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/10(6) cells) was significantly higher (P < 0.05) than that of the wild-type homozygous Ile/Ile (0.044 +/- 0.004 pmol/min/10(6) cells) and heterozygous Ile/Val (0.047 +/- 0.007 pmol/min/10(6) 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.