METABOLIC PHENOTYPES OF RETINOIC ACID AND THE RISK OF LUNG-CANCER

The metabolic activity of cytochrome P-450 enzymes has been associated with an increased risk of developing lung cancer. We found previously that all-trans retinoic acid is catabolized by these oxidative enzyme s, and that an inhibitor of this system discriminated between two popu lations of lung cancer patients. We examined the association between t his metabolic phenotype and the risk of lung cancer of 85 subjects. Th e area under the plasma concentration x time curve (AUC) was calculate d after a single oral dose of all-trans retinoic acid (45 mg/m(2)). Th e mean AUC for patients who had either squamous or large cell carcinom as was significantly lower than that of patients with adenocarcinomas (P = 0.0001) or control subjects (P = 0.01). Individuals with an AUC < 250 ng . h/ml had a greater likelihood of having squamous or large ce ll carcinoma (odds ratio = 5.93). This study suggests that the ''rapid '' catabolism of all-trans retinoic acid is linked to an increased ris k of squamous or large cell cancers of the lung.