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Genetically Tailored Preventive Strategies: an Effective Plan for the Twenty-first Century?¹

Stanford University School of Medicine, Stanford, California 94305 [AW]

Abstract

A preventive strategy of considerable appeal would offer specific lifestyle changes and preventive interventions to people at increased cancer risk because of inherited susceptibility. The hope for such a strategy stems in part from the variation in risk among carriers of cancer-predisposing mutations. For example, despite the high risks of cancers of the breast and ovary among BRCA1 and BRCA2 mutation carriers, some 30% of these women are estimated to reach age 70 years without developing either cancer. We need to know what protects these women, compared with carriers who do develop these malignancies. Apart from chance, possible explanations include variation in type of mutation, in genotypes at other loci, or in potentially modifiable lifestyle characteristics. This article reviews our present knowledge about risks for cancers of the colorectum, female breast, and ovary in carriers of highly penetrant germ-line mutations of susceptibility genes. The paper also reviews our present knowledge about options for reducing these risks through changes in lifestyle, chemopreventive agents, and prophylactic surgery. It concludes with a discussion of what we need to know to offer those with inherited susceptibility safe, effective options for preventing these cancers and to provide a framework for deciding among the options.

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