Population Estimates of the Likelihood of Having a BRCA1 or BRCA2 Mutation
Statistics regarding the percentage of individuals found to be BRCA mutation carriers among samples of women and men with a variety of personal cancer histories regardless of family history are provided below. These data can help determine who might best benefit from a referral for cancer genetic counseling and consideration of genetic testing, but cannot replace a personalized risk assessment, which might indicate a higher or lower mutation likelihood based on additional personal and family history characteristics.
In some cases, the same mutation has been found in multiple apparently unrelated families. This observation is consistent with a founder effect, wherein a mutation identified in a contemporary population can be traced back to a small group of founders isolated by geographic, cultural, or other factors. Most notably, two specific BRCA1 mutations (185delAG and 5382insC) and a BRCA2 mutation (6174delT) have been reported to be common in Ashkenazi Jews. However, other founder mutations have been identified in African Americans and Hispanics.[43,44,45] The presence of these founder mutations has practical implications for genetic testing. Many laboratories offer directed testing specifically for ethnic-specific alleles. This greatly simplifies the technical aspects of the test but is not without limitations. For example, it is estimated that up to 15% of BRCA1 and BRCA2 mutations that occur among Ashkenazim are nonfounder mutations.
Among the general population, the likelihood of having any BRCA mutation is as follows:
- General population (excluding Ashkenazim): about 1 in 400 (~0.25%).[20,46]
- Women with breast cancer (any age): 1 in 50 (2%).
- Women with breast cancer (younger than 40 years): 1 in 10 (10%).[48,49,50]
- Men with breast cancer (any age): 1 in 20 (5%).
- Women with ovarian cancer (any age): 1 in 8 to 1 in 10 (10%-15%).[52,53,54]
Among Ashkenazi Jewish individuals, the likelihood of having any BRCA mutation is as follows:
- General Ashkenazi Jewish population: 1 in 40 (2.5%).
- Women with breast cancer (any age): 1 in 10 (10%).
- Women with breast cancer (younger than 40 years): 1 in 3 (30%-35%).[56,57,58]
- Men with breast cancer (any age): 1 in 5 (19%).
- Women with ovarian cancer or primary peritoneal cancer (all ages): 1 in 3 (36%-41%).[60,61,62]
Two large U.S. population-based studies of breast cancer patients younger than age 65 years examined the prevalence of BRCA1[49,63] and BRCA2 mutations in various ethnic groups. The prevalence of BRCA1 mutations in breast cancer patients by ethnic group was 3.5% in Hispanics, 1.3% to 1.4% in African Americans, 0.5% in Asian Americans, 2.2% to 2.9% in non-Ashkenazi Caucasians, and 8.3% to 10.2% in Ashkenazi Jewish individuals.[49,63] The prevalence of BRCA2 mutations by ethnic group was 2.6% in African Americans and 2.1% in Caucasians.