[MOL] Life and Death Gene Difference in Colorectal cancer.... [00982] Medicine On Line

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[MOL] Life and Death Gene Difference in Colorectal cancer....

Life and Death Gene Difference in Cancer

One mutation means survival; the other means grimmer outcome

By Edward Edelson
HealthSCOUT Reporter

WEDNESDAY, Jan. 12 (HealthSCOUT) -- Even when a colorectal cancer tumor is deep, the outlook is good if it sprang from a certain kind of genetic corruption, a finding that may lead to ways to tailor treatment.

Two separate mutations can lead to colorectal cancer, and which one a person has can mean a big difference in whether the person survives, Canadian researchers report.

Making the most of that difference could have a huge effect on treating colorectal cancer, which strikes 150,000 Americans a year and is the second leading cause of cancer deaths in North America, the researchers say.

Scientists have known since 1993 that two different genetic abnormalities underlie colorectal cancer, says Dr. Mark Redston, associate scientist at the University of Toronto Samuel Lunenfeld Research Center. He is a member of the group reporting this finding in tomorrow's New England Journal of Medicine.

"What is new in our study is that there is a significant difference in the clinical behavior of these tumors," he says. "The difference in survival holds up against all other known predictors of survival."

One genetic abnormality is for microsatellite instability (MSI). Found in about 17 percent of colorectal cancers, it is many mutations within single genes. The abnormality in the other 83 percent of cases is chromosomal instability (CSI) where there are major mutations in chromosomes, the large molecules that contain many genes.

People with the MSI mutation had a greater chance of surviving, regardless of all other ways of predicting survival, the journal report says. And MSI tumors were much less likely to spread into the deadly cancer colonies that grow in other parts of the body.

The finding comes from genetic studies of 607 patients who were told they had colorectal cancer between 1989 and 1993 in the province of Ontario. The five-year survival rate for patients with the MSI mutation was 76 percent, compared to 54 percent for patients with the CSI mutation. And the incidence of the cancer spreading was less than half for MSI patients.

"What we would like to know now is if we can use this finding to alter treatment," Redston says. "Do some patients require radiation therapy rather than chemotherapy, or vice versa? Hopefully, we can use the information to tailor tumor therapy."

That knowledge could come from major trials that now are under way, he says, by adding genetic information to the other factors governing treatment. "But we will need several years of follow-up to learn about that," he says.

The genetic abnormality in a given case of colorectal cancer is easily detected, Redston says, by studying the genetic material DNA in the tumor sample that doctors routinely take.

DNA testing now helps determine treatment in a number of cancers, including neuroblastoma and some kinds of leukemia, says an accompanying editorial by Dr. Kenneth Offit, chief of the clinical genetic service at Memorial Sloan-Kettering Cancer Center in New York. He agrees that more work is needed to figure out exactly how genetic information can guide treatment.

"Genetic approaches may define subgroups of patients who would benefit from specific chemotherapeutic, immunologic or other investigational therapies," Offit says.

What To Do

This research is in its very early stages, and it may be some time before it has any practical value. Talk to your doctor about being tested for this type of cancer, and if you have this type of cancer, talk to your doctor about the various kinds of treatment.

Warmly, lillian
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