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A Case-control Study On Environmental Exposure Factors And Metabolic Enzymes Genetic Polymorphisms Of Colorectal Cancer

Posted on:2004-09-08Degree:MasterType:Thesis
Country:ChinaCandidate:Q T JiangFull Text:PDF
GTID:2144360092490714Subject:Epidemiology and Health Statistics
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Colorectal cancer (CRC) is one kind of the most common malignant cancers in the world. There are approximately 550,000 new cases each year, and the age-standardized annual mortality is about 25-35 per 100,000 worldwide. In China, an estimated 14,000 new cases and 3.54 per 100,000 mortality occurred of CRC each year, accounting for 6.80% of all new cases of cancer and 5.29% of all cancer mortality. Based on the newest report, the mortality of CRC in city and country is 6.98 and 4.72 per 100,000, respectively. According to data from the investigate of malignant cancers, the age-adjusted mortality of CRC was about 22.62 and 22.70 per 100,000 in men and women in 1970S, and 26.3 and 18.6 per 100,000 during 1988 to 1992, which is highly over the national level.The incidence of CRC is ascribed to multiple factors and stages. Worldwide, the incidence rates vary approximately 20-fold, which could be explained by the environmental factors especially diet factors and the genetic susceptibility. However, cancer susceptibility may result from differences in the expression of metabolic enzymes, Metabolizing enzymes responsible for activation or detoxification of mutagenic xenobiotic, some of which are derived form diet or tobacoo smoke. The most important enzymes include glutathione-S transferases (GSTs), 5,10-methylenetetrahydrofolate reductase (MTHFR) and so on.To investigate risk factors between environment and metabolic enzymes polymorphisms for CRC, we conducted a population-based case-control study in Jiashan City.Material and MethodsThe case and control groups had an origin of a CRC cohort-study population. After about 12 years follow-up, 163 survival individuals, who had been diagnosed with CRC during 1st May 1990 to May 2002, composed the case group in this analysis; 400 participants were random selected form cohort population as health group. All of the controls alive never had neoplasm.A constructed questionnaire elicited information on the demographic and socio-economic condition, diet, history of selected diseases, family cancer history, occupation and psychological factors. All subjects were interviewed face-to-face by trained interviewers. For each food, amounts consumed were estimated according to models of the more frequently consumed foods for the accuracy of survey.Blood samples were taken at the time of interview or shortly after and stored at -20 centigrade degrees('C) refrigerator. Genomic DNA was extracted from whole frozen blood samples using improved salting out procedure. A multiplex polymerase chain reaction (PCR) method was used to detect the presence or absence of the GSTM1 and GSTT1 genes and a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methods was applied to analyze MTHFR genotypes at C677T and A1298T sites. All PCR assays were done without knowledge of case or control status.Pearson's x2 test was used to examine differences in demographic variables, Nonparametric Mannl - Whitney U test was applied for biased distributions of the data, Unconditional Logistic Regression model for simple factors or multi-factors models and Falconer method for estimation of heritability. All analyses were performed with SPSS for Windows 10.0 and SAS 6.12. Each categorized into four groups based on the distribution in controls.Results1. Environmental factors and CRC1.1 Life style and CRC Passive smoking (colleague) was a risk factor of colon cancer (OR=4.87) . While drinking deeper-well water was a protective factor of rectal cancer(OR=0.39,95%CI, 0.16-0.94).1.2 History of diseases, familial history of cancer and CRC There were an obvious time-effect of mucoid stool, intestinal polyposis, hepatitis B, and taking purgation medicine in relation to risk of colon cancer. The OR value was 28.84,7.69,6.98 and 13.00, respectively. History of mucoid stool, adenoma, and intestinal polyposis were all significant association with rectal caner. The OR value was 94.86,31.81 and 24.10, respectively. History of family cancer...
Keywords/Search Tags:Colorectal cancer (CRC), Case-control study, Environmental exposure, Metabolic enzymes, Genetic polymorphism, glutathione S-transferases (GSTs), 5,10-methylenetetrahydrofolate reductase (MTHFR)
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