MODELS OF INTERACTION BETWEEN METABOLIC GENES AND ENVIRONMENTAL EXPOSURE IN CANCER SUSCEPTIBILITY

Polymorphic metabolic genes that confer enhanced genetic susceptibilit y to the carcinogenic effects of certain environmental carcinogens act according to a type 2 interaction between genetic and environmental r isk factors. This type of interaction, for which the gene has no effec t on disease outcome by itself but only modifies the risk associated w ith exposure, must be treated differently from other types of gene-env ironment interaction.We present a method to analyze different dose eff ects often seen in studies involving these genes. We define a low expo sure-gene effect, when a greater degree of gene environment interactio n appears at lower doses of exposure (the interaction follows an inver se dose function), and a converse high exposure-gene effect, when the interaction increases as a function of dose. Using a standard logistic regression model, we define a new term, ct, that can be determined as a function of exposure dose in order to analyze epidemiological studi es for the type of exposure-gene effect. These models are illustrated by the use of hypothetical case-control data as well as examples from the literature.