Structure of epidemiological studies on genetic susceptibility to environmental toxicants

Metabolic genes code for enzymes that are involved in conjugation and detoxification of environmental toxicants. Polymorphisms in these genes result in individual differences in susceptibility to carcinogens and therefore in differences in cancer risk. The most common study design used in the area of genetic susceptibility is the case-control study, because of both economic and logistic constraints. Since metabolic gene polymorphisms are germ line mutations that are present before the onset of the disease, this study design is applicable, and the assessment of the polymorphism can be performed after diagnosis. Since the polymorphism interacts with the exposure through type 2 gene-environment interaction, and in the absence of exposure the polymorphism alone has no effect on the risk of disease, the measurement of the relevant exposure is mandatory. Relevant exposures can be measured according to the classical epidemiological methods, or by means of specific biomarkers, and therefore biases and confounders have to be taken into account in both design and analysis of the study, like in classic epidemiologic studies.