Human CYP1B1 Leu(432)Val gene polymorphism: ethnic distribution in African-Americans, Caucasians and Chinese; oestradiol hydroxylase activity; and distribution in prostate cancer cases and control

Cytochrome P4501B1 (CYP1B1) is involved in the activation of many carcinoge ns and in the metabolism of steroid hormones, including 17 beta -oestradiol (E-2) and testosterone. We report a significant difference in the allele f requencies of two point mutations in the coding region of the CYP1B1 gene a mong Caucasian (n = 189), African-American (n = 52) and Chinese (Linxian) ( n = 109) populations, A (C to G) transversion at position 1666 in exon 3, w hich results in an amino acid substitution of Leu(432) to Val, was present in African-Americans with an allele frequency for Val(432) Of 0.75, in Cauc asians of 0.43, and in Chinese of 0.17. A (C to T) transition at position 1 719 in exon 3, with no amino acid change (Asp(449)), appeared to be closely linked with the Val(432) variant. Results using human lung microsomal prep arations from individuals with the CYP1B1(Val/Val) and CYP1B1(Leu/Leu) geno types indicate that Val(432) variant may be a high activity allele and thus may contribute to the interindividual differences in CYP1B1 activity. Beca use CYP1B1 is involved in hormone and carcinogen metabolism, and given the disparate rates of prostate cancer among ethnic groups, we also evaluated t he association of the CYP1B1 Leu(432)Val polymorphism with prostate cancer risk in a pilot case-control study, Among Caucasians, 34% of men with cance r (n = 50) were homozygous for the Val(432) polymorphism, while only 12% of matched control subjects (n = 50) had this genotype. These preliminary dat a indicate that genetic polymorphisms in CYP1B1 might play an important rol e in human prostate carcinogenesis. Pharmacogenetics 10:761-766 (C) 2000 Li ppincott Williams & Wilkins.