| Colorectal cancer (CRC) is one kind of the most common malignant digestive tract cancers in the world. It has been estimated that there are more than 500,000 new cases each year, and that the CRC is the third most common cancer (after lung and stomach) worldwide and the second one in developed countries (after lung). China is a nation with a relatively low incidence of CRC, which is the fifth or sixth most common cause of cancer death. But recently the incidence rate of CRC has increased especially in the developing world with the change to western dietary.Most epidemiological studies have reported that 70 percent of CRC could be explained by the environmental factors especially diet factors and tobacco smoke. However, not all the subjects with high-risk environmental exposure come to new CRC case, because CRC is the result of both effect of environmental factors and genetic susceptibility. Metabolizing enzymes are responsible for activation or detoxification of foreign carcinogens or anti-carcinogens, some of which are derived from diet or tobacco smoke. Most metabolic enzymes have inheritance polymorphisms. Different allele combinations explain the different activities of metabolic enzymes with different expression.We conducted a population-based case-control study in Jiashan County to explore the distribution of genetic polymorphisms of metabolic enzymes in normal population and the interaction between environment and metabolic enzymes polymorphisms on CRC. Furthermore, based on the study, we tried to set up two quantitative assessment models including environmental factors and metabolic enzymes polymorphisms, one for the screening of colon cancer and the other for rectal cancer. The models were applied to the primary population toevaluate these efficacies.Material and MethodsThe case and control groups originated from a CRC cohort-study population that has followed up sincelst May 1990. 140 survival individuals (57 cases of colon cancer and 83 cases of rectal cancer), who had been diagnosed with CRC during 1st May 1990 to 1st Sep. 2002, composed the case group in this analysis; 343 controls were random selected from cohort population. All of the controls alive never had neoplasm.A constructed questionnaire elicited information on the demographic condition, diet, and history of selected diseases, etc. 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 same time of interview, frozen by sodium citrate and stored at -20 centigrade degrees(C) refrigerator shortly after. Genomic DNA was extracted from whole frozen blood samples using improved salting out procedure. Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methods were applied to detect the genotypes of CYP 1A1 at T6235C site, CYP1A2 at C743A site, CYP2E1 at Pst I /Rsa I sites, EPHX1 4-exon and MTR at A2756G site. All PCR assays were done without knowledge of case or control status.The differences in distributions of demographic variables between case and control were examined by Pearson's x2 tests; odds ratio (OR) with 95% confidence intervals (95%CI) was used to measure the strength of associations of exposure variables with prevalence rate of CRC; The main statistical analysis was Unconditional Logistic Regression to control potential confounders and to attain crude and adjusted OR. The diet intake data in biased distributions were categorized into four groups based on the quartile of controls.Base on the above population-based case-control study, we tried to set up two quantitative assessment models to determine individuals risk and population risk for colon cancer and rectal cancer, respectively. The selected factors significant in statistics include risk factors and protective factors, environmental exposures and genetic polymorphisms. The models were applied to the primary population to evaluate these efficacies... |
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