| Background and aimsGastric cancer is one of the most common neoplasmas worldwide,and mortality from gastric cancer is the second highest in death from malignancies,following to lung cancer,and is the third most common cancer in China.Most of scholars have the consensus that the carcinogenesis of gastric cancer is due to the synergetic effect of Helicobacter pylori(H.pylori) infection,genetic factors,environmental factors,dietetic factors,socioeconomic status,etc.H. pylori infection,which is prevalent in many developing countries such as China with infection rates being over 60%,is an established risk factor in triggering chronic inflammation of the stomach and leading to stepwise development of the malignancy.Yet,for so many carriers, various individuals who were infected with H.pylori could have variable clinical outcomes. Among them only＜3%of individuals ever developed gastric cancer,which indicates that other factors are involved in gastric neoplasias occurrence.Recently,emerging evidences strongly suggest that gastric cancer is associated with polymorphisms of several genes involved in the inflammation pathway.Studies of familial clustering,ethnic differences and polymorphisms of inflammation-related genes have provided evidence that host genetic factors play a pivotal role in the pathogenesis of gastric cancer.The polymorphisms of macrophage migration inhibitory factor(MIF) and tumor necrosis factor(TNF)-αhave association with susceptibility of many diseases,such as coronary heart disease,occupational strain,rheumatoid diseases,but it is seldom reported about the association with gastric cancer. It is rarely seen about the family aggregation of gastric cancer and the change of gastric cancer susceptibility along with the relativeship decreasing through ancestry study.The association research about MIF,TNF-A and the genetic susceptibility of gastric cancer is helpful for us to discover the mechanism of gastric cancer in high prevalence of Henan province,it can make a exact molecular diagnose,screen on the groups with high risks, further provide prognostic analysis possibly.By the case-control familial comparative study,this topic researched on the distribution of polymorphisms of pro-inflammatory cytokines gene MIF and TNF-A in the case's family groups and control's,and the interactive effect between them and H.pylori infection;and ascertained their genetic effect in gastric neoplasia,then probed into and confirmed the association between inflammatory cytokines and the susceptibility of gastric cancer.MethodsTraditional case-control study of epidemiology was combined with familial comparative study in this study.We sampled four villages by cluster sampling from two counties,Xinxiang County and Xin'an County,which have high prevalence of gastric cancer in Henan province, and then interviewed every inhabitant for the occurrence of gastric cancer in their families. We obtained 296 members from cases' families and 319 from controls' families,collected and stored their venous blood samples in -80℃for use.Genome DNA was extracted from the venous blood of all subjects;the polymorphisms genotype were detected by using the polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP) and the polymerase chain reaction(PCR),then the products of MIF and TNF-A were electrophoresed on 2.0%agarose gels or 8.0%polyacrylamide gel.We checked deviation from Hardy-Weinberg equilibrium among cases by aχ~2-test;The H.pylori infection through ELISA was examined;Linkage Disequilibrium Analyzer(LDA) was used for measures of pairwise linkage disequilibrium between SNPs within TNF-A;The interaction about H.pylori infection and polymorphisms of MIF at positions-173 and TNF-A at -238 locus were tested by likelihood ratio test. Results1.In this study,MIF-173C/C genotype was associated with increased risk of non-cardiac adenocarcinoma of stomach[the odds ratio(OR)=2.59,95%confidence interval(95%CI): 1.27～5.26].In the first degree relatives,comparing the cases family with controls family members,the OR values of MIF-173C/C was 8.20(95%CI:2.43～28.68);the association strength reduced along with the relative degree decreasing.2.No difference was found in the frequency distribution of TNF-A-238 genotype between the case and control families.The combination analysis of TNF-A-308 and TNF-A-238 genotypes suggested that combined genotypes of GA/GG,AA/GG and AA/GA had the OR values of 2.07(1.34～3.21),4.49(2.74～7.33),4.98(1.76～14.01).3.The positive H.pylori status could increase the risk of gastric cancer and the risk reduced along with the relative degree decreasing,the OR value was 1.96(95%CI:1.26～3.01) in the first degree and 0.94(95%CI:0.49～1.81) in the second degree.4.The analysis about the two polymorphisms and H.pylori infection suggested that the polymorphism of TNF-A-238 and the H.pylori had interaction to the risk of gastric cancer.Conclusions1.The variant genotype of MIF-173C/C is the risk of gastric cancer,the association strength reduced along with the relative degree decreasing.2.The combined genotypes of GA/GG,AA/GG and AA/GA could increase the risk of gastric cancer comparing with the separate genotypes.3.The infection of H.pylori affected by genetic factor and familiar transmission is a risk factor to gastric cancer;the association strength reduced along with the relative degree decreasing.4.The polymorphism of TNF-A-238 and the H.pylori had interaction to the risk of gastric cancer. |
PDF Full Text Request