Detection of interaction involving identified genes: available study designs

Advances in molecular genetic techniques have led to an increased ability to examine gene–environment interactions. Studies to detect gene–environment interactions are moti-vated by different situations, including 1) most identified cancer genes having associated lifetime risks less than 100% (i.e., incomplete penetrance), 2) hereditary factors that con-trol the metabolism of carcinogens that may modulate risk of disease as hypothesized in pharmacogenetics, and 3) incon-sistent associations across studies between a cancer and a suspected risk factor. The above situations and others have led to increased study of interaction between genetic and environmental factors. Less studied so far, but with in-creased potential for the future, is interaction between iden-tified genes. Gene–gene interaction studies would also be motivated by the situations described above. Approaches t