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Correlation between Genetic Polymorphisms of Cytotoxic T Lymphocyte-Associated Antigen-4 Gene and Susceptibility to Esophageal Cancer

Author: ChengXiaoLi
Tutor: ChenZiPing
School: Shandong University
Course: Internal Medicine
Keywords: Cytotoxic lymphocyte-associated antigen 4 Esophageal tumors Haplotype Tag SNP Association studies
CLC: R735.1
Type: Master's thesis
Year: 2011
Downloads: 30
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Abstract


Background and purpose of esophageal cancer is one of the common human malignancies, China is a high incidence of esophageal countries, the mortality rate is among the first in the world to explore a long time about the etiology of esophageal cancer, there has never been conclusive, recent studies have raised the esophagus cancer is the existence of a high degree of penetrance susceptibility genes. Cytotoxic T lymphocyte-associated antigen 4 is a T lymphocyte activation important negative regulator of anti-tumor immune T cells play an important role. Moreover, existing studies suggest that the CTLA4 Ji Yinte positioning point polymorphisms affect the function of CTLA4. Therefore, this study discusses the CTLA4 gene rs231775, rs4553808 and rs733618 three tagSNP site polymorphisms and susceptibility to esophageal cancer and the biological behavior of the association, screening of esophageal cancer risk genetic markers in the high incidence of esophageal and perform gene therapy may provide an important basis. Methods 237 cases and 408 cases of normal control group design as research subjects, case-control study of patients with esophageal squamous cell carcinoma. Subsequently, selected 205 cases of esophageal cancer patients as case group, and select the case group of the same sex, as a control group of healthy individuals of the same age, 1:1 matched case-control study in order to better control for confounding factors. Extract each individual venous whole blood 3ml, genomic DNA was extracted. PCR-RFLP (?) Kyrgyzstan aggregate direct sequencing of the CTLA4 gene on three tagSNPs for genotyping using Haploview 4.1 software for linkage analysis, respectively, to a non-conditional logistic regression model and conditional logistic regression model analysis in group design and matching the design of the relationship of the three sites of the CTLA4 gene polymorphisms and susceptibility to esophageal cancer. PHASE 2.1 software based on Bayesian algorithm to construct the haplotype analysis of haplotype and susceptibility to esophageal cancer. Chi-square test or the exact analysis three tagSNP sites TNM staging of esophageal cancer. Results in the group case-control design, the the rs231775 locus AG and AA genotype increased the risk of esophageal cancer (P lt; 0.003, adjusted OR = 1.823,95% CI, :1.233-2 .693; P = 0.003, adjusted OR = 2.053 , 95% CI :1.277-3 .298). Similarly, rs4553808 locus AG genotype to esophageal cancer risk increased approximately 2-fold (P lt; 0.001, adjusted OR = 2.267,95% CI, :1.589-3 .233), and rs4553808 locus genotypes in esophageal different TNM Staging The crowd in the period, the overall distribution of the difference was statistically significant (P = 0.002). Rs231775 sites AG and AA genotype matched case-control study design to increase the risk of esophageal cancer (P = 0.001, adjusted OR = 2.280,95% CI, :1.433-3 .629; P = 0.008, adjusted OR = 2.192,95 % CI :1.229-3 .911), rs4553808 locus AG genotype to esophageal cancer risk increased by 1.8 times (P = 0.004, adjusted OR = I.848, 95% CI :1.220-2 .800). Linkage analysis between rs231775, rs4553808 and rs733618 locus linkage disequilibrium (0.5 lt; D 'lt; 0.8), to further build the eight kinds of haplotypes using PHASE 2.1 software haplotype AAG distribution in the case group higher than those in the control group (P = 0.005), increase esophageal cancer risk (OR = 5.035,95% CI, :1.599-15 .860). Haplotype GAA in the distribution of the control group was significantly higher than that of the case group (P = 0.001). After adjustment for risk factors like smoking, can reduce esophageal cancer risk (OR = 0.413,95% CI :0.251-0 .680). Conclusion CTLA4 gene rs231775, rs4553808 two loci polymorphisms and susceptibility to esophageal cancer related haplotype analysis the AAG can increase the risk of esophageal cancer, and reduce the risk of esophageal cancer in GAA, rs4553808 locus polymorphisms with esophageal cancer TNM staging.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Esophageal tumors
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