From Our 2007 Archives

Study Sheds Light on Genetics of Colorectal Cancer

By Ed Edelson
HealthDay Reporter

WEDNESDAY, Feb. 14 (HealthDay News) -- Events both inside and outside a gene can affect the risk of developing a kind of colorectal cancer, Australian researchers are suggesting in a new report.

Mutations of the gene, designated MLH1, which is involved with cellular repair, are known to increase the risk of developing a tumor called hereditary nonpolyposis colorectal cancer, which accounts for about one case in 50 of colorectal cancers. But the risk can also be increased by addition of a methyl group -- consisting of one carbon atom and three hydrogen atoms -- to the gene.

Researchers at several centers in Sydney reported that the "methylation" of the gene was transmitted from several mothers to their children. In one case, it was then erased from the son's sperm, but it persisted in three other children.

"These findings demonstrate a novel pattern of inheritance of cancer susceptibility," the researchers wrote in the Feb. 15 issue of the New England Journal of Medicine.

"The idea is that there is some plasticity to the genetics" of cancer, said Dr. Andrew Feinberg, professor of medicine at Johns Hopkins University School of Medicine, who wrote an accompanying editorial in the journal. "There could be genetic sequences that could predispose to cancer, and the methylation on top of it could also have an effect. A genetic sequence could increase the chance of becoming methylated."

Heather Hampel, a genetics counselor at Ohio State University, who has long experience with the subject, said the study showed that methylation of a gene could be passed from generation to generation. That has not been clearly established, however, she said, so children of mothers with the methylated gene would have to be screened for it.

"We have assumed that methylation is acquired with age and can't be passed on to children," Hampel said. "But these sons clearly had the gene methylated in their whole bodies when they were born."

The methylation did disappear from one of the sons. But the fact that it could be inherited "is telling us that there may be more hereditary cases (of cancer) we don't know about," Hampel said.

The study shows that women can pass on the methylated version of the gene, but it isn't clear whether men can, too, she said, making for a "complicated inheritance pattern."

"The exciting part of it is that it shows this may be more common than we have appreciated in the past," Hampel said.

And the genetic picture might be more complicated than the study indicates, Feinberg said. "There are data showing that there might be incomplete activation of the gene and that the erasure might not be entirely complete," he said.

SOURCES: Andrew Feinberg, M.D., professor of medicine, Johns Hopkins University School of Medicine, Baltimore; Heather Hampel, genetics counselor, Ohio State University, Columbus; Feb. 15, 2007, New England Journal of Medicine

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