| Gastric cancer is the most common malignant tumor of the digestive system,whose incidence and the mortality rate ranking the fourth and the second in the wordrespectively, has become a threatening disease to human health. East Asia and SouthAmerica countries are the high risk areas of gastric cancer. In China, gastric cancer isthe most frequency of the various tumors, and accounts for nearly25%leading causeof cancer-related death. It occures at any age especially at55-70ages, men are twotimes more susceptible to gastric cancer than women.Gastric cancer is a multifactor disorder that is thought to result from an interactionbetween genetic background and environmental factors, but the precise mechanism isnot elucidated at present. Previous studies have indicated that dietary factors，helicobacter pylori (Hp)，precancerous lesions and familial transmissibility are riskfactors for gastric cancer. The present situation on the prevention and cure of gastriccancer in our country are less than satisfactory. For example, incidence and mortalityrate are still higher. Meanwhile, early diagnosis rate, radical resection rate andsurvival rate of5-years are lower.Rensently, studies pay more and more attention on single nucleotidepolymorphisms(SNPs), which play an important role in the susceptibility andprognosis to gastric cancer and become the hot point of researching. Geneticpolymorphism makes different individuals who exposed to the same environment orin the same TNM period have different risks and outcomes of cancer. The geneticsusceptibility of gastric cancer is showed to be related to low codominant genemutation. The genome-wide association study (GWAS) can select SNP associatedwith diseases through identifying the presence of sequence variation within thehuman genome.The current researches have focused on exploration of prognosis biomakers in tumor gene level. Some studies demonstrated that variations of gene involved incarcinogenesis, development and prognosis of cancers, including breast cancer,gastric cancer and so on. TOX3rs3803662and2q35rs13387042are identified to beassociated with breast cancer by GWAS. Therefore, the aim of this study was toinvestigate whether SNP rs3803662and SNP rs13387042are associated withprognosis of gastric carcinoma in Chinese patients. Teasting for the presents of thesepolymorphisms maybe find new molecular markers predicting the prognosis ofgastric cancer. Moreover, it can offer a very promising prospect for exploring andtranslating our findings into further potential clinical and diagnostic therapeuticapplications in gastric cancer. Part I. A genetic polymorphism in TOX3is associated withsurvival of gastric cancer in a Chinese populationPurpose: Recently, genetic polymorphism (rs3803662C>T) in TOX3was reported tobe associated with susceptibility and prognosis of breast cancer. In this study, wehypothesized that rs3803662could influence gastric cancer survival outcomes.Methods: With multiplex SNaPshot method, we genotyped TOX3rs3803662in880gastric patients with surgical resection. The association between genotype andsurvival outcomes was performed by the Kaplan-Meier method. The crude hazardratios (HRs), their95%confidence intervals (CIs) and adjusted HRs were estimatedby Cox regression analysis. Cox stepwise regression analysis was also performed todetermine prognostic factor in gastric cancer. Three genetic models (codominant,dominant and recessive) were used to assess the association of TOX3rs3803662withsurvival outcome of gastric cancer patients. All P values in this study were2-sided. P<0.05was considered statistically significance. All the statistical analyses wereperformed with SPSS13.0software.Results: There was no association in the analyses of rs3803662and survival ofgastric cancer. However, the stratified analysis by histology showed that rs3803662CT/TT genotype was associated with a significantly better survival for diffuse-typegastric cancer (log-rank P=0.030, hazard ratio (HR)=0.67,95%confidence interval(CI)=0.46–0.96), than the CC genotype. In addition, this favorable effect wasespecially obvious among gastric cancer patients with tumor size>5cm, T3and T4depth of invasion, lymph node metastasis and no distant metastasis.Conclusions: TOX3rs3803662might play an important role in the prognosticoutcome of diffuse-type gastric cancer, especially perhaps further help in explainingthe reduced risk of death associated with diffuse-type gastric cancer. Part II. The associations between2q35rs13387042polymorphism and survival of gastric cancer in a ChinesepopulationPurpose: Several GWAS have reported the relationship between the geneticpolymorphism of2q35rs13387042and breast cancer. We evaluated the impactof SNP rs13387042on the prognosis of gastric cancer.Methods:915Chinese patients with resectable gastric cancer were genotypedfor2q35rs13387042using multiplex SNaPshot method. Genotyping and calculatingmethods are same with Part I.Results: No statistically significant difference were found between rs13387042andthe survival of gastric cancer. Then, patients above60years old are regarded as studyobjects. In the stratified analysis of elderly patients with gastric cancer by tumor size，a25%risk of death in patients carrying the GA/AA genotype was relatively reduced(HR=0.75,95%CI=0.47–1.21) than the GG genotype among patients with tumorsize≤5cm. In addition, a protective effect was significant among patients with nodistant metastasis (HR=0.68,95%CI=0.41–0.93) and intestinal-type gastric cancer(HR=0.61,95%CI=0.33–0.97).Conclusions:2q35rs13387042is not associated with the prognosis of gastric cancerin Chinese patients. More studies were needed to confirm our results. |
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