New screening test for colon cancer spots cancer genes

Thursday, January 31st 2002, 12:00 am
By: News On 6

BOSTON (AP) _ A new screening test can find colon cancer in its early, curable stage by detecting extremely small traces of cancer genes in patients' stool.

The experimental test, still several years away from routine use, offers an entirely new approach to mass screening for colon cancer, which will kill an estimated 48,000 Americans this year.

Doctors believe the test has the potential to be much more accurate than the current stool test, which checks for blood. That test can also detect the disease early, but it misses some cancers, and the ones it finds are outnumbered by false alarms.

The new test looks for a gene that is usually faulty in the earliest stage of colon cancer. It finds the gene inside cancer cells that are sloughed off into the stool.

The test in its current form accurately found the bad gene in 57 percent of people with early cancer or precancerous growths, but it gave no mistakenly positive results in people who were cancer-free. Researchers say that with fine-tuning, they can make the test 70 percent accurate and still avoid alarming false readings.

``All of these cancers are in theory curable if detected,'' said Dr. Bert Vogelstein. ``If we could detect 70 percent with a simple gene-based test, that would save a lot of lives, and that's what we're shooting for.''

Vogelstein and colleagues developed the test at the Johns Hopkins Kimmel Cancer Center in Baltimore. They described it in Thursday's issue of the New England Journal of Medicine.

``Can you get out of going for a colonoscopy by having this? Not yet. But that is the hope, potentially. It's promising as far as it goes,'' said Dr. Barbara Conley, chief of the diagnostics research branch at the National Cancer Institute.

The new test represents a practical payoff of the revolution in understanding how cancer happens. Scientists now know that cancer begins with genetic mutations that make cells lose their normal control over growth, and they understand in precise detail many of the genes and defects involved.

While much attention has been on using this insight to find better treatments, Vogelstein said more precise screening methods are also an important result, since ``historically the best way to control cancer is through early detection and prevention.''

Colon cancer arises when four or five genes become mutated. In more than 90 percent of cases, the first to go bad is one called APC. APC is known as a cancer suppressor gene, since its usual duty is overseeing other genes that regulate the normal cycle of cells' growth and death.

Developing a test to look for the bad gene involved solving two technological challenges: finding the APC gene itself in human stool and then sorting out the bad copies from the normal ones.

Only one in 1 billion strands of DNA in stool comes from the person. The rest are bacterial. And APC is just one of the 35,000 or so genes inside every human cell. Furthermore, even if someone has cancer, as few as one in 250 copies of the APC genes in their stool is bad, since stool also contains many more normal genes from non-cancerous cells.

In testing on 74 people, the researchers found an average of four copies of the APC gene in every milligram of stool among those with cancer and two copies among those with precancerous growths. The test then examined the genes to see if they worked properly.

That the researchers ``found APC genes in all 74 stool samples they studied is a tour de force,'' journal editor Robert S. Schwartz said in an accompanying commentary. But because it missed nearly half the cancers, ``we see it as a step in the arduous journey toward a reliable, noninvasive molecular screening test.''

Dr. Durado Brooks, colon cancer director at the National Cancer Society, called the research ``highly encouraging.'' Besides increasing the accuracy, he said, the researchers will have to prove the test can find cancer in a broad range of people, not just in those whose cancer status is already known.

Vogelstein said further testing is under way, and a more accurate and practical version should be available within three to five years. The research was financed by several government and private agencies.