The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene

Chikako Kiyohara, Tomio Hirohata, Satoru Inutsuka

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

We examined the relationship between aryl hydrocarbon hydroxylase (AHH) and the frequency of a MspI mutation in the 3'-flanking region of cytochrome P450 (CYP) 1A1 (MspI polymorphism) and another mutation in exon 7 (Ile-Val polymorphism) in 84 healthy male subjects in Fukuoka, Japan. AHH inducibility (3-methylcholanthrene (MC)-induced AHH activity/non-induced AHH activity) was correlated with the MspI polymorphism (P < 0.0001) and age class (P = 0.015), whereas no correlation was found for the Ile-Val polymorphism (P = 0.509). Age-adjusted AHH inducibility (mean ± SE) of the predominant homozygote (genotype A), the heterozygote (genotype B) and a homozygote rare allele (genotype C) genotypes was 4.89 ± 0.36, 4.82 ± 0.29 and 13.61 ± 1.44, respectively. The genotype C showed much higher AHH inducibility than genotypes A and B (P < 0.001), while no significant difference was observed between genotypes A and B. Non-induced AHH activity was also correlated with these polymorphisms. The AHH activity of a homozygous mutant Val/Val genotype (0.076 ± 0.010 pmol/min/106 cells) was significantly higher (P < 0.05) than that of the wild-type homozygous Ile/Ile (0.044 ± 0.004 pmol/min/106 cells) and heterozygous Ile/Val (0.047 ± 0.007 pmol/min/106 cells) genotypes. Our study suggests that the genotypes C and Val/Val, which are more frequent in smoking-related lung cancer, are closely related with high AHH inducibility and high non induced AHH activity, respectively. Thus, the positive relationship between AHH inducibility and lung cancer is supported by our study. If our results are confirmed and the assessment of genotype becomes feasible on a population basis, identification of smokers who have genetically high susceptibility to lung cancer (genotype C or Val/Val) may become important for the prevention of lung cancer.

Original languageEnglish
Pages (from-to)18-24
Number of pages7
JournalJapanese Journal of Cancer Research
Volume87
Issue number1
DOIs
Publication statusPublished - Jan 1 1996

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Aryl Hydrocarbon Hydroxylases
Cytochrome P-450 CYP1A1
Genotype
Genes
isoleucylvaline
Lung Neoplasms
Homozygote
3' Flanking Region
Mutation
Methylcholanthrene
Heterozygote
Cytochrome P-450 Enzyme System
Exons
Healthy Volunteers
Japan

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene. / Kiyohara, Chikako; Hirohata, Tomio; Inutsuka, Satoru.

In: Japanese Journal of Cancer Research, Vol. 87, No. 1, 01.01.1996, p. 18-24.

Research output: Contribution to journalArticle

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