.8% and 11.6% in gastric cancer cases, respectively, and 75.8%, 17.6% and 6.6% in controls, respectively. There were significant differences between gastric cancer and control groups in the distribution of their genotypes (P = 0.03) and allelic frequencies (P = 0.002) in the Ku80 promoter G-1401T polymorphism.CONCLUSION: The T allele of Ku80 G-1401T may be associated with the development of gastric cancer.