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

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.