| As the most common malignant cancer in the world, gastric cancer threatens people health seriously. In China, more than260000died of gastric cancer each year. In addition, new cases of gastric cancer in our country roughly accounts for40%among world. With the development of endoscopy, endoscopic ultrasound and spiral CT technology, it’s useful for gastric cancer prevention and early diagnostic. Overall, however, early diagnosis and recovery rate of gastric cancer is still relatively low. Etiology of gastric cancer is complex. Many studies revealed that the mechanism that contributing to the development of gastric cancer was a multi-factor, multi-stage, multi-step and multi-gene changing process. Risk factors of gastric cancer can be classified in exogenous and endogenous. Exogenous factors include H. pylori infection, smoking, the high-salt diet and career-related factors. Endogenous factors include de body’s genetic background, immune status, and hormone levels. With the development of tumor immunology, more and more scientists have believed that immune system was associated with the development of cancer. Many studies showed that the immune system had immune surveillance and immune responses to tumors. On the other side, tumors can escape immune system surveillance and further lead to tumor growth. To date, although the function of inhibitory molecules and immunosuppressive subgroup cells in tumor growth have been accepted and the mechanisms of tumor immunity and immune escaping have made some progress, the mechanisms of tumor immunity and immune escaping are still unclear. It is very important to found tumor antigen for diagnostic and therapeutic, especially the regulatory immune molecules and immune cells in the tumor immune escape. As an important part of humoral immunity, complement system plays an important role in tumor immunity, such as immune regulation, direct killing and chemotaxis. CFH, which can induce the activation of alternative pathway of complement system by binding to C3b and further destroying C3convertase, is an inhibiter of alternative pathway. The abnormal expression of CFH has been found in many tumors. The inhibition function of CFH can protect tumor cells from membrane attack complex (MAC) attacking. Some tumor cells can secrete antoanti-CFH antibody to reduce the suppression of complement。Currently, studies have found that CFH gene polymorphism associated with the risk of non-small cell lung cancer.Objective:Our study aimed to evaluate the association between single nucleotide polymorphisms (SNPs) at CFH genes and gastric cancer risk. In order to provides an important molecular basis for early detection and early diagnosis of gastric cancer.Methods:A case-control study including500patients included histopathologically confirmed gastric cancer and500controls were randomly selected from a pool of a cancer-free population from a nutritional survey conducted in the same region during the same period. The phenol/chloroform extraction and ethanol precipitation was used to isolate genomic DNA from the peripheral blood lymphocytes obtained from2ml whole blood sample of all controls and gastric cancer patients. Based on the Chinese population data from HapMap database, candidate tag SNPs were selected. Genotyping was performed using iPlex Gold Genotyping Asssy and Sequenom MassArray (Sequenom, San Diego, CA, USA). Sequenom’s MassArray Designer was used to design PCR and extension primers for each SNP. Chi-square test was used to compare the distribution of gender, age and smoking status. Multivariate logistic regression was used to estimate OR and95%CI the association of CFH variants and the risk of gastric cancer. Gene-gene and gene-smoking interactions were analyzed by open-resource GMDR software package and Quanto.Results:Total17selected tag SNPs of CFH in HapMap database among Chinese population were analyzed, including rs1065489, rs12144939, rsl831281, rs4658046, rs6695321, rs7524776, rs1061170, rs10733086, rs1329428, rs3753394, rs3766404, rs800292, rs10922096, rsl1582939, rs2019727, rs505102, rs6680396.Result showed CFH rs1061170(402Try/His) polymorphism was related to the risk of gastric cancer.CFH rs1061170have402Try/Try、402Try/His and402His/His three genotypes, and the three genotype frequencies in the cases and controls respectively was82.4%,15.2%,2.4%and87.4%,12.4%,0.2%.Further multivariate regression analysis showed that the rs1061170402His allele carriers increase the risk of gastric cancer compared with the402Try/Try carriers with OR (95%CI),1.47(1.03-2.08), P=0.034.402His/His genotype carriers have more chance to increase the risk of gastric cancer, compared with the402Try/Try carriers with OR (95%CI),12.41(1.60-96.34).While, we didn’t find any significant difference in genotype frequencies between gastric cancer patients and controls for any other SNPs tested. There was no interaction among the CFH tag SNP in susceptibility to gastric cancer. We also did not found interaction between the risk of gastric cancer in gender, age and CFHrs1061170polymorphism. When stratified by smoking status, the risk of gastric cancer was associated with the402His allele carriers in non-smokers with OR (95%CI) of1.92(1.21-3.06),and in smokers OR (95%CI) of1.15(0.67-1.99),1.14(0.83-1.55). There was no interaction between the genotype of CFH402Try/His and smoking in susceptibility to gastric cancer. Conclusion:1. Complement factor H Try402His polymorphism effects on the susceptibility to gastric cancer in Chinese population.2. There was no interaction among the CFH tag SNPs in susceptibility to gastric cancer.3. There was no interaction between the genotype of CFH402Try/His and gender, age and smoking in susceptibility to gastric cancer. |
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