E. Taioli et al., MODELS OF INTERACTION BETWEEN METABOLIC GENES AND ENVIRONMENTAL EXPOSURE IN CANCER SUSCEPTIBILITY, Environmental health perspectives, 106(2), 1998, pp. 67-70
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.