Uterine Cancer May be Clue to Inherited Syndrome

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.