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Mismatch Repair Gene hMLH1 A655g, T1151A Polymorphisms and Colorectal Cancer

Author: SongLei
Tutor: ZhouJianNong
School: Nanjing Medical University
Course: Oncology
Keywords: Colorectal Cancer hMLH1 gene A655G T1151A Val384Asp
CLC: R735.3
Type: Master's thesis
Year: 2010
Downloads: 38
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Abstract


Background Colorectal cancer is a common digestive tract cancer, one that, in recent years, with the changes in people's diet structure and the deterioration of the environment, the morbidity and mortality has increased year by year. Therefore, all the more in-depth study of colorectal cancer, the current study found that colorectal cancer development and wrong with the repair system (mismatch repair, MMR) gene mutation is closely related to human MMR system has been found mainly include hMSH2 , hMLH1, hPMS1, hPMS2, hMSH6 and hMSH3, hMLH1 and hMSH2 function is most important, hMSH2 and hMLH1 gene mutations account for more than 90% of all detected mutations. HMLH1 gene mutation and loss of heterozygosity for missense mutations and nucleotide deletion or insertion caused a frameshift mutation, lead to the hMLH1 protein changes of the tumor, this study by the hMLH1 gene 8,12 two exons, respectively, from the clinical pathological and epidemiological research to further understand the relevance of colorectal cancer. Objective To study the hMLH1 gene exon A655G polymorphic loci, 12 exons the T1151A (Val384Asp) role in the pathogenesis of colorectal cancer. Method hMLH1 gene exons, we extracted 135 healthy people, 115 patients with postoperative pathologic diagnosis of colorectal cancer patients peripheral blood DNA by PCR-DHPLC and DNA sequence analysis methods, statistical analysis of the case-control study The hMLH1 gene exon 8 A655G polymorphism and colorectal cancer incidence relationship. Exon 12 T1151A (Val384Asp) in a 1:2 matched case-control study design, collected three digestive tract tumor-prone areas in Jiangsu Province, 33 cases of new onset familial colorectal cancer patients with sporadic colorectal cancer 66 cases and 66 cases of peripheral venous blood of healthy people, and the application of PCR-DHPLC and DNA sequence analysis, analysis of hMLH1 gene in exon 12 T1151A; and bioinformatics software analysis Val384Asp. The hMLH1 gene A655G detection rate in the normal population, 3.0% to 11.3% (OR = 4.174,95% CI 1.322 ~~ 13.18) in colorectal cancer patients, the difference was statistically significant (P lt; 0.01); in colorectal cancer common pathological type of tubular / tubular papillary adenocarcinoma the A655G detection rate of 8.2%, and the The mucinous adenocarcinoma A655G detection rate was 27.8% (5/18) (OR = 0.2286, 95% CI 0.06488 ~ .8053) The difference was statistically significant (P lt; 0.05); lymph node metastasis whether the difference was statistically significant and specific type of pathology; younger age (lt; 50-year-old) and old age (≥ 50 years) between patients between gender difference was not statistically significant (P gt; 0.05). Detection rate of familial colorectal cancer patients Val384Asp patients with sporadic, and the difference between the normal controls was not statistically significant (P gt; 0.05); However, in elderly patients with familial ≥ 50 years of age in the detection rate was significantly higher than normal controls (P lt; 0.05), is in a critical value (P = 0.051) differences between patients with sporadic; bioinformatics software to analyze 384 Screenshot acid (Val) is one of the biological evolution The conserved sites, which was aspartic acid (Asp) replacement may affect protein function; corresponding sites of gene sequence T → A transversion may also affect the shear regulation. Conclusion hMLH1 gene exons 8 A655G polymorphism may affect the incidence of colorectal cancer, cell differentiation, and lymph node metastasis, suggesting that the hMLH1 gene A655G screening may become a risk assessment of patients with colorectal cancer prognosis indicators. 12 outside of the hMLH1 gene exon T1151A familial colorectal cancer genetic susceptibility factors, but is closely related to the incidence of elderly patients, further study of a large sample confirmed; Val384Asp pathogenic mechanisms may affect protein function and shear abnormalities.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Intestinal neoplasms
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