• 5/13/2001
  • Janet McConnaughey
  • AP

A simple genetic test can help doctors accurately predict whether people with common white patches inside their mouths are likely to develop deadly oral cancer.

The technique developed at the University of Oslo could help physicians assess patients with the patches, called oral leukoplakia, so they can be treated early if cancer appears likely. “I think there is a message to physicians: Beware of white patches,” said Dr. Jon Sudbo, whose study was published in Thursday’s issue of the New England Journal of Medicine. “There is a message to consumers and patients: Beware of white patches. And get them investigated.”

The key is the number of chromosomes in the cells that make up those patches. If it’s the normal 46, cancer is unlikely. If the number is doubled, cancer is more likely. And it becomes very likely if the number cannot be divided evenly by 23, the number of chromosomes received from each parent.

More than 300,000 people around the world, including about 30,000 in the United States, are diagnosed each year with oral cancer, making it the nation’s No. 11 cancer and the ninth most common worldwide. More than half of those people die within five years, largely because the cancers are hard to diagnose early. The death rate hasn’t changed in more than 20 years.

Because there is no way to know which white patches will develop into cancer, doctors often remove them as a precaution. But there is also no good way to tell whether they have removed enough. Sudbo and his colleagues kept a long watch, averaging 8 1/2 years, on 150 patients with white patches where cells showed abnormal formation and organization, a further indication that cancer might develop. Out of 103 patients with leukoplakia made up of cells with 46 chromosomes, only three developed cancer. Twelve of 20 patients with 92-chromosome patches developed cancer. But cancer developed in 21 of the 27 patients with “aneuploid” lesions, those in which the chromosomes did not divide evenly by 23. Two of the six non-cancerous patients started with 46-chromosome lesions which later turned aneuploid.

“This gives us the opportunity to treat these patients with chemopreventive agents, which much likely has a much better effect than waiting until it becomes cancer,” Sudbo said. No drugs have yet been proved to prevent oral cancer, but many are being tested, said Dr. Scott Lippman, chairman of clinical cancer prevention at the M.D. Anderson Cancer Center in Houston. He said Sudbo’s study was very compelling, but no single test can find every likely cancer because so many different changes can turn cells to cancer.

Thirty to 50 percent of all oral cancers have the normal 46 chromosomes. The test is unlikely to predict those cancers, said Lippman and Dawn Willis, scientific program director for the American Cancer Society. However, they said, several other studies published within the past year have found other genetic markers for oral cancer. For instance, there’s also a risk of cancer if cells from the white patches have lost one gene from any of a number of specific pairs. The risk increases with the number of such missing genes. Many mouth cancers could be prevented by avoiding tobacco and alcohol, she said.

Further studies should develop guidelines for analyzing the results for several different markers at once, Lippman said. “That’s much more predictive than any one marker.” Other studies could also give doctors a much better idea of how far outside the edges of the white patches they need to go to cut out all pre-cancerous cells, he said. Genetic tests will let doctors check on whether they got all changed cells, without a biopsy.