Deficiency of natural protein associated with brain cancer Substance defends against nitrosamines, Wash. study finds

July 09, 1996|By SEATTLE TIMES

SEATTLE -- Having too low a level of a naturally occurring protein in the body is strongly associated with the development of brain cancer, University of Washington scientists have found.

The protein, called MGMT, defends brain cells against damage caused by nitrosamines, a cancer-causing chemical found in preserved foods, tobacco smoke and fermented products such as beer. The research found that patients with low levels of the protein were more likely to develop brain tumors than others in the study.

Although the research does not have any immediate application, it adds to knowledge about the ways brain cancers occur and increases understanding of how to prevent the disease through avoiding nitrosamines.

In the study, researchers found that they were 4.6 times more likely not to find MGMT in patients with malignant brain tumors than in other brain-surgery patients.

The research "is very important in helping us understand the genesis of brain tumors," said John Silber, UW research assistant professor of neurological surgery and director of the study. The research is being reported in today's edition of the Proceedings of the National Academy of Sciences.

About 18,000 new brain tumors -- most of them malignant -- are detected annually in the United States. Even with treatment, few of these patients live beyond two years after diagnosis.

Silber said most people are protected against nitrosamines' effects by MGMT (O6-methylguanine-DNA methyltransferase). But a relatively small portion of the population apparently has a genetic defect that results in little or no production of the protein, which seems to have a primary purpose of protecting against the damage.

Nitrosamines damage DNA, which makes up genes.

This can lead to uncontrolled growth, or cancer, in glial cells, one of the two major cell types in the brain.

"This will at least give us an idea of what lifestyle changes are important," said Silber, including avoiding nitrosamines.

In the UW study, the researchers analyzed noncancerous tissue removed near the brain tumors of 117 patients. The patients underwent surgery for these primary brain cancer tumors -- tumors that originated in the brain rather than spreading from another cancer site. The tissue was compared with that of 43 other patients who had had brain surgery for other reasons, mainly to control epileptic seizures.

Fifty-five percent (64 of 117 cases) of the brain-tumor patients had undetectable levels of MGMT, compared with 12 percent (five of 43 patients) of the other patients.

The likelihood of undetectable MGMT was much higher in older brain-tumor patients. About 75 percent of those older than 50 had the low levels, compared with 22 percent of those younger than 19.

Brain tumors normally take a long time to develop. Thus, the older a person is, the higher the risk of a tumor. If the person has little protective MGMT, it increases the risk.

"The level of MGMT appears to be the only mechanism identified thus far that accounts for the increasing incidence of brain tumor with age," said Mitchel Berger, professor of neurosurgery and a co-researcher in the study.

Still, young people do develop brain cancer. Ten percent of all cases occur among children younger than 15.

Pub Date: 7/09/96

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