New Clues to Detecting a Killer

By Christine Gorman

When Ronald Reagan's doctors announced two years ago that the President suffered from colon cancer, the world also learned that his brother Neil had received the same diagnosis. That apparently incidental detail did not surprise cancer researchers. They have long known that family members can share a genetic predisposition to the disease, but the exact mechanism was a mystery. Last week scientists in Britain and Israel reported in the journal Nature that they had discovered that there is a faulty gene that triggers a rare form of colon cancer and found its general location. The discovery, said Sir Walter Bodmer, director of research at London's Imperial Cancer Research Fund and a principal investigator, may eventually enable doctors to provide better diagnosis and treatment for all patients with colon cancer, which in the West is the second most deadly form of the disease, after lung cancer.

Bodmer's team studied 13 families with familial adenomatous polyposis (FAP), a rare hereditary condition affecting adolescents in which the large intestine is carpeted with hundreds of small growths called polyps, which frequently become cancerous. After reading about a boy who suffered from several disorders, including FAP, that seemed linked to a missing portion of chromosome No. 5,* the researchers hypothesized that all FAP victims lack the same genetic material. They were right. Afflicted patients had the chromosome defects; healthy ones did not. The scientists further postulated that a person with FAP inherits from one parent a healthy gene that deters polyp growth and from the other a faulty gene. Over time even the healthy gene becomes inactive, allowing tumors to form.

Yet FAP accounts for less than 1% of the 170,000 new cases of colorectal cancerdiagnosed in the U.S. and Britain each year. That led Bodmer to ask, "Could the same gene be involved in the normal run of colon cancers?" The researchers analyzed tumors removed from 45 patients with common colorectal cancer. Result: the section of chromosome 5 that contains the FAP gene was missing in more than 25% of the cases. The finding suggested that such cancers occur only after one protective gene is lost and the other is inactivated. Says Gastroenterologist Sidney Winawer, of the Memorial Sloan-Kettering Cancer Center in New York City: "This gives us a better idea of where to look for a genetic cause of colon cancer."

Should researchers pinpoint that genetic defect, the next step will be to develop a simple diagnostic test. Doctors now recommend that everyone over 50 periodically undergo routine, if unpleasant, examinations with a proctosigmoidoscope, a hollow, lighted tube that is inserted in the colon to look for signs of cancer. A blood test that could alert people that they carried a greater risk of developing colorectal cancer might motivate them to seek frequent checkups.

"Obviously the hope must be that as we learn how the gene works, we can use that to find new ways of treatment," says Bodmer. Indeed, researchers speculate that some remedies may be fairly simple: a diet high in fiber and calcium, for example, may prevent or compensate for these genetic deficiencies.

FOOTNOTE: *Pairs of human chromosomes are assigned a number based on their size and other characteristics.

With reporting by Helen Gibson/London