Two new studies have added further support to the idea that genetic mutations found in stool can be used to identify people with colorectal cancer. A screening test based on these mutations could replace the current method of screening stool for trace amounts of blood, said Bernard Levin, M.D., of the University of Texas M. D. Anderson Cancer Center, and a co-author on both studies.
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Two days later, the team reported in the Lancet that a different mutation, in the BAT 26 gene, could be detected specifically in people with proximal colorectal cancers.
Levin said that these two markers may someday be combined into a highly specific test to identify people who need further evaluation with colonoscopy.
Warning Signs
Colorectal cancer is the second leading cause of cancer in the United States. Although a colonoscopy may be used to identify and remove cancers or precancerous polyps, the procedure is invasive and carries some risk.
Doctors often first perform a fecal occult blood test. This test may warn of cancer by detecting traces of blood in the stool. While the fecal occult blood test is the most commonly performed screening test for colorectal cancer in the United States, the test is limited in its ability to distinguish the cancer from benign conditions. Likewise, the lack of blood does not rule out cancer because tumors bleed intermittently.
A more specific indicator of colorectal cancer may be DNA mutations, which come directly from the tumor. Last June, Vogelstein and his coworkers reported in the Journal of the National Cancer Institute that they could detect colorectal cancers by screening stool for three different gene mutations: TP53, K-RAS, and BAT 26 (See News, June 6, 2001, p. 802). A series of mutations in these genes leads to colorectal cancer.
The first mutation in this series of events occurs in a gene called APC. Detecting APC mutations in stool could help identify people with the earliest, most treatable forms of cancer. However, until now, finding for the APC mutation in stool has been a challenge.
In one of the two new studies, Vogelstein and his coworkers reported that using a new technique, they could identify APC mutations in 26 of 46 people with relatively early colorectal cancers; there were no false positives.
In the second study, Vogelstein and his coworkers screened 134 stool samples for the BAT 26 mutation and correctly identified 17 out of 18 patients with BAT 26 mutations in their proximal tumors. Like the APC test, the BAT 26 test yielded no false positives.
Proximal tumors have been especially difficult to detect because they are the farthest from the anus. A sigmoidoscopy, which is less invasive than the colonoscopy, can identify only distal colorectal cancers. Levin said the BAT 26 test could be coupled with sigmoidoscopy to help identify people who need colonoscopies.
More Work
Wendy Atkin, Ph.D., deputy director of the Colorectal Cancer Unit at St. Marks Hospital in the United Kingdom, said these results are "exciting news" but cautioned that the specificity needs to be confirmed with larger sample sizes. "None of these papers have had adequate numbers of people known to be normal," she said.
A large-scale randomized screening study funded by the National Cancer Institute is ongoing to compare the sensitivity and specificity of the stool DNA test and the stool blood test in 4,000 people.
Levin said that the real challenge now is to integrate the markers into a working test. He anticipates that the technology will become available to the public in 3 to 5 years. But, he cautioned, "for the general public, its important to emphasize that they shouldnt be waiting for the results of these or other tests to be screened."
Levin added that he is optimistic that these tests will be effective. "I think we have new technologies that are evolving that are going to make searches for specific proteins or genes more efficient," he said. "I think were going to see an upturn in the pace of these investigations."
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