TUESDAY, Sept. 26, 2006 (HealthDay News) -- Scientists have devised more precise ways to identify individuals who might have gene mutations associated with Lynch syndrome, the most common hereditary form of colorectal cancer.
These tools could guide patients and physicians when considering actual testing, treatment and even prevention options.
"We're asking the question, 'Who should get genetic testing?' These tests are trying to better predict, so we can focus testing and resources," said Dr. Jerald D. Wishner, director of colon and rectal surgery at Northern Westchester Hospital Center in Mount Kisco, N.Y. "The significance of a positive genetic test is very real in the clinical world in terms of treatment options."
Added Dr. Jeffrey Weitzel, director of clinical cancer genetics at City of Hope Comprehensive Cancer Center in Duarte, Calif., "Can we develop tools that are more accurate to help us predict who may or may not be a carrier? That would be an adjunct to decisions about testing."
Reports on the new tests were published in the Sept. 27 issue of the Journal of the American Medical Association.
Lynch syndrome is the most common form of hereditary colorectal cancer in the West, accounting for 2 percent to 5 percent of all cases of the disease. The condition is mainly associated with mutations in the MLH1 and MSH2 genes, and people with these mutations also often have a higher risk of other cancers, including ovarian, stomach, small bowel and brain tumors.
Although genetic screening for the mutations is available, it is not foolproof and is expensive.
"It's about a $3,000 test," Wishner said. "Insurance companies don't always pay for it."
Other criteria for determining who might be prone to Lynch syndrome also have significant limitations.
The first model, PREMM1,2 (Prediction of Mutations in MLH1 and MSH2), incorporates personal and family history variables.
"In a more quantitative way, this tells people what their risk is of having the syndrome," said Dr. Sapna Syngal, senior author of the study and director of the familial GI (gastrointestinal) cancer program at Dana-Farber/Brigham and Women's Cancer Center in Boston.
People can use the model themselves online. "We're hoping that it's an easier way to figure out people's risk," Syngal said. "The criteria that existed before was very complicated, and it was hard to know if you were high-risk or not."
The second study, MMRpro, was developed by researchers at Johns Hopkins University. MMRpro estimates probability based on family history of colorectal and endometrial cancer.
"This is a model that predicts the Lynch syndrome better than what we already had," said Sining Chen, lead author of the study and assistant professor of environmental health sciences and biostatistics at Johns Hopkins Bloomberg School of Public Health. "This is a tool that helps identify people who are at high risk. It's ready to go. You can download software off of the Web page."
While representing progress, both methods need improvement, experts said.
For one thing, both are cumbersome. "The MMRpro requires collecting so much data," Wishner said. "There's more potential for inaccuracies. Clearly, more research needs to be done."
"Almost certainly, there will be a number of people who will go out and use these in clinical practice," Weitzel added. "None of these models is going to make me not do the test. I don't want to miss the true positives. At the end of the day, the most important thing is going to be clinical judgment."
More information
For more on Lynch syndrome, visit the U.S. National Institutes of Health.
