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Last Updated: Nov 17th, 2006 - 22:35:04
Research Article
New England Journal of Medicine

Colon Channel
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Latest Research : Cancer : Colon

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Check Colon Tumors for Signs of Syndrome - Study
May 7, 2005, 18:51, Reviewed by: Dr.

“It's important that people who have this syndrome know they have it because there is a good chance we can prevent cancer from developing or at least detect it early when it is more easily treated.”

 
A new study suggests that, after surgery, all colon tumors should be tested to learn if the patient may have an inherited syndrome that carries an extremely high risk of cancer. It also suggests that this prescreening can be done using a relatively inexpensive microscopy test already used in hospital pathology laboratories.

The study showed that two to three percent(at least one in 45) of people with colon cancer probably have mutations for the inherited syndrome, known as Lynch syndrome (also known as hereditary nonpolyposis colon cancer, or HNPCC).

Prescreening for Lynch syndrome will help determine if the person and his or her relatives should consider genetic counseling and testing for the syndrome. In addition, the test might help doctors better estimate a patient's long-term prognosis.

The study, led by researchers with The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, is published in the May 5 issue of the New England Journal of Medicine.

Lynch syndrome is caused by a mutation in one of four genes. One out of two first-degree relatives of those with the syndrome are also likely to have the mutations.
“It's important that people who have this syndrome know they have it because there is a good chance we can prevent cancer from developing or at least detect it early when it is more easily treated.”

“These are particularly bad mutations,” says principal investigator Albert de la Chapelle, professor of molecular virology, immunology and medical genetics at Ohio State . “A person who has one of these mutations has an almost 100 percent lifetime risk of cancer.”

The risk is highest for colon cancer, followed by a lower risk of uterine cancer and several other cancers, he says.

“People with Lynch syndrome need closer cancer surveillance, with annual colonoscopies starting at age 25,” de la Chapelle says. “This has been proven to prevent cancer and to prevent death from cancer.”

In addition, he says, it is important for someone in a high-risk family to know that he or she lacks the mutation. “Those relatives do not require the intense cancer surveillance.”

Lynch-syndrome mutations occur in about one person per thousand of the general population.

The study led by de la Chapelle involved 1,066 patients with newly diagnosed colorectal cancer from six hospitals in the Columbus, OH, metropolitan area. Tumor cells from each patient were tested for microsatellite instability (MSI), a hallmark of Lynch syndrome. MSI occurs in more than 90 percent of Lynch syndrome tumors.

To learn the frequency of Lynch syndrome generally, the researchers tested all the tumors for the presence of MSI. They also used an alternative method to prescreen for mutations known as immunohistochemistry. Of the 1,066 tumors tested, 208 showed MSI. Of these, 23 (2.2 percent of the total) had Lynch syndrome mutations. Five of the tumors came from patients that did not meet the usual criteria for diagnosing Lynch syndrome. That diagnosis is largely based on family history and age. Ordinarily, these five cases would have gone undiagnosed.

Furthermore, the 23 people with Lynch syndrome had 117 first-degree relatives who also may have inherited the mutations. The counseling and testing of these individuals revealed 52 people with undiagnosed Lynch syndrome; 65 of the people had no mutations.

“There are now 52 people who know they have Lynch syndrome because they had a relative in this study,” says first author Heather Hampel, a genetic counselor with The James Cancer Hospital and Solove Research Institute.

“It's important that people who have this syndrome know they have it because there is a good chance we can prevent cancer from developing or at least detect it early when it is more easily treated.”

The study also identified immunohistochemistry as an effective way to prescreen colon tumors for MSI, suggesting that Lynch syndrome mutations may be present. The method is less costly than the usual means of identifying MSI, a method known as genotyping, and it can be done by most hospital pathology laboratories. As the next step before proposing nation-wide screening for Lynch syndrome the OSU researchers are planning to implement their screening strategy Ohio-wide.

Testing all colon tumors for MSI is becoming important because patients with tumors that show MSI tend to have a better prognosis than patients whose tumors do not.

“So using this test to prescreen for Lynch syndrome should also help oncologists give patients more accurate information about their prognosis and five-year survival,” Hampel says.
 

- May 5 issue of the New England Journal of Medicine.
 

content.nejm.org/

 
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Other OSU researchers involved in this study were Wendy L. Frankel, Edward Martin, Mark Arnold, Hidewaki Nakagawa, Kaisa Sotamaa, Thomas W. Prior, Judith Westman, Jenny Panescu, Dan Fix, Janet Lockman and Ilene Comeras.

Mount Carmel East Medical Center, Mount Carmel West Medical Center, St. Ann's Hospital, Riverside Methodist Hospital and Grant Medical Center, as well as Ohio State's James Cancer Hospital and Solove Research Institute contributed to this study.

Funding from the National Cancer Institute and the State of Ohio Biomedical Research and Technology Transfer Commission supported this research.


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