Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer

Citation
J. Watanabe et al., Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer, PHARMACOGEN, 10(1), 2000, pp. 25-33
Citations number
31
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOGENETICS
ISSN journal
0960314X → ACNP
Volume
10
Issue
1
Year of publication
2000
Pages
25 - 33
Database
ISI
SICI code
0960-314X(200002)10:1<25:AOCGPW>2.0.ZU;2-B
Abstract
Cytochrome P450 1B1 (CYP1B1) participates in the metabolic activation of a number of procarcinogens including benzo[a]pyrene and the hydroxylation of 17 beta-estradiol at the C-4 position, In this study, we investigated the a ssociation between CYP1B1 genetic polymorphism and breast or lung cancer in cidence. The Ala-Ser polymorphism at codon 119 in presumed substrate recogn ition site 1 was significantly associated with the incidence of breast or s quamous cell carcinoma of the lung, On the other hand, Leu-Val polymorphism at codon 432 did not show any association to the cancers. An allele contai ning both Ala and Leu simultaneously, comprised 75% of alleles among 315 Ja panese healthy controls, was significantly inversely associated with breast cancer incidence. When expressed in a recombinant system, this CYP1B1 cDNA showed the lowest 17 beta-estradiol 4-hydroxylase activity among four diff erent variant forms of CYP1B1, Thus, inter-individual differences in activa tion of procarcinogens or metabolism of oestrogen originating from genetic polymorphisms of the human CYP1B1 gene may contribute to the susceptibility of human cancers. Pharmacogenetics 10:25-33 (C) 2000 Lippincott Williams & Wilkins.