Disappearance of enzyme linked to prostate cancer

November 22, 1994|By Jonathan Bor | Jonathan Bor,Sun Staff Writer

Researchers at the Johns Hopkins Oncology Center have identified a genetic change occurring during a man's lifetime that appears to trigger prostate cancer by knocking out a cell's ability to resist cancer-causing chemicals in the environment.

Although further research is needed to determine the discovery's full significance, scientists yesterday said the finding may provide an important step toward understanding what causes the most frequently diagnosed cancer among American men.

The scientists noticed the genetic change while studying 91 human prostate cancers -- tissues obtained from autopsies and biopsies of men who suffered from the disease. The defect was found in all of the samples analyzed.

Dr. William G. Nelson, assistant professor of oncology and urology, said the alteration shuts down a cell's ability to manufacture an enzyme that is a part of the body's natural cancer-fighting mechanism. Without the enzyme, the cell is more likely to turn cancerous and spawn a larger tumor.

"If continued research confirms this hypothesis, tests for the enzyme could serve as an early diagnostic marker for prostate cancer," Dr. Nelson said. Many physicians believe that early detection is crucial to treating cancer successfully.

Details of the finding were reported in yesterday's edition of Proceedings of the National Academy of Sciences.

Each year, 200,000 new cases of prostate are diagnosed and 38,000 men die of the disease, making it the second leading cause of cancer death among men.

Dr. Nelson said the genetic alteration occurs during a person's lifetime when a piece of DNA -- the genetic blueprint within each cell -- undergoes a chemical change. The change is not passed from generation to generation.

Scientists could find no trace of the cancer-fighting enzyme, known as glutathione S-transferase, in 88 of the 91 human prostate cancers they studied. The enzyme is part of a much broader family of cancer-fighting chemicals produced by the body.

Two years ago, unrelated research by Dr. Paul Talalay of the Johns Hopkins School of Medicine revealed that cruciferous vegetables -- a family that includes broccoli, cauliflower and brussels sprouts -- stimulate the body's production of these enzymes.

Dr. Talalay, a molecular pharmacologist, speculated that people eating diets rich in these vegetables might be able to fend off several types of cancer, including prostate, breast and colon.

If true, this may explain why American men have much higher death rates from prostate cancer than do Japanese men, who tend to eat more vegetables and fewer high-fat foods. When Japanese men migrate to the United States, they become more vulnerable to prostate cancer as they adopt the U.S. cuisine.

Yesterday, Dr. Nelson speculated further, saying that the cruciferous vegetables might lower a person's odds of developing prostate cancer even in the face of the genetic alteration. While the genetic change knocks out one cancer-fighting enzyme, he said, the vegetables appear to increase production of related enzymes that play a similar role.

"This enzyme is one of a large family of enzymes," he said. "It may be that by making a ton of the other enzymes, you may be able to compensate."

While this genetic alteration is not hereditary, Hopkins scientists studying patterns of prostate cancer believe that about 10 percent of prostate cancers are passed from generation to generation. The inherited cases appear to be caused by a different mechanism.

Scientists suspect that some cases are inherited because they have observed families in which an alarming number of men develop the disease.

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