How common are BRCA mutations in Ashkenazi Jews?
It is estimated that around 1 in 40 people of Ashkenazi Jewish ancestry are BRCA positive relative to 1 in 300-400 in the general population. BRCA-associated cancers are therefore seen more frequently in Jewish people of Ashkenazi descent.
The likelihood of an Ashkenazi Jew inheriting a BRCA mutation depends on a number of factors including:
- The strength of their Ashkenazi ancestry -people with four Ashkenazi Jewish grandparents have a higher risk than those with mixed Ashkenazi Jewish and non-Ashkenazi Jewish ancestry.
- The strength of their family history of breast, ovarian or prostate cancer – the number of family members who have developed cancer, the age at which they developed cancer and how closely related they are, are all contributing factors.
- Whether they have blood relatives with known mutations in a BRCA gene.
If you are Ashkenazi and are concerned about your risk, talk to your GP about your family’s cancer history, mentioning that you are of Ashkenazi origin. If appropriate, they will refer you to your regional genetics clinic where a genetic counsellor will provide you with support and information and will discuss with you whether genetic testing is an appropriate option.
Why are BRCA mutations more common in Ashkenazi Jews?
Ashkenazi Jews are descended from a small population of approximately 350 individuals who lived about 700 years ago. This means that Ashkenazi Jews share a greater proportion of their genetic makeup with one another relative to others in the general UK population. This is known as a founder effect and is particularly common in small populations or ethnic minorities where individuals tend to have children with others from the same population.
Due to the founder effect, Ashkenazi Jews not only share common traits but also mutations, including those in the BRCA genes. It is not the case that Ashkenazi Jews are more prone to genetic disease than other populations, rather that certain genetic conditions including BRCA-associated cancers are relatively more common in this population. A similar phenomenon is seen in other small populations and communities where other specific genetic conditions are common.
The risk of being a BRCA carrier is different for people with Sephardi ancestry, and this risk differs across different Sephardi populations (for example Iraqi Jews, Morrocan Jews, Libyan Jews etc)
What BRCA mutations have been identified in Ashkenazi Jews?
Three specific mutations within the BRCA1 and BRCA2 genes are thought to account for the majority of cases of hereditary cancer in Ashkenazi Jews. These three mutations are often called: 185delAG (also known as c.68_69delAG), 5382insC (also known as c.5266dupC), and 6174delT (also known as c.5946delT).
1 in 40 people of Ashkenazi Jewish ancestry are thought to carry one of these three mutations.
Although these mutations are more commonly found in Ashkenazi Jews, some are also present in a small proportion of individuals of non-Ashkenazi Jewish descent. It is also possible that Ashkenazi Jews could possess other mutations within the BRCA genes, or other cancer-associated genes.
Written by Jnetics.
Approved by Professor Rosalind Eeles Professor of Oncogenetics at The Institute of Cancer Research, The Royal Marsden Hospital London
Last review: 22.03.2021