THE RELATIONSHIP BETWEEN CYP1A1 ARYL-HYDROCARBON HYDROXYLASE-ACTIVITYAND LUNG-CANCER IN A JAPANESE POPULATION

Because aryl hydrocarbon hydroxylase (AHH) is considered to be respons ible for the activation of benzo(a)pyrene and other polyaromatic hydro carbons in cigarette smoke to carcinogens, it is important to examine CYP1A1 (AHH) activity in the determination of susceptibility to lung c ancer. We investigated AHH activity in peripheral mitogen-treated lymp hocytes in 108 lung cancer patients and 95 healthy control individuals . Non-induced AHH activity was detectable in all the samples. AHH indu cibility (3-methylcholanthrene-induced/non-induced AHH activity) showe d a very wide interindividual variation as well as non-induced AHH act ivity. No significant associations were found between adjusted AHH act ivity and histologic type of tumor among lung cancer patients. Adjuste d AHH inducibility of genotype C [geometric mean and 95% confidence in ternal (CI); 15.56 and 11.69-20.71] in MspI polymorphism was significa ntly higher than those of the other true 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/10(6) 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 /10(6) cells) and Ile/Val (0.040 and 0.030-0.053 pmol/min/10(6) cells) (P < 0.0001). Even after controlling for age, cigarettes smoked per d ay and season of the year, high AHH inducibility (7.0 < versus 0 < les s than or equal to 3.0: OR and 95% CI, 12.4 and 2.88-53.4) was an inde pendent risk factor for lung cancer. The data indicate that high AHH i nducibility may strongly associate with the susceptibility to lung car cinogenesis. Pharmacogenetics 8:315-323 (C) 1998 Lippincott-Raven Publ ishers.