Correspondence (+links): Population Frequency of Germline BRCA1/2 Mutations Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Monday, August 22, 2016

Correspondence (+links): Population Frequency of Germline BRCA1/2 Mutations

Population Frequency of Germline BRCA1/2 Mutations

To the Editor:

Knowledge of BRCA1/2 mutation status plays an important role in multiple aspects of oncologic care.1 Inherited mutations in BRCA1/2 are highly penetrant for hereditary breast and ovarian cancer syndrome, with lifetime risks—dependent upon the gene and population—of 50% to 70% for breast and 15% to 55% for ovarian cancer.2 BRCA1/2 mutations also lead to increased risks of other malignancies, such as prostate, pancreatic, and male breast cancers, although penetrance is lower.
Germline BRCA1/2 testing has traditionally been guided by personal and family cancer history1; however, two developments are changing the landscape of BRCA1/2 testing. First, the increased use of tumor genomic sequencing is leading to identification of germline BRCA1/2 mutations in patients without typical personal or family histories.3 Tumor genomic sequencing panels that contain BRCA1/2 that do not subtract matched germline DNA are fundamentally opportunistic screenings of patients with cancer. Second, for populations with a high frequency of BRCA1/2 mutation carriers,4 screening of all individuals has been proposed.5 For consideration of population-based BRCA1/2 testing, the expected frequency of a positive result is a required piece of critical information.....

 Fig 1. Graphical representation of BRCA1/2 heterozygous population frequencies in Exome Variant Server (EVS) and Exome Aggregation Consortium (ExAC) databases.

 Furthermore, population frequencies and penetrance estimates obtained from patients with high-risk familial hereditary breast and ovarian cancer may not be applicable in the discussion of population-based BRCA1/2 testing.


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