title: Human CYP1B1 Leu432Val gene polymorphism: ethnic distribution in African-Americans, Caucasians and Chinese; oestradiol hydroxylase activity; and distribution in prostate cancer cases and controls.
abstract: Cytochrome P4501B1 (CYP1B1) is involved in the activation of many carcinogens and in the metabolism of steroid hormones, including 17beta-oestradiol (E2) and testosterone. We report a significant difference in the allele frequencies of two point mutations in the coding region of the CYP1B1 gene among Caucasian (n = 189), African-American (n = 52) and Chinese (Linxian) (n = 109) populations. A (C to G) transversion at position 1666 in exon 3, which results in an amino acid substitution of Leu432 to Val, was present in African-Americans with an allele frequency for Va1432 of 0.75, in Caucasians of 0.43, and in Chinese of 0.17. A (C to T) transition at position 1719 in exon 3, with no amino acid change (Asp449), appeared to be closely linked with the Val432 variant. Results using human lung microsomal preparations from individuals with the CYP1B1Val/Val and CYP1B1Leu/Leu genotypes indicate that Val432 variant may be a high activity allele and thus may contribute to the interindividual differences in CYP1B1 activity. Because CYP1B1 is involved in hormone and carcinogen metabolism, and given the disparate rates of prostate cancer among ethnic groups, we also evaluated the association of the CYP1B1 Leu432Val polymorphism with prostate cancer risk in a pilot case-control study. Among Caucasians, 34% of men with cancer (n = 50) were homozygous for the Val432 polymorphism, while only 12% of matched control subjects (n = 50) had this genotype. These preliminary data indicate that genetic polymorphisms in CYP1B1 might play an important role in human prostate carcinogenesis.
authors.affiliation: Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors.forename: Y M
authors.initials: YM
authors.lastname: Tang
authors.forename: B L
authors.initials: BL
authors.lastname: Green
authors.forename: G F
authors.initials: GF
authors.lastname: Chen
authors.forename: P A
authors.initials: PA
authors.lastname: Thompson
authors.forename: N P
authors.initials: NP
authors.lastname: Lang
authors.forename: A
authors.initials: A
authors.lastname: Shinde
authors.forename: D X
authors.initials: DX
authors.lastname: Lin
authors.forename: W
authors.initials: W
authors.lastname: Tan
authors.forename: B D
authors.initials: BD
authors.lastname: Lyn-Cook
authors.forename: G J
authors.initials: GJ
authors.lastname: Hammons
authors.forename: F F
authors.initials: FF
authors.lastname: Kadlubar
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D002681:China / Q000453:epidemiology; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011471:Prostatic Neoplasms / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C020120:estrogen 2-hydroxylase