Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer |
| |
Authors: | Watanabe J Shimada T Gillam E M Ikuta T Suemasu K Higashi Y Gotoh O Kawajiri K |
| |
Affiliation: | Laboratory of Cancer Diagnosis and Therapy, Saitama Cancer Center Research Institute Kitaadachi-gun, Japan. jwata@cancer-c.pref.saitama.jp |
| |
Abstract: | Cytochrome P450 1B1 (CYP1B1) participates in the metabolic activation of a number of procarcinogens including benzo[a]pyrene and the hydroxylation of 17beta-estradiol at the C-4 position. In this study, we investigated the association between CYP1B1 genetic polymorphism and breast or lung cancer incidence. The Ala-Ser polymorphism at codon 119 in presumed substrate recognition site 1 was significantly associated with the incidence of breast or squamous 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 containing both Ala and Leu simultaneously, comprised 75% of alleles among 315 Japanese healthy controls, was significantly inversely associated with breast cancer incidence. When expressed in a recombinant system, this CYP1B1 cDNA showed the lowest 17beta-estradiol 4-hydroxylase activity among four different variant forms of CYP1B1. Thus, inter-individual differences in activation of procarcinogens or metabolism of oestrogen originating from genetic polymorphisms of the human CYP1B1 gene may contribute to the susceptibility of human cancers. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|