Colon Info .... Additional ......
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cancer.org
Mutation discovered that causes colorectal cancer; test
developed to detect it.
Summary: Researchers at the Johns Hopkins Medical Institute
and the Howard Hughes Medical Institute have identified a genetic mutation that causes colorectal cancer in families. Johns Hopkins is offering testing for this mutation.
A new genetic mutation has been found that can double the risk of developing familial colon cancer (FCC) in
carriers over their lifetime. FCC accounts for an estimated 15-50 percent of the approximately 130,000 cases of colorectal cancers diagnosed each year.
The researchers, at Johns Hopkins Medical Institutions and the Howard Hughes Medical Institute, have found the mutation in over 6 percent of Ashkenazi Jewish people studied, making it the most common known
cancer gene found in a specific population. Ashkenazim (Jews of Eastern European ancestry) have a lifetime
risk of colorectal cancer of 9 to 15 percent; for those that have this mutation, their lifetime risk of developing
colon cancer is estimated to be 18 to 30 percent.
The researchers have developed a test to detect this new mutation and encourage any Ashkenazi Jewish person with a family history of the disease to be tested. The test, currently available only at Johns Hopkins, costs approximately $200.
HOW WAS THE STUDY PERFORMED AND WHAT DID IT FIND?
The researchers initially identified the mutation in a single Ashkenazi Jewish person. Believing the genetic
similarity of this group may provide insights into FCC, the researchers then studied 766 Ashkenazim and
found the mutation in over 6 percent of those studied. Next, the researchers studied blood and tissue samples
of 211 Ashkenazi Jewish colon cancer patients. They found that one in six of those patients who developed
cancer prior to age 66, and one in eight of those who developed colorectal cancer at any age, had the mutation.
The mutation was also found in nearly one-third of Ashkenazi patients with a family history of colorectal cancer.
HOW DOES THE MUTATION INCREASE THE RISK OF CANCER?
The mutation occurs in a cancer-causing gene called APC. APC has previously been linked to a less common
form of hereditary colon cancer known as familial adenomatous polyposis (FAP), in which affected family
members develop hundreds of precancerous polyps. Cancer will almost certainly develop in at least one of
these polyps during the lifetime of an affected person. This most recently discovered mutation is different from
the one that causes FAP.
The mutation itself causes no harm. According to Kenneth Kinzler, PhD, associate professor of oncology at Johns Hopkins and co-author of the study, the mutation causes the substitution of base, adenine, for another, thymine. Bases are the small molecules that form the letters of the genetic code and are linked together to form
DNA. While causing no direct effect on the DNA or the protein molecule it encodes, this substitution does
make it difficult for cells to accurately copy the DNA. Copying of a colorectal cell's DNA occurs every time it
reproduces to replace worn out cells. An error in this process can then lead to a more serious mutation, one
that is similar to mutations in people with FAP. It is this second mutation that actually causes the colorectal
cancer to form.
WHAT CAN INDIVIDUALS DO?
Colon cancer is a disease that, if found at an early stage, responds well to treatment. Therefore, if an Ashkenazi individual has a family history of colorectal cancer (defined as having at least one parent, sibling, or child with a history of either colorectal cancer or precancerous polyps), he or she should begin colorectal
cancer screenings at a younger age and have these more often than people at average colorectal cancer risk in
order to detect cancer at its earliest, most curable stage. A test is available for this specific mutation, and
high-risk individuals should consider obtaining it. (Call 410-955-4041 for information about the test.) Genetic
counseling should be obtained by anyone considering the test.
WHAT ARE THE IMPLICATIONS OF THIS FINDING?
More intensive screenings of people found to carry the mutation could find precancerous polyps and early
cancers which can be successfully treated. The researchers expect this would prevent about 90% of colorectal cancer deaths in this population.
For further information on colorectal cancer, call the American Cancer Society at 1-800-ACS-2345.
Source: Laken SJ, Petersen GM, Gruber SB, et al. Familial colon cancer in Ashkenazim due to a hypermutable
tract in APC. Nature Genetics, 1997:17;79-83. |
