New Test Reveals Advance in Colorectal Cancer Detection Study Shows Novel Genetic Marker

A new colorectal cancer-screening test may detect benign and malignant colorectal tumors earlier than other methods currently available.

A study published in the Jan. 31 issue of the New England Journal of Medicine reports that the test reveals changes in the APC gene, a gene associated with colorectal cancer. Until now, no technology existed to identify these abnormalities in stool samples at the molecular level.

Principal investigator for the study is Dr. Bert Vogelstein of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and the Howard Hughes Medical Institute. Dr. Vogelstein teamed with Dr. Bernard Levin, vice president for cancer prevention at The University of Texas M.D. Anderson Cancer Center; Dr. Stanley R. Hamilton, M.D. Anderson’s division head of pathology and laboratory medicine; and others in discovery of this noninvasive screening test. The National Cancer Institute, the National Colorectal Cancer Research Alliance and a philanthropic gift from Caroline Wiess Law funded the study.

"This is the first time we’ve identified protein markers derived from abnormal APC gene changes in stool samples," Dr. Levin said. "With this new technology, we now can detect genetic changes associated with the earliest colorectal lesions. Colorectal cancer is the nation’s second leading cancer killer, second only to lung cancer, but is about 90 percent curable when detected early."

Expected to be available to the public in three to five years, the test should be one of the simplest colorectal cancer screening tools in existence, Dr. Levin said.

Further research among people with and without colorectal tumors is needed to validate the findings. In the future, only individuals who test positive for APC genetic changes and other gene markers under study will be recommended for colonoscopy, a more extensive and invasive procedure.

"Gene-based tests of this type should allow us to avoid unnecessary colonoscopies, one of the procedures currently recommended for colorectal cancer screening," Dr. Levin said.

The new test detects colorectal cancer at the earliest stages by identifying changes in the APC gene from a single stool sample, with no dietary changes required in the days before the test, report researchers. Unlike this new test, the existing fecal occult blood test requires three consecutive stool samples with dietary restrictions for several days before testing begins.

The APC gene is a tumor suppressor gene – a type of gene that helps prevent cells from becoming cancerous. When tumor suppressor genes malfunction, cancer cells may develop.

Researchers report that the APC gene acts as a cancer gatekeeper in the gastrointestinal tract by preventing buildup of molecules associated with cancer, called catenins. If the APC gene’s function is disturbed, catenin accumulation can occur, which may lead to cancer. The new test reveals changes in the APC gene that indicate the gene is acting as a faulty gatekeeper, allowing catenin buildup. The APC gene malfunctions in an estimated 80 percent of early colorectal cancers.

Meanwhile, current colorectal screening recommendations remain in place, Dr. Levin said.

Beginning at age 50, all adults should begin colorectal cancer screening. Screening recommendations include annual fecal occult blood tests; a flexible sigmoidoscopy every five years; annual fecal occult blood testing combined with a flexible sigmoidoscopy (the most preferred of these three options); double contrast barium enemas every five years; and a colonoscopy every 10 years. Colonoscopies may begin earlier and/or be done more frequently if an individual is at increased risk.

American Cancer Society figures estimate that 148,300 individuals will be diagnosed with colorectal cancer in the United States this year, and about 56,600 individuals are expected to die of the disease.

In 1998, Medicare began providing coverage for colorectal screening. Individuals 50 or older should ask their doctor about colorectal cancer screening.

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©2006 Texas Medical Center

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