| Objective:To investigate the relationship between environmental agents and the methylation and polymorphisms of GSTP1, RASSF1A in the deveolpment of prostate cancer (Pea).Methods:A 1:2 case-comrol study was conducted. The patients of prostata cancer identfied pathologically were selected as cases. Community-based population and the patients of other disease in the hospital were recruited as controls. One huandred and forty one cases and 282 controls were included in this study. A questionnaire was used to collect the demographic and environmental data for both of cases and controls. Conditional Logistic Regression Medel was adopted in the analysis of data. Odds Ratio (OR) as well as the 95% Cofident Interval (95%CI) were computed to estimate the exposure risk of environmental factors. First, the univariate analysis (α=0.05) was used to select the statistically significant factors. Then, along with other related factor in terms of specialty, these significant variables were included in the multivariate models so as to obtain relatively independent influence factors by adjusting the confounders. The GSTP1 and RASSF1A genotypes were determined by the method of TaqMan/MGB Probe Technology in 85 patients with Pea and 80 normal controls. Methylation-specific PCR with SYBR Green was used to detect the degree of methylation of GSTP1 and RASSF1A in 88 patients with Pea and 169 normal controls. Multivariate unconditional logistic regression model was introduced to assess the susceptibility of methylation and genetic polymorphism in the development of Pea. Environmental agents were also included in the analysis such as smoking, alcohol drinking.Results:(1) 1:2 case-control study 1:2 case-control study revealed twelve independent risk facotrs realted to the occurrence of PCa, which included the facotrs of life style, dieting, personnel chacracter and psychology. These factors are drinking (OR=2.06, 95%CI=1.06-3.95), family history of prostate caner (OR=10.33,95% CI=2.45-43.48), self-bearing character (OR=1.83,95%CI=1.07-3.12), living apart with spouse (OR=2.16,95%CI=1.27-3.67), intake of fish(OR=3.70,95%CI=2.16-6.34), intake of poultry (OR=2.68,95% CI=1.15-6.24), cabbage (OR=2.00,95%CI=1.08-3.70), cauliflower (OR=2.04,95% CI=1.15-3.59), barbecue (OR=5.62,95% CI=2.38-13.27), tea drinking (OR=0.37,95% CI=0.21-0.66), physical exercise (OR=0.44,95% CI=0.26-0.74) and stewing of cooking (OR=0.45,95%CI=0.27-0.76).(2) Genepolymorphism, environmental factors and Pca The frequencies of the GSTP1 AA,AG and GG genotypes distribution were 64.70%, 24.70%, and 10.60% in patients of prostate cancer and 71.20%,27.50%, and 1.20% in controls respectively. The difference between the two groups was significant statistically (P=0.042). The frequencies of genotypes of CC. CA and AA of RASSF1A were 89.40%,7.10%, and 3.50%in patients of prostate cancer and 85.00%,12.50%, and 2.50% in controls respectively. The difference between the two groups was not significant statistically (P=0.556).(3) Gene methylation, environmental factors and Pca1.The MI of the whole blood DNA methylation of patient's with prostate cancer was significantly higher than that of controls.2.Gene methylation and environmental factors with interaction in the development of prostate cancer.Conclusion:Our results indicate that the abnormal methylations of GSTP1 and RASSF1A are related to the development of prostate cancerthe. The factors of drinking, living apart with spouse, intake of poultry, cabbage, barbecue, tea drinking, physical exercise and stewing of cooking are associated with the occurrence of abnormal methylation. The development of good habits are helpful in the preventing and controling of prostate ccancer such as physical exercise, tea drinking and stewing of cooking. The polymorphisms of GSTP1, RASSFIA are not associated with the development of Pca in Chinese Han nationality. The detection of methylation of GSTPland RASSFIA in blood has potential application in the clinical diagnosis and screening of prostate cancer.
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