Is Angelina Jolie Good for the Jews?

I awoke on May 14th to emails from friends and family sending me links to Angelina Jolie's New York Times article about her decision to undergo preventive mastectomies because she is BRCA1 positive.  I identified with the article because, like Jolie, knowledge of my BRCA mutation put me on a collision course with the same decision.  

Jolie’s announcement and the attendant flurry of media attention has brought discussions about breast cancer risk and BRCA testing to virtually every kitchen table in America.  The Israeli press has also picked up the story and the ensuing public discussion has the potential for great impact in the Jewish community.  While only about 1 in 500 people in the general population carry a BRCA mutation, the risk is far higher in the Ashkenazi population, at roughly 1 in 40.  

Why so high for us?  The answer lies in history books.

Most Jewish breast cancer families have one of three so called “founder” mutations, each of which likely came from a common ancestor.  Scientists have tracked these genes through Jewish history, by examining the DNA as well as history books.   

The Babylonian conquest caused the first major Jewish dispersion out of the land of Israel to Mesopotamia in the year 586 BCE.  After several generations, some Jews returned to Israel but after the revolt against the Persians in the 4th century BCE, many migrated further north toward the Caspian Sea and began the further gradual migration into Europe.   Those who migrated North and West became the Ashkenazi Jews.   

The next major upheaval and Jewish migration was the destruction of the Second Temple in the year 70 CE, which resulted in settlements in Spain, Morocco and Northern Africa, which became the Sephardic population.  Until these Jews were expelled from Portugal and Spain in 15th Century, there was little intermarriage between Sephardic Jews and Jews in other parts of the world.

Against this historical backdrop we examine the presence of the three Jewish Founder mutations in different populations of Jews.

Scientists believe that the oldest mutation is 185delAG on BRCA1.  185declAG is believed to predate the destruction of the First Temple and the first Jewish Diaspora because of its prevalence in a variety of dispersed Jewish populations.   This mutation was carried North and West by the migration from Mesopotamia though Europe.  It occurs in about one percent of Ashkenazi Jews, whether they live in the United States, Europe or Israel.  It is less prevalent, although still common, in other Jewish populations.  

The second mutation, known as 6174delT, is a BRCA2 mutation and is the most prevalent of the three Jewish BRCA mutations occurring in about 1.4 percent of Ashkenazi Jews.  Genetic historians believe it comes from a common ancestor in medieval Europe because it is not common in any other Jewish populations.  

The third founder mutation, known as 5382insC on the BRCA1 gene, is far less common.  This mutation is linked to another tragic historical event because it is also common among non-Jewish women of Eastern Europe, especially in Russia and Poland.  Some call it the “pogrom” mutation and believe it may have been introduced into the Jewish community as a result of pregnancies following rapes somewhere between the 13th and the 19th centuries.  This mutation plays a more important role in the non-Jewish communities where it originated.  
  
Together, these three mutations are found in 2.5 percent of Ashkenazi Jewish women, either in Israel or in the U.S.  The high number of BRCA mutation carriers in the Ashkenazi population comes from many generations of marrying only within the community and a close sharing of the gene pool due to the religious and societal pressures of the time.  

Angelina Jolie’s decisive action was possible because she viewed her future cancer risk through the crystal ball of knowledge.  Unfortunately, many in our community lack this knowledge.  Current estimates are that 90% of people with BRCA mutations are not aware they are at risk.    My hope is that the public conversation sparked by Angelina Jolie’s decision to share her story will spark dialog within the Jewish community.  Too many women do not learn they are at risk until after they are diagnosed with cancer, and knowledge is the key to changing the paradigm.