Chicago Center for Jewish Genetics Disorders - Cancer Genetics

Ashkenazi Jews and Colorectal Cancer

Various studies have looked at the ethnic distribution of mutations associated with colon cancer syndromes. As mentioned in the Overview of Colon Cancer Syndromes section of this website, ethnic specific mutations are seen in the Finnish and Swedish populations among others. It is known that the colorectal cancer rates in the Ashkenazi Jewish population are disproportionately high and may be the highest of any ethnic group in the world. Studies have shown that mutations in the genes which increase a person’s risk for colon cancer have been found to occur at an increased incidence in the Ashkenazi Jewish population which may explain the high rates of colorectal cancer.

Although two hereditary colon cancer syndromes (HNPCC and “classic” FAP) are not more common in Ashkenazim in general, both have a connection to individuals of Ashkenazi Jewish heritage. A specific mutation in one HNPCC gene is found in 2-3% of all colorectal cancers in Ashkenazi Jews under the age of 60. It is rarely found in the general population, but is found in higher frequency in young Ashkenazi Jews with colorectal cancer. In those individuals diagnosed at age 40 years or younger, seven percent have been found to carry this mutation. On the other hand, it is found in less than 1% of Ashkenazim with colorectal cancer diagnosed over the age of 60. For more information about HNPCC, please read Hereditary Colon Cancers.

Another specific mutation for hereditary colon cancer syndromes is found in the Ashkenazim. A mutation in the Adenomatous Polyposis Coli (APC) gene, or the gene known to predispose to FAP, is found in 6% of Ashkenazi Jews and 1-2% of Sephardi Jews. With this mutation, the colorectal cancers do not have the typical features of FAP. But even without a family history, 10%-12% of Ashkenazi Jews with this mutation develop colorectal cancer. This is not different from the overall risk of colorectal cancer in Ashkenazi Jews. For an individual without a family history of colorectal cancer, it is not an important risk factor. On the other hand, 28% of Ashkenazi Jews with colorectal cancer and a family history of colorectal cancer have been found to have this mutation suggesting some role in familial cases of the disease. It does not however, explain the overall increased incidence of colorectal cancer in Ashkenazi Jews. For more information regarding FAP, please read Hereditary Colon Cancers.

Why do these two mutations occur more commonly in the Ashkenazi Jewish population than in the general population? These two mutations are thought to occur at such an increased incidence due to the joint result of two reasons. These mutations are assumed to have originated in a common ancestor shared by many Ashkenazi Jews, and due to isolation, homogenous mating, and small population size the mutations were able to maintain their frequency in other generations.

Genetic testing for colorectal cancer is complex and should be discussed in the context of genetic counseling. Individuals who are concerned about their risk for cancer or who may consider genetic testing should consult a comprehensive cancer risk clinic that can provide cancer risk assessment. To find a genetic counselor in your area, please visit www.ngsc.org/resourcelink.asp.

Reviewed by Gershon Locker, MD, Head, Division of Hematology and Oncology, Evanston Northwestern Healthcare 12/05.

This page last updated on January 18, 2006.