Other Hereditary Cancers

In addition to having increased rates of BRCA mutations, Ashkenazi Jews have among the highest rates of colorectal cancer (CRC) of any ethnic group. In the general population, the lifetime risk of CRC is approximately five percent. In Ashkenazi Jews, this risk is two to three times greater. Approximately 10 percent of colorectal cancer is hereditary. Two known genetic syndromes account for a significant proportion of hereditary colorectal cancer: familial adenomatous polyposis (FAP) and Lynch syndrome, also called hereditary non-polyposis colon cancer (HNPCC). The mutations associated with these syndromes are inherited in an autosomal dominant pattern, which means affected individuals have a 50% chance of passing on the gene mutation to the next generation. Learn more about cancer risk assessments. 

Familial Adenomatous Polyposis (FAP)

FAP accounts for approximately one percent of all colorectal cancer. Classic FAP is characterized by a preponderance of polyps, early age of onset of polyps, and virtual certainty of developing colon cancer. It is caused by mutations in a tumor suppressor gene called APC. One specific APC mutation (I1307K) is found in approximately six percent of Ashkenazi Jews. This mutation does not cause classic FAP, but it does lead to a twofold increase in colon cancer risk. Ashkenazi Jews with I1307K APC mutations have a 10 to 20% lifetime risk of colorectal cancer when there is no family history of CRC. Colon polyps may develop, but in far fewer numbers than in classic FAP. The slight increase in risk of colon cancer in carriers does not warrant routine genetic screening for this mutation or prophylactic surgery.  

Lynch Syndrome

Lynch syndrome accounts for approximately five percent of colorectal cancer cases. Lynch syndrome is sometimes referred to as hereditary non-polyposis colorectal cancer or HNPCC. It is caused by mutations in one of several genes that repair errors in DNA. People with this condition have a greatly increased chance of developing colorectal cancer and other cancers, especially at a young age. Other cancers associated with Lynch syndrome include stomach cancer, endometrial cancer and ovarian cancer. 

There are many other cancer syndromes caused by inherited mutations. In general they are not increased in Jewish people compared to the general population.

• Hereditary Diffuse Gastric Cancer: Caused by mutation in the CDH1 gene associated with stomach, lobular breast and colon cancer
  
• Li Fraumeni Syndrome: Hereditary mutation of the TP53 gene associated with sarcomas, brain tumors, leukemia, adrenal and breast cancers
  
• Cowden Syndrome: Hereditary mutation of the PTEN gene associated with breast cancer, thyroid (follicular) cancer and endometrial cancer
  
• Von Hippel Lindau Syndrome: Hereditary mutation of VHL gene associated with an increased risk of kidney cancer and benign blood vessel tumors
  
• Multiple Endocrine Neoplasm Syndrome: Associated with increased risk of tumors of the endocrine organs (pancreas, thyroid, pituitary, adrenal) which can be benign or malignant

Still curious about hereditary cancer?
The Center’s genetic counselor can answer your questions or to refer you to the appropriate organization or a genetic counselor in your area.