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
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
- Hereditary Diffuse Gastric Cancer: Caused by mutation in the CDH1 gene associated with stomach, lobular breast and colon
- 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
- Von Hippel Lindau Syndrome: Hereditary mutation of VHL gene
associated with an increased risk of kidney cancer and benign blood vessel
- 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.