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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / enzymology
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Adenocarcinoma / epidemiology
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Adenocarcinoma / genetics
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Aryl Hydrocarbon Hydroxylases*
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Breast Neoplasms / enzymology
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Breast Neoplasms / epidemiology
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Breast Neoplasms / genetics*
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Carcinoma / enzymology
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Carcinoma / epidemiology
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Carcinoma / genetics*
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Carcinoma, Large Cell / enzymology
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Carcinoma, Large Cell / epidemiology
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Carcinoma, Large Cell / genetics
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Carcinoma, Small Cell / enzymology
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Carcinoma, Small Cell / epidemiology
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Carcinoma, Small Cell / genetics
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Carcinoma, Squamous Cell / enzymology
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Carcinoma, Squamous Cell / epidemiology
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Carcinoma, Squamous Cell / genetics*
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Catalysis
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Cytochrome P-450 CYP1B1
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Cytochrome P-450 Enzyme System / genetics*
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Cytochrome P-450 Enzyme System / metabolism
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Estradiol / metabolism
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Female
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Gene Frequency
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Genetic Variation
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Genotype
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Humans
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Incidence
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Japan / epidemiology
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Lung Neoplasms / enzymology
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Lung Neoplasms / epidemiology
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Lung Neoplasms / genetics*
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Male
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Polymorphism, Genetic / genetics*
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Polymorphism, Single-Stranded Conformational
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Reference Values
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Risk Assessment
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Steroid Hydroxylases / metabolism
Substances
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Estradiol
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Cytochrome P-450 Enzyme System
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Steroid Hydroxylases
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Aryl Hydrocarbon Hydroxylases
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CYP1B1 protein, human
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Cytochrome P-450 CYP1B1