Polygenes, risk prediction, and targeted prevention of breast cancer

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.