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Uterine cancer may be clue to inherited syndrome

07.08.2006
A new study suggests that women with endometrial cancer should be screened for inherited mutations that could lead to a high risk of several other cancers.

The study showed that 1.8 percent, or about one in 50, of newly diagnosed endometrial cancer patients have mutations for Lynch syndrome, an inherited condition also known as hereditary nonpolyposis colon cancer, or HNPCC.

People with Lynch syndrome mutations are at high risk for colon, endometrial, ovarian and gastric cancer. Endometrial, or uterine, cancer is the most common cancer in women with this condition.

The study, led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), is published in the Aug. 1 issue of Cancer Research.

The study is the first to comprehensively screen a large number of women with uterine cancer for Lynch syndrome mutations, said Heather Hampel, a genetic counselor in the clinical cancer genetics program and first author of the study.

“It's important to identify women with one of these mutations because they have a very high risk for developing colon cancer, and they may not be aware of that risk,” said Hampel. “Because this is hereditary, half of her siblings and children may also be at risk for the syndrome.

“For this reason, the relatives of a person with Lynch syndrome should also be screened for the responsible gene mutation,” said Hampel, a clinical assistant professor in the department of internal medicine.

Family members who also have the mutation need close monitoring for early cancer detection, including an annual colonoscopy starting at age 25 and endometrial cancer screening (using ultrasounds and biopsies) starting at age 30, Hampel said.

Family members without the mutation can follow the American Cancer Society's guidelines for colorectal cancer screening, which call for a colonoscopy every 10 years starting at age 50 and no routine endometrial cancer screening, she said.

This study involving 543 women was led by Albert de la Chapelle, co-leader of the OSUCCC Molecular Biology and Cancer Genetics Program. Participants in the study were diagnosed and treated for endometrial cancer at the three major hospital systems in Columbus, Ohio, between 1999 and 2003.

To learn the frequency of Lynch syndrome mutations among all newly diagnosed endometrial cancer patients, the researchers tested tissue from the tumors from each patient for MSI (microsatellite instability), a change in the DNA of tumor cells that occurs in more than 90 percent of Lynch syndrome tumors. Of the 543 tumors tested, 118 showed MSI. Because these patients are more likely to have Lynch syndrome, they participated in the gene testing portion of the study and nine (1.8 percent) were found to have Lynch syndrome mutations.

In addition, the researchers used another technique called immunohistochemistry, to prescreen the tumors for mutations. Follow-up gene testing performed on patients with abnormal immunohistochemistry results showed that one additional woman with an MSI-negative tumor also had a Lynch syndrome mutation.

Of the 10 Lynch syndrome patients, seven did not meet the usual criteria for diagnosing the hereditary condition. That diagnosis is largely based on family history and age. Ordinarily, these seven cases would have gone undiagnosed.

In addition, the counseling and testing of 21 relatives of the 10 women with Lynch syndrome revealed 10 additional people with Lynch syndrome mutations.

The study is the continuation of an Ohio State colon cancer study also led by de la Chapelle that was published in the New England Journal of Medicine in 2005. In that study, 2.2 percent of newly diagnosed colon cancer patients tested positive for Lynch syndrome.

That study recommended testing all newly diagnosed colon cancer patients for the inherited syndrome, Hampel said. As a result, Ohio State University Medical Center now routinely screens all newly diagnosed colon cancer patients to find those most likely to have Lynch syndrome using the immunohistochemistry test, Hampel said. She hopes for a similar change in the standard of care for endometrial cancer patients as well.

“We think such genetic testing should be nationwide on all colon cancer and endometrial cancer patients, but further cost-benefit analysis and study is needed first,” Hampel said. “Screening for Lynch syndrome can save lives.”

In addition to Ohio State's James Cancer Hospital and Solove Research Institute, hospitals in the Mount Carmel Health System and OhioHealth, all in Columbus, contributed to the study.

Funding from the National Cancer Institute and the Andrew McGriffin Barford Memorial Fund supported this research.

Eileen Scahill | EurekAlert!
Further information:
http://www.osumc.edu

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