NEWS RELEASE, 10/25/99

UC Berkeley scientists report first indication that a genetic mutation can protect against acute leukemia

By Kathleen Scalise, Public Affairs

BERKELEY-- Scientists at the University of California, Berkeley, report the first discovery of a genetic mutation that can protect against some types of acute leukemia. Their findings appear in this week's issue of the journal, "Proceedings of the National Academy of Sciences."

The researchers found that adults who carry double copies of a particular mutated gene in the folate pathway were "very significantly" protected from the life-threatening disease, said project leader Martyn Smith, a UC Berkeley professor of public health.

"It looks like the folate pathway is very important in this kind of cancer," Smith said.

The mutated gene codes for an enzyme called 5,10-methylenetetrahydrofolate reductase or MTHFR. It controls how the body processes folate. Folate, or folic acid, is one chemical in the vitamin B complex commonly found in green vegetables, fresh fruit, liver and yeast, and that is included in many vitamin supplements.

Individuals with two mutated copies of the MTHFR gene were five times less likely to develop acute lymphocytic leukemia as compared to the 85 percent of the U.S. population that produces only a "normal" enzyme, Smith and his colleagues found.

The mutated enzyme appears to work by shifting the way folate is used in the body, said UC Berkeley graduate student Christine Skibola. In the end, more of the chemical is channeled toward DNA synthesis instead of being used to methylate other biological compounds with which folate interacts.

"Our work suggests that having sufficient folate going toward DNA synthesis is key in preventing this kind of leukemia," said Skibola, who works with the Smith group in public health.

The new findings may mean a diet fix is the route to prevention. Skibola said it may be important to increase recommended rates of folate consumption significantly.

"Very likely we can't change the genetics of what's going on with our enzymes," Smith concurred. "But we might be able to change our environment to reduce the incidence of the disease. We could, for instance, get more folate in our food. Fast food - your burgers and your fries and what not - are generally very low in folate. Fresh fruit juice and green vegetables have much more."

Leukemia is cancer of the bone marrow. There are about 28,000 adult cases of leukemia annually in the United States and 5,000 cases in children. Generally, the cause is unknown and the disease is often fatal.

"We can't explain the majority of these cases as there is no family link," said Smith. "However we have shown that by studying genetics we may get clues to the environmental cause, in this case lack of folate, which allows us to intervene and prevent the disease. This is the goal of public health work."

Other co-authors of the paper include Eleanor Kane, Eve Roman and Raymond Cartwright of the Leed's Leukaemia Research Fund Centre for Clinical Epidemiology in the United Kingdom; and Sara Rollinson and Gareth Morgan of the Department of Haematology at the University of Leeds.

The work was funded by the National Foundation for Cancer Research. The researchers are part of UC Berkeley's Health Sciences Initiative, a research effort that draws scientists from both the physical and biological sciences into a multidisciplinary search for the solutions to today's major health problems.


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