Why Is Hereditary Breast Cancer So Common Among Ashkenazi Jews?

Ashkenazi Jews are known as a community that lived in Eastern Europe for centuries and, before that, in the Caspian region, south of present-day Russia, in Azerbaijan, Armenia, Georgia, and northern Iran. Before the Jewish genocide (Holocaust), they made up four-fifths of the world’s Jewish population; today their share has fallen to about half. After World War 2, many migrated to present-day Israel. Karl Marx, Albert Einstein, Steven Spielberg, and Sigmund Freud are notable historical figures said to be Ashkenazi Jews. Although Jewish communities now live in many parts of the world, Ashkenazi Jews remained geographically isolated in Eastern Europe for centuries. This also resulted in relatively little genetic diversity.

In this community, genetic changes in ancestors were passed down and preserved through generations. High rates of changes in the BRCA1 and BRCA2 genes have been observed among Ashkenazi Jews. BRCA1 and BRCA2 genesare responsible for hereditary breast and ovarian cancer syndromes. Consequently, Ashkenazi Jews have an increased risk of breast and ovarian cancer. According to American disease control data, BRCA1 or BRCA2 gene mutations occur in one in every 40 Ashkenazi Jewish individuals. In the general population, the figure is 1 in 800 people.

Three mutations are most common in Ashkenazi Jewish individuals: 2 in BRCA1 and 1 in BRCA2, making 3 in total. It is important to emphasize that women with a BRCA1 or BRCA2 gene mutation may have a lifetime risk of breast canceras high as 85 percent. In individuals without these mutations, this risk is 12 percent. The lifetime risk of ovarian cancer reaches 40 percent in mutation carriers, compared with 1.8 percent in other individuals.

Researchers have also investigated other mutations that increase cancer risk in Ashkenazi Jewish communities. A study published in July 2017 performed genetic analyses in Ashkenazi Jewish individuals without the 3 typical mutations to identify mutations in other genes. The research team was led by Mary-Claire King, who discovered the BRCA gene. The genes of 1007 Ashkenazi Jewish women with breast cancer were sequenced.

According to the study findings:

• The 3 mutations typical of Ashkenazi communities were not found in 903 patients.
• Among these 903 patients, 7 had different mutations in the BRCA1 and BRCA2 genes. Dangerous mutations in breast cancer-associated genes such as CHEK2, BRIP, and NBN were identified in 31 patients. Because the study covered only known breast cancer-associated genes, genetic changes in the other individuals remain incompletely understood.

One of the most important findings of this study was the identification of cancer risk-increasing mutations in genes other than BRCA1 and BRCA2 in the Ashkenazi Jewish community.

The history of cancer predates even human history: signs of cancer have been identified in dinosaur fossils. Based on current knowledge, no community has ever been entirely free of cancer. Moreover, a greater prevalence of certain gene abnormalities in some communities increases cancer risk in those communities. Therefore, cancer develops as a result of gene mutations, rather than according to country or nationality.

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