Use of relatives of cases as controls to identify risk factors when an interaction between environmental and genetic factors exists.

ABSTRACT

BACKGROUND: The difficulty in detecting relevant risk factors for chronic diseases (such as breast and colon cancer) may be due to heterogeneity in the populations of studied cases, and one source of heterogeneity may be differential genetic susceptibility predisposing to differential environmental sensitivity. METHODS: The purpose of this investigation is to determine whether the estimates of odds ratios are modified by using relatives as controls when risk factors interact with an underlying genetic factor. RESULTS: We demonstrate that using relative controls in matched case-control studies produces odds ratios different from population-based odds ratios. This difference is dependent on the amount of interaction between the genetic and environmental factors and on the genetic correlation between relatives. CONCLUSIONS: In the case of a common disease, the use of relatives as controls could be helpful in detecting interaction between an exposure and an underlying genetic factor when the genetic factor is common.