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Gene Test Finds Colon Cancer Patients at High Risk

Analysis indicates likelihood of recurrence

THURSDAY, Jan. 17, 2002 (HealthDayNews) -- A sophisticated genetic analysis of cancer cells appears to identify patients with cancer of the colon and rectum who could most benefit from aggressive treatment, researchers report.

A painstaking measurement of the differences in chromosomes, the cellular bodies that contain the genes, identified patterns associated with the likelihood that colorectal cancer would recur after surgery, researchers at the Johns Hopkins University School of Medicine and Emory University report in the Jan. 19 issue of The Lancet.

It is a finding important for the 135,000 Americans diagnosed with colorectal cancer each year. Most recover after surgery, but the cancer recurs in up to 30 percent of cases. The prognosis for those patients is not good, even when they are given chemotherapy; the disease causes 55,000 deaths annually.

Several research teams have been looking at genetic markers that could tell whether the cancer is likely to recur. Their attention has been focused mostly on chromosomes 8 and 18, two of the 23 pairs in each human cell, which are known to carry genes associated with colorectal cancer.

The new study used a techniques called digital single-nucleotide polymorphism (SNP), developed by Wei Zhou, assistant professor of hematology and oncology at the Emory University Winship Cancer Institute, and Bert Vogelstein of Johns Hopkins.

The idea is to determine whether a cancer cell has lost the normal balance of chromosomes. "With each cell division in a lot of tumor cells, the chromosome content changes," Zhou explains. "Cells might have more or less copies of a chromosome than is normal."

The digital SNP study of cells from 180 patients divided them into three groups. One group had the normal balance for both chromosome 8 and 18 -- two chromosomes, one inherited from the father, one from the mother. The second group had imbalances of only one of the chromosomes, and the third group had imbalances of both chromosomes. All the patients in the first group were alive after five years. The five-year survival rate for patients with one chromosomal imbalance was 74 percent. For patients with two imbalances, it was 58 percent.

This is not the first study to give such results, Zhou acknowledges. "Several studies have indicated that the loss of two chromosomes might be associated with the worst prognosis," he says. "Our study is different."

The difference is that the new study is more precise at singling out cancer cells that might be surrounded by normal cells and counting their chromosomal differences carefully, Zhou says. "Even with 50 percent normal tissue, we can predict whether the cells have allelic [genetic] imbalances," he says.

The new study has "confirmed and solidified previous work" along the same lines, says Dr. Garth Anderson, professor of cellular and molecular biology at the Roswell Park Cancer Institute and co-author of an accompanying editorial in journal.

"It is a larger study than done before and demonstrates that it is valuable to do this," he says. "The concept is that if you identify tumors that are more likely to occur, you can use more aggressive treatment. It makes sense to sort people out by differences at the genome level."

But advances in the treatment of colorectal cancer are needed to make the concept work, Anderson says. "It would be nice if we had better drugs for adjuvant therapy," he says. "Hopefully,, in the future something better will come along."

As it is, the results need verification in a larger study of patients newly diagnosed with colorectal cancer, Zhou says. If the method is proved to work, it could be done with equipment that is available in most medical centers, he says.

What to Do: For information on colorectal cancer, consult the American Cancer Society or the National Cancer Institute.

SOURCES: Interviews with Wei Zhou, Ph.D., assistant professor of hematology and oncology, Emory University Winship Cancer Institute, Atlanta; Garth Anderson, M.D., professor of cellular and molecular biology, Roswell Park Cancer Institute, Buffalo, N.Y.; Jan. 19, 2002, The Lancet
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