Unequal Gene Activity Linked To Colon Cancer

Researchers have discovered that a subtle difference in the activity of a pair of genes may be responsible for one of every 10 colon-cancer cases.

The work, led by researchers with the Human Cancer Genetics Program at Ohio State University’s Comprehensive Cancer Center, is the first to link this particular gene conclusively as a cause of colon cancer, and it may provide clinicians with a new way to identify people who are at high risk for the disease.

The study was published online today at AAAS Science Express Web site and will appear in the journal Science in coming weeks.

The gene, transforming growth factor beta receptor 1 (TGFBR1), normally helps protect against cancer. Everyone inherits two copies of this gene and they both produce equal amounts of the RNA that is needed for making the TGFBR1 protein. But in some people, one of these two genes produces less of this than the other.

“The fact that we saw this abnormal difference in gene expression in at least 10 percent of the colon-cancer patients and in very few people without colon cancer strongly suggests that it plays an important role in this disease,” said principal investigator Albert de la Chapelle, a researcher with the human cancer genetics program.

“Moreover, if this difference is found in patients with colon cancer, it should prompt a study of other family members who, as determined by genetic counseling, are likely to have also inherited the trait,” he said.

The study’s findings must be verified in a larger number of patients, de la Chapelle added, but they indicate that this difference in gene expression appears to increase a person’s risk of colon cancer nearly nine times.

“It is possible that testing for this abnormal expression may become part of clinical practice when evaluating a patient’s colon-cancer risk,” he said.

Inherited gene changes have been implicated in about 5 percent of colon-cancer cases, but 20 to 30 percent of people diagnosed with it have a family history of the disease, suggesting that genes may play a much greater role.

This research may explain many more cases of colon cancer.

For this study, de la Chapelle and his colleagues analyzed white blood cells from 138 colon-cancer patients who had gene markers that allowed the researchers to distinguish one TGFBR1 gene from the other. In 29 of these cases, one of the two genes was at least one-third less active than the other, a level of difference that other experiments showed impairs the protein’s normal function in cells.

The researchers also tested 105 non colon-cancer patients as controls, only three of whom showed a one-third difference in expression between the two genes.

“We and others must now determine the molecular cause of the difference so that we can begin to design ways to correct it and perhaps eliminate the elevated risk of cancer,” said de la Chapelle.

Funding from the National Cancer Institute, the Walter S. Mander Foundation, the Jeannik M. Littlefield-AACR Grant in Metastatic Colon Cancer Research, and the Fundación Ramón Areces supported this research.

Source: Newswise