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

Chikako Kiyohara, Tomio Hirohata, Satoru Inutsuka

研究成果: ジャーナルへの寄稿記事

116 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)18-24
ページ数7
ジャーナルJapanese Journal of Cancer Research
87
発行部数1
DOI
出版物ステータス出版済み - 1 1996

Fingerprint

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

これを引用

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

:: Japanese Journal of Cancer Research, 巻 87, 番号 1, 01.1996, p. 18-24.

研究成果: ジャーナルへの寄稿記事

@article{6dc2092eb7324e23a935df3d3f722ecd,
title = "The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene",
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.",
author = "Chikako Kiyohara and Tomio Hirohata and Satoru Inutsuka",
year = "1996",
month = "1",
doi = "10.1111/j.1349-7006.1996.tb00194.x",
language = "English",
volume = "87",
pages = "18--24",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene

AU - Kiyohara, Chikako

AU - Hirohata, Tomio

AU - Inutsuka, Satoru

PY - 1996/1

Y1 - 1996/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0030028660&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030028660&partnerID=8YFLogxK

U2 - 10.1111/j.1349-7006.1996.tb00194.x

DO - 10.1111/j.1349-7006.1996.tb00194.x

M3 - Article

C2 - 8609043

AN - SCOPUS:0030028660

VL - 87

SP - 18

EP - 24

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 1

ER -