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Risk Stratification in Cancer Predisposition Syndromes: Lessons Learned from Novel Molecular Developments in Li-Fraumeni Syndrome

¹ Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children and ² Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Requests for reprints: David Malkin, Division of Hematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Phone: 416-813-5348; Fax: 416-813-5327; E-mail: david.malkin{at}sickkids.ca.

Key Words: Cancer predisposition, risk, telomere, genetic modifier • Predictive assays for carcinogenicity • DNA damage and repair mechanisms • Risk assessment • p53

Germ-line mutations in specific genes predispose family members to cancer. Prediction of the exact tumor type and timing of cancer initiation is fundamental to the development of management strategies for these individuals. Recent advances in our understanding of the general processes that control cancer initiation may enable us to tailor more precise risk stratification. This, in turn, will lead to more effective early detection strategies, which would result in more favorable clinical outcomes. In this review, we highlight the steps and methods used to reach this futuristic model. [Cancer Res 2008;68(7):2053–7]

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