Chicago Center for Jewish Genetics Disorders - Cancer Genetics

Ashkenazi Jews and BRCA1 and BRCA2

Various studies have looked at the ethnic distribution of BRCA1 and BRCA2 mutations associated with breast and ovarian cancer. As mentioned in the BRCA1 and BRCA2 sections of this website, ethnic specific mutations have been seen in the Dutch and Icelandic populations among others. Also, three mutations in the BRCA1 and BRCA2 genes have been found to occur at an increased incidence in the Ashkenazi Jewish population. The incidence of all three mutations has been estimated at 2.5% (or 1 in 40) in the Ashkenazi Jewish population, compared to less than 1% in the general population. These three mutations are summarized in the following table:

Mutation	Gene	Incidence in the Ashkenazi Jewish population
185delAG	BRCA1	1%
5382insC	BRCA1	0.1 to 0.5%
6174delT	BRCA2	1.5%

Why do these three mutations occur more commonly in the Ashkenazi Jewish population than in the general population? These three mutations are thought to occur at such an increased incidence due to the joint effect of a founder effect and genetic drift. This means that these mutations are assumed to have originated in a common ancestor shared by many Ashkenazi Jews. Founder effect mutations for BRCA1 and BRCA2 mutations are seen in other populations as well, such as the Dutch, Icelandic, Swedish, and Japanese populations.

While the presence of these three mutations might seem to make the decision about testing clearer for an Ashkenazi Jewish woman, it might in fact complicate matters. For example, what if a woman of Ashkenazi descent has only one second-degree relative diagnosed with breast cancer at age 60 years? Although she has minimal family history, should she have genetic testing for the three BRCA1 and BRCA2 mutations? It is not clear if she would be considered at high enough risk to be offered genetic testing for these three mutations. Imagine another example of an Ashkenazi woman who has a much stronger family history of breast and ovarian cancer. Genetic testing for these three mutations might be offered. However, if the results are negative, more complete testing should be pursued by looking at the rest of the BRCA1 and BRCA2 gene for a mutation that might be responsible for the cancer seen in this family. It is possible that no mutations in either the BRCA1 of BRCA2 gene might be found. These are examples of difficult and complex situations that should be discussed in the context of genetic counseling. For more information regarding recommended guidelines for genetic testing, please refer to the ASCO guidelines.

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Reviewed By Wendy Rubinstein, MD, PhD, FACMG, Assistant Professor, Feinberg School of Medicine, Northwestern University, Medical Director, ENH Center for Medical Genetics