Association Between MUC1 A/G SNP At 568 Site And The Risk Of Gastric Cancer

BackgroundAs any other tumors,it was the interaction of the gene-environment which attributed to the incidence of gastric cancer.Experimental animal genetics and pharmacological studies show that individual exogenous and endogenous metabolism of carcinogens difference can be as much as several times and even hundreds of times.Individual differences in genetic susceptibility gene polymorphism are the basis.It is these gene polymorphisms influence or "modified" different individuals on the role of environmental factors sensitivity.The gastric mucus of normal human beings were secreted by the surface of epithelial cells,cardiac gland,pyloric glands and acid secretion glandular of mucous cervical cells,and mucin MUC1 was a very important component of the mucus,and it constituted a "mucus--bicarbonate barrier" with HCO3~- together,which can protect the gastric mucosa.MUC1 protein was encoded by the gene of its same name.MUC1 gene was located in the 1q21-24,and it was known that the second exon exist the variable number tandem repeats(VNTR)polymorphism and a A/G single nucleotide polymorphism(SNP)at 568 site on its upstream.It was reported by Ligtenberg that two polymorphic loci caused a 27 bp difference after mRNA modified,which further formed the difference of nine amino acids in the protein translation.So SNP led to the length and the structure variation of MUC1.In the study about the A/G polymorphism at 568 site and diseases,Janssen found it had relationship with the expression KL-6 in the serum,which was MUC1 antibody in the lungs and a pulmonary fibrosis indicator,thus, whether there was relationship the SNP which was a structural change in MUC1 gene and susceptibility to gastric cancer in the local population? Whether it could lead to the variation of the structure and function of the protein encoded by it? It has not been reported until now.We analyzed the distribution of MUC1 A/G polymorphism at 568 site on Liaoning population in China on this study,and approach the relationship between the A/G polymorphism and susceptibility to gastric cancer;as well as the effect of the A/G polymorphism on MUC1 protein expression.We aimed at finding a potential risk factor of gastric cancer,and finding an experimental basis on the study of molecular markers related to gastric cancer and screening high-risk groups of gastric cancer.ObjectiveWe analyzed the relationship between a 568 site A/G polymorphism in MUC1 gene and susceptibility to gastric cancer,as well as the effect of the A/G polymorphism on MUC1 protein expression.MethodsSequence specific primers-Polymerase chain reaction(PCR-SSPs)were performed to analyze the genotype of the A/G polymorphism in its 568 site of exon 2 for 138 gastric cancer cases and 241 non-cancer ones tested.Immunohistochemistry was used to detect the MUC1 protein expression for 71 gastric cancer cases and 191 non-cancer ones tested.Results1.The distribution frequency of AA,AG,GG three genotypes were 74.7%,21.2 %,4.1%respectively;2.The frequency of AA genotype was statistically higher in the gastric cancer(GC) group compared to the non-cancer group(84.1%Vs 74.7%,P=0.023),moreover, compared with individuals with MUC1 AG+GG genotype,individuals with AA genotype increased 1.81 fold risk for gastric cancer. 3.Compared with non-cancer group,the positive rate of MUC1 protein expression in gastric cancer group had statistically differences(P＜0.05);4.There were statistically negative-correlation between AA genotype of MUC1 gene and MUC1 protein expression in gastric mucosa(r=-0.1790,P=0.004).It was found that the rate of individuals with AA genotypes was decreased than AG+GG genotype ones in non-cancer group(P=0.000),OR value was 3.76(95%CI,1.87-7.53);but there was no statistically difference in gastric cancer group.Conclusion1.The frequency of AA genotype was statistically higher in the gastric cancer(GC) group;and it was benefit for the early diagnosis of gastric cancer to detect MUC1 genotype.2.There were statistically negative-correlation between AA genotype of MUC1 gene and expression of MUC1 protein,and 568 site A/G polymorphism of MUC1 gene could affect the expression of MUC1 protein.