Role of cancer mutation scrutinized.

A genetic mutation thought to predispose some people to colorectal cancer may have a more enigmatic link to the disease than originally suspected.

The mutation seems to prevent the APC gene from encoding a protein that acts as a natural tumor suppressor in the body. Researchers reported recently that the mutation, called 11307K, is found in 6 percent of Ashkenazi Jews but that more than 10 percent of Jewish colorectal cancer patients they studied carry the mutation (SN: 8/30/97, p. 133).

More recent genetic tests, of 264 Ashkenazi Jews from 158 families with a history of breast or ovarian cancer--but not colorectal cancer--uncovered the mutation in 12 people, researchers at the Fox Chase Cancer Center in Philadelphia report in the Dec. 15, 1997 Cancer Research. This 7 percent mutation rate is close to the 6 percent figure found in the earlier study; however, none of the 12 carriers had ever had colorectal cancer--nor had any of their relatives.

This research raises questions about the mutation's link to colorectal cancer, but it doesn't necessarily refute the earlier findings. It approached the puzzle from a different angle--whether people carrying the mutation have a family history of the disease--and it focused on a group with different cancer histories, says coauthor Andrew K. Godwin of Fox Chase.

The more recent study may have found no colorectal cancer because people at risk of the other cancers didn't live long enough to get it, Godwin says. Or the mutation may only work in concert with some other factor, he says.

"We need to look at [members of random] families in the Ashkenazi population who live long enough--and see who has the mutation, who gets colon cancer, and who doesn't," says Bert Vogelstein of Johns Hopkins Medical Institutions in Balti more, a coauthor of the earlier study.