Multimarker molecular stool test for colon cancer unaffected by medication, lifestyle factors

Research on an investigational DNA methylation test for colorectal cancer demonstrated that the only clinical variable that influenced test results was age, according to results presented at the AACR Annual Meeting 2012, held here March 31 - April 4.

"There was a progressive increase in background methylation levels that varied widely between methylation markers tested as a patient aged," said David Ahlquist, M.D., professor of medicine and a consultant in gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. "For example, median background methylation levels of the TFPI2 gene increased 49 percent in patients from age 50 to age 80, whereas levels for the BMP3 gene increased by only 0.2 percent across this age range."

His group at the Mayo Clinic, in collaboration with Exact Sciences, developed the multimarker molecular stool test, which is highly sensitive to the critical cancer screening targets of early-stage cancers and precancerous adenomas, he said.

"This test, if broadly applied, should have a very important impact on reducing both the mortality and incidence of colorectal cancer," Ahlquist said.

The researchers examined common patient variables, including age, sex, race, alcohol consumption, tobacco use, body mass and medication use in 500 patients undergoing screening colonoscopy or polyp follow-up. Patients had a normal colonoscopy in the last three years.

With the exception of age, none of the variables influenced test results, nor did family history of colorectal cancer or polyps or personal history of polyps. These results mean that "patients don't have to change their lifestyle to have this test," Ahlquist said. "That was important from a patient-friendly standpoint for a test like this and could benefit compliance."

Researchers have selected the two markers least affected by age for further test development and validation based on these study results.

"If we can minimize the false positives, that will reduce the cost of the whole screening program by avoiding unnecessary colonoscopies," Ahlquist said.

The screening test is currently undergoing FDA validation in a multicenter study in the United States and Canada, which is expected to be completed in the fall. The Mayo Clinic and Ahlquist have a financial interest in the technology referenced in this announcement.