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Study On The Impact Of CYP1A1 MspI, CYP2E1 RsaI, And GSTM1 Polymorphisms On The Risk Of Lung Cancer-A Case-control Study

Posted on:2003-03-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:S D ChenFull Text:PDF
GTID:1104360092465552Subject:Epidemiologic
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Objective: To evaluate the correlation of polymorphisms with CYP1A1Mspl, CYP2E1 Rsal and GSTMi, and environmemtal factors such as smoking, alcohal drinking, tea drinking etc. independently and in combination with the the risk of lung cancer.Methods: A case-control study which included 91 cases of lung cancercollected from the First Affiliated Hospital of Sun Yat-sen University of Medical Sciences, Guangzhou Tumour Hospital and The Red Cross Hospital of Guangzhou, and 138 controls . All subjects were investigated with a uniform questionnaire. The contents of survey included general characteristics such as age, sex, education, etc; habit of smoking, alcohol, tea and special kinds of food such as vegetables, carrot, milk, bean products,fruit, meat, fish,etc; physical exercise; psycho-social factors; family history of lung cancer. Blood samples were collected from all cases and controls for detecting CYP1A1 Msal, CYP2E1 Rsal and GSTM, polymorphisms. The polymorphisms of CYP1A1 Msal, CYP2E1 Rsal and GSTMi were analyzed by PCR based RELP.Results:1. The frequencies of the m2ni2, niinii, n^mi genotypes of CYP1A1 Msal were 39.56%, 25.27%,32.97% respectively in the case group, and 28.26%, 33.33%, 38.41% respectively in the control group. There was no significant13different in frequencies of this three kinds of genotypes between the two groups (P>0.05).2. The risk of suffering from lung cancer was 5.38 times (95%CI 1.42-20.33) in individuals with C2C2 genotype of CYP2E1 Rsal as that in individuals with CiC2 genotype. The risk assocciated with QCi genotype was higher (OR= 1.71, 95%CI 0.95-3.07) than that with C2C2 genotype.3. The rate of GSTMl null(0/0) genotype was higher in the case group than that in control group, with the OR of 1.38(95%CI 0.80-2.38), but there was no statistical significant.4. The results showed that a combination of several genotypes was strongly associated with lung cancer. There was a synergistic interaction between the m2m2 genotype of CYP1A1 Mspl and GSTMl null(0/0) genotype on the elevated susceptibility to lung cancer, and the OR of this two genotypes, compared with minii of CYP1A1 and GSTMi(+/+), was 2.01(95%CI 0.86-4.88). We also observed a synergistic interaction effect between m2m2 genotype of CYP1A1 Msal and CiQ genotype of CYP2E1 Rsal on the risk of lung cancer, with the OR of 3.09(95%CI 1.09-8.72). The CiCi genotype of CYP2E1 Rsal with GSTMl null(0/0) genotype had 2.11-fold risk of lung cancer compared to the CiC2 genotype of CYP2E1 Rsal with GSTMl null(+/+) genotype, but there was no statistically significant difference(P>0.05). The odds ratio for the combination of m2m2 genotype of CYP1A1 Msal, CiCi genotype of CYP2E1 Rsal and GSTMl null(0/0) genotype was 3.68(95%CI 1.08-12.52).5. Although individual polymorphic gene was not associated with the development of lung cancer, the results of analysis on the combined effects between genes and environmental factors showed that there were synergistic interactions between certain genotypes and certain environmental exposures. The odds ratio of smoker with m2m2 genotype of CYP1A1 Msal compared with m2m2 genotype was 2.56(1.05-6.25); the odds ratios of smoker with CiCigenotype, with C1C2 genotype and nonsmoker with CiCi genotype of CYP2E1 Rsal compared with nonsmoker with C]€2 genotype were 3.63(1.37~34.97), 3.27(1.09-9.84), 2.58(0.96-6.91) respectively. The odds ratio of combination of smoking and GSTM1 null(0/0) genotype compared with nonsmoking with GSTM1 (+/+) genotype was 3.07(1.36-6.95), and that of smoker with GSTM1 (+/+) genotype was 2.88(1.22-6.78).The risk of developing lung cancer in smoker with m2m2 genotype of CYP1A1 and GSTMi null (0/0)genotype was significantly higher than that in smoker with minii genotype of CYP1A1 and GSTMi null(0/0) genotype(OR6.33, 95%CI 1.94-24.80). The odds ratio of smoking with m2m2 genotype of CYP1A1 and GSTMi null genotype compared with nonsmoking with m2m2 genotype and GSTMi (+/+) was 4.88(1.07-22.35).6. Alcohol drinking was strongly associa...
Keywords/Search Tags:CYP1A1 CYP2E1 GSTM1, Polymorphisms, Environmental factors, Lung cancer, Risk
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