ETHICAL AND SCIENTIFIC CONSIDERATIONS FOR CHEMOPREVENTION RESEARCH INCOHORTS AT GENETIC RISK FOR BREAST-CANCER

Identification of cohorts at genetic risk for cancer offers unique res earch opportunities to explore the steps in carcinogenesis, from the i nheritance of a predisposing mutation to the development of preinvasiv e lesions or overt malignancy, and to evaluate interventions to modula te the carcinogenic process. However, cancer prevention strategies for most inherited cancer predisposition syndromes are of unproven benefi t, and the potential for adverse psychosocial effects and employment o r insurance discrimination associated with genetic testing is substant ial. Thus testing for genetic cancer risk remains highly controversial , and the National Center for Human Genome Research and the American S ociety of Human Genetics advise DNA testing for presymptomatic identif ication of cancer risk only in the setting of a carefully monitored re search environment. The commercial availability of predictive genetic resting, particularly for inherited susceptibility to cancer, has focu sed attention not only on the urgent need for research in cancer preve ntion for cohorts at genetic cancer risk but also on ethical considera tions surrounding clinical prevention research in genetic risk groups. This paper addresses the interrelationship of ethical and scientific issues in conducting chemoprevention research in these cohorts, especi ally for those studies which require presymptomatic testing for specif ic gene mutations as a study entry criterion or as a criterion for str atification. Practical approaches to study design and implementation i ssues for chemoprevention research in genetic risk cohorts are discuss ed, emphasizing the interactions of ethical and scientific considerati ons at all levels of the research process. (C) 1997 Wiley-Liss, Inc.()