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Human CYP1B1 Leu432Val gene polymorphism: ethnic distribution in African-Americans, Caucasians and Chinese; oestradiol hydroxylase activity; and distribution in prostate cancer cases and controls

Tang, Yong Minga; Green, Bridgett L.a; Chen, Gen-Fua; Thompson, Patricia A.a; Lang, Nicholas P.b; Shinde, Abhijitb; Lin, Dong-Xinc; Tan, Wenc; Lyn-Cook, Beverly D.a; Hammons, George J.a; Kadlubar, Fred F.a

Original Articles
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Cytochrome P4501B1 (CYP1B1) is involved in the activation of many carcinogens and in the metabolism of steroid hormones, including 17β-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 Val432 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 inter-individual 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.

aDivision of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, AR, USA, bDepartment of Surgical Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USA and cDivision of Tumor Etiology and Carcinogenesis, Cancer Institute, Chinese Academia of Medical Science and Beijing Union Medical College, Beijing, PR China

Received 14 June 1999; accepted 17 May 2000

Correspondence to Fred F. Kadlubar, Division of Molecular Epidemiology (HFT-100), National Center For Toxicological Research (HFT-100), 3900 NCTR Road, Jefferson, AR 72079 USA Tel: +1 870 543 7940; fax: +1 870 543 7773; e-mail: fkadlubar@nctr.fda.gov

After this work was presented (Proc Am Assoc Cancer Res 1998;58:4260) and the manuscript prepared for submission, Bailey et al. (Cancer Res 1998;58:5038–5041) published a similar method along with data on the distribution of genotypes in Caucasians and African-Americans and reported the Val432Val allele to be associated with oestrogen receptor positivity in breast cancer.

© 2000 Lippincott Williams & Wilkins, Inc.