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Cancer Risk Models: Translating Family History into Clinical Management

Susan M. Domchek, MD; and Antonis Antoniou, PhD
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From Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, and University of Cambridge, Cambridge CB1 8RN, United Kingdom

Potential Financial Conflicts of Interest: Dr. Domchek receives grant support from the Cancer Genetics Network. However, she was not involved in the preparation of Parmigiani and colleagues' manuscript, which was an ongoing project at the Cancer Genetics Network before she became the site principal investigator at the University of Pennsylvania.

Requests for Single Reprints: Susan M. Domchek, MD, University of Pennsylvania, 14 Penn Tower, 3400 Spruce Street, Philadelphia, PA 19104; e-mail, susan.domchek@uphs.upenn.edu.

Current Author Addresses: Dr. Domchek: Cancer Risk Evaluation Program, Abramson Cancer Center, University of Pennsylvania, 14 Penn Tower, 3400 Spruce Street, Philadelphia, PA 19104.

Dr. Antoniou: Cancer Research, United Kingdom Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, United Kingdom.

Ann Intern Med. 2007;147(7):515-517. doi:10.7326/0003-4819-147-7-200710020-00009
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BRCA1 and BRCA2 mutation carriers have a very high lifetime risk for breast or ovarian cancer. Because strategies to reduce these risks are effective (1), identifying appropriate individuals for genetic testing is very important. During genetic counseling, a professional obtains a detailed 3-generation pedigree, examines it to determine potential inheritance patterns, and decides whether to recommend genetic testing. The probability that a person has a BRCA1 or BRCA2 mutation is 1 factor in deciding about genetic testing and medical management. Researchers have developed statistical models that predict the absolute risk for breast and other types of cancer and estimate the probability of finding germline mutations in cancer susceptibility genes. In this issue, Parmigiani and colleagues (2) tested the ability of 6 of these models to discriminate BRCA1 and BRCA2 mutation carriers from noncarriers. The models included in the study, as well as several others (34), are in current use in cancer risk assessment programs (5).

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