ABSTRACT
Cytochrome P450 (CYP)1A1 gene polymorphism has been shown to be associated with several diseases. In this study, we evaluated the association between the polymorphism in the cytochrome P-450 (CYP)1A1 (CYP1A1) gene and genetic susceptibility to prostate cancer (PCa) in Tunisian men. One hundred and thirty eight PCa patients and the same number of controls were enrolled in this study. All DNA samples from peripheral blood leucocytes were genotyped for genetic polymorphism of the CYP1A1 gene using the polymerase chain reaction-restriction fragment length polymorphism method. The polymorphism in PCa patients was also analyzed according to age at diagnosis, tobacco use, cancer stage, and grade (Gleason score). The prevalence of CYP1A1 variants (w1m1 and m1m1) was similar in PCa patients and controls (15.22% vs. 17.39%, p=0.624 and 2.17%, respectively). No significant difference in the frequency distribution of CYP1A1 polymorphism was observed between PCa patients and controls. Furthermore, we were unable to demonstrate any significant association between the studied CYP1A1 polymorphism, age, tobacco use, and tumor parameters of aggressiveness at diagnosis.
Subject(s)
Cytochrome P-450 CYP1A1/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Prostatic Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Neoplasm Staging , Prevalence , Prostatic Neoplasms/enzymology , Prostatic Neoplasms/epidemiology , Risk Factors , Smoking/adverse effects , Smoking/epidemiology , Smoking/genetics , Tunisia/epidemiologyABSTRACT
Prostate cancer (PCa) formation has been reported to be associated with androgen. Two key steps in the sex steroid synthesis are mediated by the enzyme cytochrome P450c 17α which is encoded in the CYP17 gene. The A2 allele of the CYP17 gene has been thought to be associated with increased functional activity of this steroidogenic enzyme. Consequently, the A2 allele has been examined as a biomarker of individual susceptibility to hormone-related diseases among men. We prospectively assessed the association between the A2 allele of CYP17 and PCa risk among 125 cases and 125 controls in a case-control study. Our aim was to investigate whether a polymorphism of CYP17 gene could be used as a genetic marker for associating PCa. The result revealed a significant association between the CYP17 polymorphic genotypes and PCa. Therefore, CYP17 gene polymorphism is likely contributed to the pathogenesis of PCa but not to disease severity.
Subject(s)
Genetic Predisposition to Disease , Polymorphism, Genetic/genetics , Prostate/metabolism , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/genetics , Steroid 17-alpha-Hydroxylase/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Case-Control Studies , DNA/genetics , Genotype , Humans , Immunoenzyme Techniques , Male , Middle Aged , Neoplasm Grading , Polymerase Chain Reaction , Prognosis , Prospective Studies , Prostate/pathology , Risk Factors , Tunisia/epidemiologyABSTRACT
UNLABELLED: Several genes involved in the metabolism of carcinogenesis have been found to be polymorphic in the human population, and specific alleles are associated with increase risk of cancer of various sites. This study is focused on the polymorphic enzymes glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) that involved in the detoxification of many xenobiotics involved in the etiology of prostate cancer. OBJECTIVE: To evaluate whether GSTM1 and/or GSTT1 contribute to prostate cancer (CaP) etiology, we studied 110 incident CaP cases and 122 controls. RESULTS: The probability of having CaP was increased in men who had homozygous deleted (non-functional) genotypes at GSTT1 (OR=2.17; 95% CI=1-3.79) but not GSTM1 (OR=0.89; 95% CI=0.66-1.88). Hence, individuals lacking the GSTT1 gene are at approximately twofold higher risk of developing prostate cancer in comparison with individuals with at least one active allele in the GSTT1 locus. CONCLUSION: These results suggest that GSTT1 is associated with CaP risk. The effect of smoking associated with the GSTT10/0 genotype was not found to affect the risk of prostate cancer.
