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Association Of Thrombospondin-1,2 Single Nucleotide Polymorphisms Wigh Genetic Susceptibility To Gastric Cancer

Posted on:2011-04-28Degree:MasterType:Thesis
Country:ChinaCandidate:B B HongFull Text:PDF
GTID:2154360305484697Subject:Biochemistry and Molecular Biology
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Gastric cancer is one of the most devastating human cancer in worldwide, its occurrence is the result of many factors.Thrombospondins (THBS) is a multifunctional extracellular matrix glycoprotein, which serve to regulate the occureece and progression of cancer. This study investigates the role of THBS genes single nucleotide polymorphisms on the occurrence and progression of gastric cancer.This study provides theoretical basis and experimental data for clinical diagnosis, treatment and prognosis of gastric cancer.I Association between single nucleotide polymorphisms of THBS-1 and the occurrence and progression of gastric cancerA case-control study was conducted to explore the single nucleotide polymorphisms of THBS-1 genetic susceptibility to gastric cancer using the PCR-RFLP assay.The results were as follows:1.The frequency of TT,TC,CC genotype of THBS-1 rs1478605 was different in the gastric cancer group and the control group, compared to the CC genotype, the TT and TC genotype carriers would have higher risk to cancer with 1.6 fold[P=0.01, odd ratio (OR)=1.6,95% confident interval (CI):1.11-2.2].2. Using logistic regression to do a multivariate analysis, the THBS-1 rs3743125 TT genotype was more evidently associated with lymph node metastasis, after potential confounding effects adjusted.The OR value was 2.68 (95%CI:1.02-7.03),after adjustment gender,age and tumor size,and it was 2.71, (95%CI:1.0-7.33),after adjustment gender, age and depth of the invasion.3. Four haplotypes (CT,CC,TC,TT) of THBS-1 rs1478605;rs373125 were reconstructed by PHASE software.After adjustment using logistic regression for the potential confounding effects of gender and age,the frequency of TT and CT haplotype had significant difference in the gastric cancer group and the control group, especially the TT haplotype was significantly susceptible to gastric cancer (P<0.01, OR=3.32, 95%CI:2.14-5.17).The present study has shown that THBS-1 rs1478605 polymorphism might be associated with the occurrence of gastric cancer. The odd ratio for gastric cancer was increase in those who carried the TT and TC genotype relative to CC. THBS-1 rs3743125 polymorphism could be correlated to lymph node metastasis,and the TT genotype carriers had a higher risk to the metastasis of lymph node.Moreover,the TT and CT haplotype of THBS-1 was found to be more susceptible to the occurrence of gastric cancer.â…¡Association between single nucleotide polymorphisms of THBS-2 and the occurrence and progression of gastric cancerTHBS-2 rs1132742 locus was determined by the same method.The results were that when gastric cancer patients were grouped to the diffuse group and the intestinal group according to the criteria of Lauren, the genotype frequency was significant different from the intestinal group and the control, CC genotype carriers woule have higher susceptibility to intestinal-type gastric cancer (OR=3.1,95%CI:1.69-5.81),after adjustment using logistic regression for the potential confounding effects of gender and age,the homozygous was more evidently associated with the occurrence of intestinal-type gastric cancer. (OR=3.77,95%CI:1.9-7.49).Analyzed the association of the genetic difference with clinicopathologic feature in gastric cancer, the data showed that the genotype distribution was different in different histological group, the CC genotype carriers would be more suspectable to the tissue differenciation of gastric cancer. (OR=5.92,95% CI:2.44-14.37).The study has shown that THBS-2 rs1132742 polymorphism might be associated with the occurrence of gastric cancer. Compared to the TT genotype carriers,the CC genotype carriers would be more suspcetible to the intestinal-type gastric cancer,and was closely associated with tissue differentiation of gastric cancer.
Keywords/Search Tags:Stomach neoplasms, THBS-1 gene, THBS-2 gene, Polymorphism, single nucleotide, Haplotype
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