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

Background:The p53mutation 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 CYP1A1and GSTM1was investigated by using allele-specific PCR in 115 prostate cancer (PCa) patients and 204 control patients.Results:The CYP1A1 Val/Valgenotype significantly increased the risk for PCa (OR = 2.6; 95% CI = 1.11–6.25) and the Ile/Valgenotype showed a similar tendency (OR = 1.4; CI = 0.86–2.29). Individuals with the GSTM1 (0/0)genotype demonstrated a slightly increased risk (OR = 1.3; CI = 0.82–2.04). The combination of the CYP1A1 Valallele and GSTM1(010) genotype was associated with a higher risk (OR = 2.3; CI = 1.18–4.48) than the CYP1A1Val allele alone. When cases were analyzed by age at initial diagnosis, the relative risks with both the CYP1A1Val allele and the GSTM1(0/0) genotype were higher in the young group than in the old group (CYP1A1; OR = 1.7, CI = 0.89–3.17: GSTM1; OR = 1.6, CI = 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 CI of 0.93–3.17 and in stages A and B, the OR was 0.8 with a CI of 0.40–1.62.Conclusions:These results suggest that CYP1A1and GSTM1polymorphisms are linked to a propensity for PCa development.