Population Testing for High Penetrance Genes: Are We There Yet?

Recent technological advances make large-scale genetic testing possible. Current guidelines recommend testing in certain clinically affected individuals or those with strong family history (1). The successful use for high-risk groups has led many to con-sider extending genetic testing to the general population. In this issue, Manchanda and colleagues present a cost-effectiveness analysis of population-based testing for high-penetrance mutations associated with an increased risk of breast and ovarian cancer (2). They conclude that population-based testing of women age 30 years and older for a limited set of genes is more cost-effective for preventing death than genetic testing in women with a personal or a family history. This conclusion dif-fers from a previous cost-effectiveness analysis that did not find population-based BRCA1/2 testing to be cost-effective (3). The previous results were based on a decision-analysis model developed for an Ashkenazi Jewish population that was applied to the general population (4), while the new model was developed using general population estimates (2). We discuss oppor-tunities and challenges of population-based genetic testing and emphasize where additional evidence is needed. Several parameters are important when considering population-based are related to the mutations under for the maximum number of cases that possibly be prevented or detected early genetic It is estimated that 5% to 10% of and up to 15% of all ovarian to germline in BRCA1 and BRCA2 mutations contribu-tions