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Breast and Ovarian Cancer
  Genetic Diseases in Askenazi Jews

By Lauren John, MA, MLS

Reviewed By Adam Lowe and Beth Crawford, MS, CGC


 

Ashkenazi is the term used to describe Jews who have ancestors from Eastern or Central Europe. Today, there are Ashkenazi Jews all over the world and many are intermarrying. But for centuries, political and religious factors ensured their genetic isolation from the population at large.

As is the case with other groups who live, or lived, in relative isolation — such as the French Canadians and Icelanders — scientists theorize that most Ashkenazi Jews can trace their ancestry back to a small number of founders. The founder theory is of particular interest to geneticists because they theorize that even if just a few of these founders had a mutation, the mutation would become amplified in the population. This theory is supported by the fact that today people of Ashkenazi Jewish descent have a higher incidence of a number of specific mutations, for example mutations in the genes that increase the risk of developing breast and ovarian cancer, and mutations that cause the childhood neurological disease Tay-Sachs disease.

 
 
 

Origins of the Ashkenazi Jews

The word Ashkenazi is derived from the Hebrew word for "Germany". Today, the term is used to refer to Jews who have ancestors from Eastern or Central Europe, such as Germany, Poland, Lithuania, Ukraine, and Russia.

Scholars disagree about how the Jews, living for thousands of years in the Middle East, first arrived in Eastern Europe. Some theorize that Mediterranean Jews, ca. 800 AD, were invited by the emperor Charlemagne to settle the Germanic territories. Not all of the Jews traveled that far east, however. (A separate group, the Sephardic Jews descend from ancestors in Spain and North Africa.)

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Ashkenazi Jews Today

Today, in the aftermath of World War II and the Holocaust, most of the world's 10 million Ashkenazi Jews live in the United States, Israel, South America, South Africa, Australia and New Zealand. About 80 percent of the six million ethnic Jews in the United States are of Ashkenazi Jewish descent.

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Some Genetic Diseases are More Common in Ashkenazi Jews

Ashkenazi Jews are at greater risk of developing several genetic diseases rarely found in the population as a whole. For example, Type 1 Gaucher disease — a nonlethal condition in which the body lacks a gene regulating the breakdown of a particular kind of fat — is one of the more common genetic disorders among Ashkenazi Jews. An estimated one in ten Ashkenazi Jews is a carrier for Gaucher disease. Carrying one mutated gene for the disease will not cause symptoms. However, if both parents carry one mutated gene, there is a one in four chance that their children will inherit two Gaucher genes and develop the disease.

The childhood neurological disorder Tay-Sachs disease is also most commonly found in people of Ashkenazi descent; an estimated 1 in 31 Ashkenazi Jews carrying a gene for Tay-Sachs. Here again, both parents must have a copy of the mutated gene in order to pass on the disease to a child — and the child of two people who each carry one Tay-Sachs mutation has a one in four chance of receiving two mutated genes and developing the disease.

Recent studies have shown that people of Ashkenazi Jewish descent may be at greater risk for breast and ovarian cancer than the general population.
In addition, recent studies have shown that people of Ashkenazi Jewish descent may be at greater risk for breast and ovarian cancer than the general population. In 1995, scientists from the National Institutes of Health (NIH) discovered that a particular mutation in the breast cancer gene called BRCA1 was present in one percent of the general Jewish population. In comparison, the percentage of people in the general U.S. population that have any mutation in BRCA1 has been estimated to be between 0.1 to 0.6 percent. A follow up study in 1996 found two additional mutations (one in the BRCA 1 gene and one in another breast cancer gene called BRCA2) to have a greater prevalence in the Ashkenazi Jewish population, bringing the overall risk for carrying one of these three mutations to 2.3 percent.

 

Why Do Ashkenazi Jews Get More Genetic Diseases? The Founder Effect Theory

Most of today's Ashkenazi Jews descend from a group of perhaps only a few thousand people.
Stanford University geneticist Neil Risch explains the range of genetic diseases unique to the Ashkenazi Jewish population by theorizing that most of today's Ashkenazi Jews descend from a group of perhaps only a few thousand people the privileged Ashkenazi that lived 500 years ago in Eastern Europe. The poorer Ashkenazi Jews, says Risch, had fewer children that lived to adulthood and, as a result, they did not pass on as many genetic conditions. Geneticists refer to this relatively small group of ancestors as founders.

Given that until recently, both religious and political factors helped to ensure that Ashkenazi Jews married other Ashkenazi Jews, millions of people may be able to trace their ancestry directly to these founders. Thus, even if just a few founders had a mutation, the gene defect would become amplified in the population.

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Why Do Ashkenazi Jews Get More Genetic Diseases? The Beneficial Mutation Theory

Other geneticists theorize that diseases in Ashkenazi Jews have arisen because of hidden benefits linked to the inheritance of a single copy of a mutant gene.

People who carried the Tay-Sachs gene may have been resistant to tuberculosis.
For example, people with one copy of the Tay-Sachs gene were discovered to be resistant to tuberculosis, a condition common in the crowded ghetto conditions in which Ashkenazi Jews often lived. Geneticists theorize that the people who carried the Tay-Sachs gene may have survived better under ghetto conditions, whereas people without the gene would be more likely to die. As a result, the Tay-Sachs gene continued to be passed on in greater numbers in the Ashkenazi population.

Today, with the tuberculosis threat largely gone, the gene threatens the Ashkenazi population because it is linked to serious and fatal childhood illness. But, historically, the gene was passed on because, although it threatened the lifespan of some children, it protected larger numbers of Ashkenazi Jews of all ages who were at risk for tuberculosis.

Regardless of the origin of the mutations, people of Ashkenazi Jewish descent should be aware that they may be at increased genetic risk for certain conditions. This knowledge and screening has already decreased the number of children born with the fatal Tay Sachs disease by making carrier testing available to those who want to learn their status. Understanding these risks can lead to more accurate risk assessment, genetic testing, and preventive therapy.

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Related News
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APC mutation contributes to early phase of colorectal cancer in Ashkenazi Jews

References

Questions and Answers About Estimating Cancer Risk in Ashkenazi Jews. (2000). National Cancer Institute, Cancer Fact Sheet 3.60 http://cis.nci.nih.gov/fact/3_60.htm

Genetics and Ashkenazi Jewish Populations. (2000) University of Pittsburgh Department of Human Genetics (http://www.pitt.edu/~edugene/Genetics.html)

Risch, N. et al. (1995). Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population. Nature Genetics 9(2):152-9.

Questions and Answers for Estimating Cancer Risk in Ashkenazi Jews.(1997). National Cancer Institute, National Institutes of Health Backgrounder May 14. (http://rex.nci.nih.gov/massmedia/backgrounders/Ashkenazi.html)

Ashkenazi. Encyclopedia Britannica. Chicago, IL. (2000) . http://www.britannica.com/bcom/eb/article/6/0,5716,9956+1+9835,00.html

Malcom, S., ed. (1998). Founder effects in the Jewish populations of the world. Clinical Molecular Genetics Society Web Site and Notes From X-Linked and Population Genetics Courses. http://www.ich.ucl.ac.uk/cmgs/jewish.htm


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