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Volume 358:2796-2803 June 26, 2008 Number 26
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Polygenes, Risk Prediction, and Targeted Prevention of Breast Cancer
Paul D.P. Pharoah, Ph.D., Antonis C. Antoniou, Ph.D., Douglas F. Easton, Ph.D., and Bruce A.J. Ponder, F.R.S.

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ABSTRACT

Background New developments in the search for susceptibility alleles in complex disorders provide support for the possibility of a polygenic approach to the prevention and treatment of common diseases.

Methods We examined the implications, both for individualized disease prevention and for public health policy, of findings concerning the risk of breast cancer that are based on common genetic variation.

Results Our analysis suggests that the risk profile generated by the known, common, moderate-risk alleles does not provide sufficient discrimination to warrant individualized prevention. However, useful risk stratification may be possible in the context of programs for disease prevention in the general population.

Conclusions The clinical use of single, common, low-penetrance genes is limited, but a few susceptibility alleles may distinguish women who are at high risk for breast cancer from those who are at low risk, particularly in the context of population screening.


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From the Departments of Oncology (P.D.P.P., B.A.J.P.) and Public Health and Primary Care (A.C.A., D.F.E.), University of Cambridge; and the Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre (B.A.J.P.) — both in Cambridge, United Kingdom.

Address reprint requests to Dr. Pharoah at Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, United Kingdom, or at paul.pharoah{at}srl.cam.ac.uk.

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Related Letters:

Polygenes, Risk Prediction, and Targeted Prevention of Breast Cancer
Wilkins R. J., Teixeira L., Julien C., Guimiot F., Jernström H.
Extract | Full Text | PDF  
N Engl J Med 2008; 359:1406-1407, Sep 25, 2008. Correspondence

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