| Gastric cancer(GC) is one of the most common malignant tumors of the digestive system in the world, growing at nearly 800,000 new cases every year, and is the fourth place in the global incidence of malignant tumors, according to World Health Organization(WTO) statistics. About 70 million people died of gastric cancer or gastric cancer associated disease every year, ranking the second most common cancer cause of death.According to geographical location, stomach cancer occurs mainly in Asia, Africa and South America and other developing countries. In Asian countries, for example, China,Japan and South Korea, new gastric cancer cases of each year accounts for two-thirds of global cases. Among them, China as the world’s most populous countries, the annual cases of new-onset of gastric cancer accounts for about 1/2 of the total global gastric cancer,which was more than lung cancer and is the second largest just below lethal malignancy.Although in recent years with the application of improved surgical techniques and chemotherapy and other technical means, the mortality rate of gastric cancer has been decreased, but the five-year survival rate of gastric cancer is still low. A large number reports have confirmed that the gastric cancer is multivariate, multi-stage, multi-gene interaction. A growing number of studies also show that environmental exposure factors and genetic factors played a crucial role on the development and prognosis of gastric cancer and chemotherapy susceptibility. The same individual at different environmental exposures is often only a small number of people suffering from stomach cancer, and the prognosis and sensitivity to chemotherapy also have significantly difference, the results are suggesting that there may be differences in individual susceptibility and prognosis of gastric cancer.As the human genome project, a large number of studies have found that genetic variation will have a major impact on the structural gene expression and molecularregulatory functions, and further lead to changes in the regulation of the biological function.Single nucleotide polymorphisms(single nucleotide polymorphisms, SNPs) are the most common genetic variation. Numerous studies show that genetic variation determines the individual suffering from cancer genetic susceptibility. The SNPs were able to change the structure or expression of the gene, which affects the regulation of genes. Chemotherapy plays an important role in the treatment of gastric cancer, with fluorouracil and platinum being the common drugs. However, patients respond differently to the same drugs, the mechanism of which may be important to be clarified to improve the efficacy of chemotherapy.MiRNAs(microRNAs) are a class of small noncoding RNAs(18-23 nt),which play the roles in numerous processes, including development, proliferation, apoptosis and carcinogenesis. Studies have found that SNP singly or jointly can contribute to carcinogenesis, and possibly have gene-gene and gene-environment interactions. In 2008,Hu and his colleagues had observed that miR-196a2 rs11614914 can influence the process of pre-miRNA to the mature miRNA, and this SNP was associated with lung cancer risk.However, there are few studies to explore the association between miR-196a2 rs11614914 and gastric cancer risk. Recently, many studies have shown that the abnormal expression of miRNAs are related with the development of gastric cancer: if SNP occured in the sequence of pri-miRNA(primaiy miRNA), it may affect the formation of the pre-miRNA(precursor miRNA) and mature miRNA; SNP is present in the miRNA biological processing key gene(DICER and DROSHA),it may influence the expression and function of miRNA biological processing gene,resulting in alted expression of mature miRNA. As we all known, miRNAs can regulate gene expression at the post-transcriptional level through binding the 3’UTR of target gene mRNA. Thus, if SNP located in the sequence of mature mi RNA, it may affect the binding activity of miRNA and target gene. Currently,miRNAs have been extensively studied, however, the biologic function of miR-196a2rs11614914 in gastric carcinogenesis are not fully clear.Part one A functional polymorphism in MIR196a2 is associated withrisk of gastric cancerRecently, MiRNAs play important roles in carcinogenesis. In this study, we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis.Genetic variations in miRNAs have been demonstrated to be capable of altering miRNA expression, consequently affecting many cancer-related biological processes. The MIR196a2 rs11614913(T > C) polymorphism has been reported to be associated with various cancers development and progression. In our study, we aim to explore whether this polymorphism is relevant to the genetic susceptibility of gastric cancer in a Chinese population.We analyzed the correlations of rs11614913 polymorphism with gastric cancer susceptibility in test and validation sets. The test set comprised 749 cases and 900 controls,while the validation set enrolled 940 cases and 1,046 controls. The variant rs11614913 CC genotype was associated with a significantly reduced risk of gastric cancer in both sets[adjusted odds ratio(OR) = 0.78, 95% confidence interval(CI) = 0.62-0.99 for the test set and 0.64, 0.52-0.80 for the validation set] compared with the CT/TT genotypes.Our results suggested that the genetic variation of MIR196a2 may play a role in gastric cancer tumorigenesis. It may be an important biomarker for gastric cancer susceptibility, and has important significance to improve early diagnosis and treatment of gastric cancer.Part two Effect of The MIR196a2 rs11614913(T > C) polymorphis onsurvival of gastric cancer among patients who receiving postoperativeadjuvant chemotherapyIn the first part of this study, we found that miR-196a2 rs11614913 genetic polymorphism was significantly associated with susceptibility to gastric cancer. However,whether there is a link between the survival and chemosensitivity of gastric cancer patients after surgery need to be further large population verification.This retrospective cohort study design, to explore the relationship between miR-196a2rs11614913 and prognosis and chemosensitivity of gastric cancer. This study retrospectively collected Yixing City, Jiangsu Provincial People’s Hospital for treatment and underwent surgery in patients with new-onset cancer, who were diagnosed by histopathology, no sex, age and pathological type of restriction. And a total of 1022 cases were collected. After five years of follow-up, there were 940 cases of samples were included in the study. the CC genotype was associated with a significantly increased survival of gastric cancer compared with the CT/TT genotypes [adjusted hazard ratio(HR)= 0.72, 95% CI = 0.55-0.95], and the association was more prominent among patients with non-cardia gastric cancer than those with cardia gastric cancer(adjusted HR = 0.57, 95%CI = 0.40-0.83 for NCGC and 1.00, 0.65-1.53 for CGC)This study suggested that mi R-196a2 rs11614913 may play key role on prediction prognosis of gastric cancer patients. But relationship between chemosensitivity of gastric cancer should be further verified by a large sample. |
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