The relationship between CYP1A1 aryl hydrocarbon hydroxylase activity and lung cancer in a Japanese population

Chikako Kiyohara, Yoichi Nakanishi, Satoru Inutsuka, Koichi Takayama, Nobuyuku Hara, Akira Motohiro, Keitaro Tanaka, Suminori Kono, Tomio Hirohata

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Because aryl hydrocarbon hydroxylase (AHH) is considered to be responsible for the activation of benzo(a)pyrene and other polyaromatic hydrocarbons in cigarette smoke to carcinogens, it is important to examine CYP1A1 (AHH) activity in the determination of susceptibility to lung cancer. We investigated AHH activity in peripheral mitogen-treated lymphocytes in 108 lung cancer patients and 95 healthy control individuals. Non-induced AHH activity was detectable in all the samples. AHH inducibility (3-methylcholanthrene-induced/non-induced AHH activity) showed a very wide interindividual variation as well as non-induced AHH activity. No significant associations were found between adjusted AHH activity and histologic type of tumor among lung cancer patients. Adjusted AHH inducibility of genotype C [geometric mean and 95% confidence interval (CI); 15.56 and 11.69-20.71] in MspI polymorphism was significantly higher than those of the other two genotypes (P = 0.0001), while no significant difference was observed between genotypes A (4.76 and 3.82-5.93) and B (5.60 and 4.57-6.86). On the other hand, non-induced AHH activity of genotype Val/Val (0.121 and 0.082-0.178 pmol/min/106 cells) in isoleucine-valine (Ile-Val) polymorphism was significantly higher than those of genotypes Ile/Ile (0.042 and 0.034-0.052 pmol/min/106 cells) and Ile/Val (0.040 and 0.030-0.053 pmol/min/106 cells) (P < = 0.0001). Even after controlling for age, cigarettes smoked per day and season of the year, high AHH inducibility (7.0 < versus 0 < ≤ 3.0: OR and 95 %CI, 12.4 and 2.88-53.4) was an independent risk factor for lung cancer. The data indicate that high AIM inducibility may strongly associate with the susceptibility to lung carcinogenesis.

Original languageEnglish
Pages (from-to)315-323
Number of pages9
JournalPharmacogenetics
Volume8
Issue number4
DOIs
Publication statusPublished - 1998

All Science Journal Classification (ASJC) codes

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

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