[Metabolic polymorphisms and the cancer risk: the evaluation of epidemiological studies]

Abstract

Genetic modulation of environmental exposures associated with common malignancies is an attractive mechanism to explain differential susceptibility to tobacco or occupation-related carcinogens in the population. The paper reviews the evidence for an association between three genetically based metabolic polymorphisms (N-acetyltransferase, Debrisoquine, hydroxylase, aryl hydrocarbon hydroxylase), which have been implicated in the modulation of lung or bladder cancer risks. Fair to good support emerged for both an association of the acetylation phenotype with occupationally related bladder cancer and for an association of the debrisoquine metabolic phenotype with lung cancer, although in neither case was the evidence completely convincing. Epidemiologic evidence for an association between aryl hydrocarbon hydroxylase and lung cancer is presently problematic because of the difficulties in the assay and subsequent confounding factors.