Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer

The development of prostate cancer is dependent on heredity, androgenic inf luences, and exposure to environmental agents. A high intake of dietary fat is associated with an increased risk of prostate cancer, either through in fluence on steroid hormone profiles or through production of carcinogenic c ompounds that require biotransformation by enzymes. The polymorphic glutath ione S-transferase (GST), N-acetyltransferase (NAT), and cytochrome P450 (C YP) enzymes are of particular interest in prostate cancer susceptibility be cause of their ability to metabolize both endogenous and exogenous compound s, including dietary constituents. Association between different NAT2, CYP2 D6, CYP2C19 and GSTP1 genotypes and prostate cancer was studied in a Swedis h and Danish case-control study comprising 850 individuals, The combined Sw edish and Danish study population was analysed by polymerase chain reaction for the NAT2 alleles *4, *5A, *5B, *5C, *6 and *7, and for the CYP2D6 alle les *1, *3 and *4. The Swedish subjects were;also analysed for the CYP2C19 alleles *1 and *2, and the GSTP1 alleles *A, *B and *C. No association was found between prostate cancer and polymorphisms in NAT2, CYP2D6, CYP2C19 or GSTP1, An association between CYP2D6 poor metabolism and prostate cancer w as seen among smoking Danes; odds ratio 3.10 (95% confidence interval 1.07; 8.93), P = 0.03, but not among smoking Swedes; odds ratio 1.19 (95% confid ence interval 0.41; 3.42), P = 0.75. Smoking is not a known risk factor for prostate cancer, and the association between CYP2D6 poor metabolism and pr ostate cancer in Danish smokers may have arisen by chance. Pharmacogenetics 9:333-340 (C) 1999 Lippincott Williams & Wilkins.