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The Study on Relationship between Genetic Polymorphisms of O~6-Methylguanine-DNA Methyltransferase Gene and Esophageal Cancer in Kazakh in Xinjiang

Author: YuLiang
Tutor: AiNiWaEr·TuMiEr;ZhangDaMing
School: Xinjiang University
Course: Zoology
Keywords: O ~ 6 - methylguanine - DNA methyltransferase (COMT) Single nucleotide polymorphisms Esophageal squamous cell carcinoma Kazak
CLC: R735.1
Type: Master's thesis
Year: 2009
Downloads: 13
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Abstract


Esophageal cancer (Esophageal Cancer, EC) occurs in malignant esophageal epithelium, the five-year survival rate is less than 10%, the prognosis is poor, and serious harm to the health of the people, ranked sixth in the esophageal cancer mortality worldwide, the world each year about 30 million people died in the EC, China is the incidence of esophageal cancer in the world and the countries with the highest mortality in some areas such as the provinces of Henan, Hebei, Shandong, Shanxi, Guangdong and Xinjiang Ili Kazak Autonomous Prefecture of esophageal cancer incidence highest in various types of tumors, the 2006 third national retrospective survey of death statistics, EC mortality rate ranks fourth after lung cancer, liver cancer, stomach cancer, visible esophageal cancer is one of the major hazards of the health of the Chinese population. O ~ 6 - methylguanine-DNA methyl transferase (O ~ 6-methylguanine-DNA methyltransferase, MGMT) is the most important direct repair enzymes in the human DNA repair system can repair an important class of mutagenic and cause carcinogen - an alkylating agent of the DNA sequence of O ~ 6 - methylguanine damage, thus avoiding DNA alkylation damage caused by the accumulation of mutations reduce the susceptibility of the tumor. With the deepening of the understanding of the people of the MGMT gene MGMT gene polymorphism with esophageal cancer has become a hot research scholars in recent years. Northern Xinjiang is one of China's high incidence of esophageal cancer, esophageal cancer incidence rate in the first of the various types of tumors, and has a significant national characteristics, which the Kazak up to 68.88/10 000, the Xinjiang Kazakh animal husbandry, population mobility rarely intermarried with the outside world, compared with the same genetic background and lifestyle, the Hasake ideal study object is the incidence of esophageal cancer molecular epidemiology and etiology school, and MGMT gene polymorphism in Xinjiang Kazakh esophageal the association has not yet been reported. Objective: To investigate O ~ 6 - methylguanine-DNA methyltransferase (MGMT) gene polymorphism and Xinjiang Kazakh esophageal cancer. MATERIALS AND METHODS: The study subjects: study of 160 cases in Xinjiang Kazakh were: 51 cases in Xinjiang Kazakh esophageal squamous cell carcinoma patients, average age (55.96 ± 9.59) years old, taken from the First Affiliated Hospital of Xinjiang Medical University, May 2005 January to December 2007 of esophageal cancer cases, all cases were confirmed by esophagoscopy examination, histopathological diagnosis of patients with esophageal squamous cell carcinoma, radiotherapy, chemotherapy and surgical treatment before blood sampling are unaudited; 109 cases of non-cancer control The average age (50.90 ± 11.16) years old, taken from the First Affiliated Hospital of Xinjiang Medical outpatient the Kazakh examination by healthy people, are diagnosed. Samples are early in the morning, fasting peripheral blood, genomic DNA was extracted with the classic phenol - chloroform method. Methods: The reference to a number of the literature and http://snp500cancer.nci.nih.gov the website and http://www.ncbi.nlm.nih.gov/SNP website, select the MGMT gene exon Codon 84C gt; T ( L84F) Codon 53C gt; the T (L53L), fifth exon Codon 143A gt; G (I143V), the promoter region Promoter 135G gt; the T, Promoter 485C gt; A total of five single nucleotide polymorphism (Single nucleotide polymorphisms, SNPs) sites, using polymerase chain reaction - restriction fragment length polymorphism (Polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP) technology to detect 160 cases in Xinjiang Kazakh peripheral blood samples ( MGMT gene five SNPs were genotyped, including 51 cases of esophageal squamous cell carcinoma and 109 cases of non-cancer control) conducted a case - control study. Results: each SNP genotype distribution differences in esophageal cancer and control groups had no significant (χ2 and P values ??were: 0.128,0.938; 2.120,0.346; 1.773,0.183; 2.440,0.295; 3.961,0.138); the heterozygous and homozygous mutant merged with the wild-type distribution between the two groups compare Promoter 485C gt; A difference was significant (χ2 = 3.845, P = 0.050), Promoter 485C gt; A allele in distribution between the two groups by the logistic model adjusted for age, sex, the difference was significant (P = 0.018); the five SNPs joint analysis, 0 mutant alleles and 1-10 mutant allele in the share of esophageal were 21.6% (11/51), 78.4% (40/51) in the control group were 37.6% (41/109), 62.4% (68/109), distribution differences between the two groups was significant resistance (χ2 = 4.078, P = 0.043), the logistic model, OR value of 2.632 (95% CI :1.127-6 .105) 1-10 mutant allele esophageal cancer risk is 2.632 times 0 mutant allele; five SNPs joint alleles with age stratified analysis, in the in ≦ 60-year-old crowd, the mutant allele and 1-10 mutant allele distribution differences in the the esophageal group and the control group was significant (χ2 = 5.756, P = 0.016), the logistic model, OR value of 3.411 (95% CI :1.204-9 .663), show in ≦ 60-year-old population ,1-10 mutant allele of the risk of esophageal cancer mutant allele 3.411 times. Conclusion: MGMT Gene Promoter 485C gt; A Kazak esophageal cancer, while the other four SNPs Kazak esophageal cancer may no significant association; the five SNPs joint role in Xinjiang Kazakh esophageal mutant allele the risk of esophageal cancer especially, in the in ≦ 60-year-old crowd.

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