Oral contraception and genetic factors in breast cancer: characteristics and limits of case-only studies

The analysis of the interaction between environmental and genetic factors i s a matter of increasing interest in cancerology. More particularly the dis covery of the BRCAx family and the high cumulated incidence of familial bre ast cancers related to mutations of these proteins raised the issue of the differential effect of long term and/or early exposure to oral contraceptiv es in the presence of these mutations. The classical case-control design as sumes the presence of a control group, which can be sometimes difficult to obtain from both the technical and ethical points of view. Case-only or cas e-case studies, which are based only on series of cases, making them appare ntly attractive, have been proposed to analyze more specifically the intera ction term. The aim of the present paper is to review and discuss the metho dological basis and main assumptions of the case-only design, and their app licability to breast cancer studies. The measure of the interaction between an environmental factor and a susceptibility genetic factor differs in an important aspect from the measure of the association between an environment al factor and acquired tumoral genetic factor; this aspect is reminded.