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Gastric Cancer Risk In Relation To Environmental Factors, Genetic Polymorphism Of Cytochrome P450 2E1 And Expression Of P27 ~(Kip1)

Posted on:2004-08-16Degree:MasterType:Thesis
Country:ChinaCandidate:Y WangFull Text:PDF
GTID:2144360092495999Subject:Epidemiology and Health Statistics
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IntroductionIn recent decades, gastric cancer incidence has declined in most of the industrialized world. However, gastric cancer is estimated to be second in frequency worldwide and remains the most common cancer in developing countries. The absolute number of these tumors might increase in many countries because more such cancers can be expected as people live longer. Gastric cancer remains the leading cause of cancer mortality in several countries.It has been well known that the onset of gastric cancer is related closely to environmental factors and genetic factors. Among the environmental factors, dietary factors is important, which can influence the risk of cancer on different stages of the cancer formation. Among the genetic factors, susceptibility to cancer is a hot spot question in current studies on tumor. Because cytochrome P450 2E1 is involved in the metabolic oxidation of carcinogenic nitroso compounds, including N -nitrosoamines, interindividual differences in the metabolic capacity of CYP2El are assumed to be associated with cancer susceptibility. On the other hand, cell cycle regulation changes in most of tumors. We can regard tumors as a kind of cell cycle diseases. p27 protein is a main negative cell cycle regulator, meantime it is an important prognosis factor of tumors.With epidemiological methods and moleculor biological technique, the influence of environmental factors and genetic factors on the onset and biological behavior of gastric carcinoma was evaluated macroscopically and microscopically, which will be the foundation for further revealing the cause of gastric cancer and preventing the carcinoma.Materials and MethodsStudy PopulationCases were selected from affiliated hospital of China Medical University with pathologically confirmed diagnoses of gastric cancer during the periods from February,2002 to June,2002. Each had no history of radiation therapy or chemical therapy. Controls were selected during the same period as cases, with no history of malignant trmor or alimentary tract diseases. After cases and controls were identified,5ml whole blood were collected and transported to laboratory as soon as possible and stored at -74 centigrade.Epidemiological Data CollectionWe interviewed cases and controls using a standard epidemiological questionnaire. The collected information included demographic factors , detailed information about gastric cancer, family history of cancer, smoking and drinking history, dietary habits and so on.Laboratory AnalysisGenome DNA was extracted from 5ml whole blood using boiling methods. The DNA purity and concentration were determined by spec-trophotometric measurement of absorbance at 260/280 run. The Rsa I polymophism of CYP2E1 was detected by PCR - RFLP. The primerswere designed based on conferences. The expression of p27Klpl protein in gastric carcinoma were detected by immunohistochemical method technique.Statistical AnalysisThe relationship between gastric cancer and genetic polymorphisms of cytochrome P450 2E1 or positive rates of p27Klpl protein expression in gastric carcimoma was measured by chi - squire test. The environmental factors were evaluated using the multiple - variable Logistic regression models. All the analysis were conducted in SPSS 10.0.ResultsWe use a multi - variable stepwise Logistic model to screen the risk or preventive factors of gastric cancer. The results show that high intake of salt, sausage and fried food were the risk factors for gastric cancer,while consumption of tea was the protective factor for gastric cancer.There are three alleles of the cytochrome P450 2E1, thar is A (cl/clKB (cl/c2) and C ( c2/c2). The frequencies of the allele cl and c2 of CYP2E1 are 83. 3% , 16. 7% respectively in cases and 69. 8% ,30. 2% respectively in controls. Gastric cases were more likely to carry allele cl than controls(x2 =5.24 P<0.05).The expression of p27 protein in cases of gastric carcinoma were detected by immunostaining method. The positive rates of p27 protein expression in gastr...
Keywords/Search Tags:Gastric cancer, Environmental factors, Cytochrome P450 2E1, Genetic polymorphisms, Gegetic susceptibility, p27Kip1 protein
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