Relationships Between DNMT1 And Non-cardiac Gastric Cancer

Objective To investigate the roles of SNP rs2228611,rs16999593 in the DNMT1gene in Helicobacter pylori(H.pylori)infection and non-cardia gastric cancer risk by case-control association study.And to supply the theoretical basis and experimental data for the early diagnosis and treatment of non-cardiac gastric cancer.Methods In the present study,381 cases with non-cardia gastric cancer and 427 normal controls were recruited in Baotou Han population.All subjects were unrelated and had been in Baotou for more than 5 years.H.pylori infection was detected by Enzyme-linked immunosorbent assay(ELISA)in 427 normal controls.The protein expression level of DNMT1 was detected in 126 non-cardia gastric cancer tissues and 104 normal gastric mocosa tissues by immunohistochemical method.SNP rs2228611,rs16999593 were genotyped by Taq Man method in all subjects.And data was analyzed by unconditional logistic regression to evaluate the association of SNP rs2228611 and rs16999593 with H.pylori infection and non-cardia gastric cancer risk as well as protein expression level of DNMT1.Results(1)The rates of H.pylori infection in controls were 47.31%.(2)The positive expression rates in non-cardia gastric cancer tissues and normal controls were84.13%and 53.85%,respectively.The expression level of DNMT1 in non-cardia gastric cancer tissues was significantly higher than in the controls(χ~2=25.087,P=0.000).The expression of DNMT1 was related to the degree of differentiation of gastric cancer,lymph node metastasis(P<0.05).(3)SNP rs16999593 was associated with non-cardia gastric cancer risk in overdominant model.Compared with TT+CC genotype carriers,the risk of non-cardia gastric cancer was reduced in CT carriers(OR=0.70,95%CI=0.51-0.96).(4)SNP rs16999593 was not associated with H.pylori infection.(5)SNP rs2228611 were not associated with H.pylori infection and non-cardia gastric cancer risk in codominant,dominant,recessive,overdominant,and log-additive models.(6)SNP rs2228611 and rs16999593 were not associated with the protein expression levels of DNMT1.Conclusions(1)The expression level of DNMT1 in non-cardia gastric cancer tissues is significantly higher than in the controls.(2)SNP rs2228611 and rs16999593 are not associated with H.pylori infection.(3)SNP rs16999593 is associated with non-cardia gastric cancer risk in overdominant model,the risk of non-cardiac gastric cancer is reduced in CT carriers,The CT genotype of SNP rs16999593 may be the protective factor for non-cardiac gastric cancer in Baotou Han population.(4)SNP rs2228611 is not associated with non-cardia gastric cancer risk.(5)SNP rs2228611 and rs16999593 are not associated with the protein expression level of DNMT1.