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Cytochrome P450 1A1 And Glutathione S-Transferase M1 Polymorphisms And Susceptibility To Lung Cancer

Posted on:2005-01-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiFull Text:PDF
GTID:2144360125457592Subject:Respiratory medicine
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Lung cancer (LC) is one of the six most common malignant diseases in the world . Lung cancer accounts for 19% of all cancer and 29% of all death. It is the commonest cause of cancer death to human in China. It has the highest mortality rate, too. Epidemiological study have shown that tobacco smoking is the most important etiological factor in the development of this cancer, and the risk is at least 20 times higher in long-term smoker compare nonsmokers. but only less than 20% persons risk to get the cancer. Obvoursely, there is a big deference to individuals' susceptibility of this cancer. Recently, account of study shown there is a growing realization that the development of most cancers results from a complex interaction of both environmental and genetic factor. It is an important factor to lung cancer susceptibility of genetic polymorphism in the bioactivation of procarcinogens and detoxification of carcinogens. In the two fuction, CYPs and GSTs is the most important metabolize enzymes. The common polymorphism at the CYP1A1 gene nucleotide position 264 (T-C) and cause activity of the enzyme arise. Faction and deletion are the two polymorphisms for GSTM1 gene. The individual in deletion polymorphism produce a lot of enzyme without any normal function , and for this null allele are less efficient at conjugating and detoxifying specific substrate intermediates of carcinogens. The cancer risk were affected by polymorphic CYPs and GSTs together.We hypothesized that, with the mutation of CYP1A1 and GSTM1 gene, alterations of enzymes activities of CYP1A1 and GSTM1 caused by existing of genetic polymorphisms would raise the risk of lung carcinogenesis through disturbing bioactivation of procarcinogens and detoxification of carcinogens. And also may these polymorphisms contribute to the genetic basis of highlydistinguished and concordant geographical distribution of lung cancer in Henan Chinese people. To test our hypothesis, a retrospective case-control study was conducted to explore the associations, and then to provide informative evidences and useful methods for high-risk population screening, diagnosis and treatment. Materials and Methods:One hundred and three cases with lung cancer were recruited from the first and second affiliated hospital of Zhengzhou university, which were histopathologically confirmed from March to August in 2003. All cases were Chinese people from Henan areas and were investigated to exclude other simultaneous malignancies. One hundred and thirty-eight subjects with matched age and sex frequencies were randomly selected as control group from the same region in the field surveys between March and August in 2003.Genomic DNA was extracted from remnant liquid of blood clot or bronchoalveolar larage fluid (BALF) using protocols provided by Gentra Puregene DNA purification kit. Polymerase chain reaction (PCR) and PCR based restriction fragment length polymorphisms (PCR-RFLP) detection were applied to analyze genotypes of the polymorphisms. Retrospective case-control study was conducted and Fisher Exact x 2 test was adopted to check the accordance with Hardy-Weinberg equilibrium in the control group. For risk estimation, the risk was evaluated in terms of age-sex adjusted odds ratios (OR) and 95% confidence intervals (CD by unconditional logistic regression model. All of the statistical analyses were calculated by SPSS 10.0(USA) statistical software. (p<0.05 was regarded as significant) Results:1. For CYP1A1, the allele frequencies of ml were 28% and 43% in control and LC groups, respectively. For GSTM1, the allele frequencies of deletion were 44.2% and 61.2% in control and LC groups, respectively.2. The frequencies of CYP1A1 genotypes distribution were 52.3%, 39.1% and 8% for CYPlAlwl/wl ( A) , CYPlAlwl/ml (B) and CYP1A1 ml/ml( C ) in controls, respectively; For cases, the frequencies of CYP1 Al A, B, C, were 26.2%, 62.1% and 11.7% in individuals with LC, respectively. For GSTM1, frequencies of deletion were 44.2%. in controls, in cases with LC, fr...
Keywords/Search Tags:lung cancer, genetic polymorphism, genetic susceptibility, CYP 1A1, GSTM1
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