Joint effect among p53, CYP1A1, GSTM1 polymorphism combinations and smoking on prostate cancer risk： an exploratory genotype-environment interaction study  

作　　者：Luis A. Quinones Carlos E. Irarrázabal Claudio R. Rojas Cristian E. Orellana Cristian Acevedo Christian Huidobro Nelson E. Varela Dante D. Cáiceres 

机构地区：[1]Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Faculty of Medicine, Biomedical Science Institute（ICBM）, University of Chile, lndependencia 1027, Santiago, Chile [2]Department of Urology, National Cancer Corporation, Chile, Capellán Abarzúa 027, Providencia, Santiago, Chile [3]Epidemiology Division, School of Public Health, Faculty of Medicine, University of Chile, lndependencia 939,Santiago, Chile

出　　处：《Asian Journal of Andrology》2006年第3期349-355,共7页亚洲男性学杂志（英文版）

摘　　要：Aim： To assess the role of several genetic factors in combination with an environmental factor as modulators of prostate cancer risk. We focus on allele variants of low-penetrance genes associated with cell control, the detoxification processes and smoking. Methods： In a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their prostate cancer risk. Results： The joint risk for smokers carrying Pro^＊ and MI^＊, Pro^＊ and GSTM1null or GSTM1 null and CYP1A1 MI^＊ variants was significantly higher （odds ratio [OR]： 13.13, 95% confidence interval [CI]： 2.41-71.36; OR： 3.97, 95% CI： 1.13-13.95 and OR： 6.87, 95% CI： 1.68-27.97, respectively） compared with that for the reference group, and for non-smokers was not significant. OR for combinations among p53cd72, GSTM1 and CYP1A1 M1 in smokers were positively and significantly associated with prostate cancer risk compared with non-smokers and compared with the putative lowest risk group （OR： 8.87, 95% CI： 1.25-62.71）. Conclusion： Our results suggest that a combination of p53cd72, CYP1A1, GSTM1 alleles and smoking plays a significant role in modified prostate cancer risk on the study population, which means that smokers carrying susceptible genotypes might have a significantly higher risk than those carrying non-susceptible genotypes.Aim： To assess the role of several genetic factors in combination with an environmental factor as modulators of prostate cancer risk. We focus on allele variants of low-penetrance genes associated with cell control, the detoxification processes and smoking. Methods： In a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their prostate cancer risk. Results： The joint risk for smokers carrying Pro^＊ and MI^＊, Pro^＊ and GSTM1null or GSTM1 null and CYP1A1 MI^＊ variants was significantly higher （odds ratio [OR]： 13.13, 95% confidence interval [CI]： 2.41-71.36; OR： 3.97, 95% CI： 1.13-13.95 and OR： 6.87, 95% CI： 1.68-27.97, respectively） compared with that for the reference group, and for non-smokers was not significant. OR for combinations among p53cd72, GSTM1 and CYP1A1 M1 in smokers were positively and significantly associated with prostate cancer risk compared with non-smokers and compared with the putative lowest risk group （OR： 8.87, 95% CI： 1.25-62.71）. Conclusion： Our results suggest that a combination of p53cd72, CYP1A1, GSTM1 alleles and smoking plays a significant role in modified prostate cancer risk on the study population, which means that smokers carrying susceptible genotypes might have a significantly higher risk than those carrying non-susceptible genotypes.

关 键 词：p53cd72 GSTM1 CYP1A1 genetic polymorphism prostate cancer risk SMOKING 

分 类 号：R737.25[医药卫生—肿瘤]