Cytochrome P4501A1 and Glutathione S-Transferase M1 Genotypes as Risk Factors for Prostate Cancer in Japan

Abstract

Background: The p53 mutation spectrum of prostate cancers developing in Japan indicates a role for environmental factors. This suggests there might be differences in susceptibility due to genetic polymorphisms in metabolic activation enzyme genes. We analyzed genetic polymorphisms of the xenobiotic-metabolizing enzymes, CYP1A1 and GSTM1. Method: Genotyping of CYP1A1 and GSTM1 was investigated by using allele-specific PCR in 115 prostate cancer (PCa) patients and 204 control patients. Results: The CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR = 2.6; 95% Cl = 1.11-6.25) and the IIe/Val genotype showed a similar tendency (OR = 1.4; Cl = 0.86-2.29). Individuals with the GSTM1 (0/0) genotype demonstrated a slightly increased risk (OR = 1.3; Cl = 0.82-2.04). The combination of the CYP1A1 Val allele and GSTM1 (0/0) genotype was associated with a higher risk (OR = 2.3; Cl = 1.18-4.48) than the CYP1A1 Val allele alone. When cases were analyzed by age at initial diagnosis, the relative risks with both the CYP1A1 Val allele and the GSTM1 (0/0) genotype were higher in the young group than in the old group (CYP1A1; OR = 1.7, Cl = 0.89-3.17: GSTM1; OR = 1.6, Cl = 0.84-2.99). The frequency of the GSTM1 (0/0) genotype was also higher in patients with advanced stage disease. In stage D, the OR was 1.7 with a Cl of 0.93-3.17 and in stages A and B, the OR was 0.8 with a Cl of 0.40-1.62. Conclusions: These results suggest that CYP1A1 and GSTM1 polymorphisms are linked to a propensity for PCa development.