Role Seen for Vitamin A to Prevent Breast Cancer

Experts stress that lab research is preliminary

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HealthDay Reporter

WEDNESDAY, Jan. 5, 2005 (HealthDayNews) -- A glitch in the way the body processes vitamin A may contribute to the development of breast cancer, a new study says.

Although the findings, published in the Jan. 5 issue of the Journal of the National Cancer Institute, are extremely preliminary, researchers hope they may one day translate into a new target for drugs to prevent breast cancer and other malignancies.

Because the findings are so preliminary, they should not be regarded as an invitation to ingest large amounts of vitamin A, experts warn.

"This is very interesting scientific work, but in terms of actual import, people should not be taking extra doses of vitamin A," stressed Dr. Jay Brooks, chief of hematology/oncology at the Ochsner Clinic Foundation in New Orleans.

"It's a distance from taking it from the test tube. . . to humans," added Dr. Julia Smith, director of the Lynne Cohen Breast Cancer Prevention Care Program at New York University Medical Center in New York City. "But I do think that this adds another important piece of information to our knowledge."

Scientists have long suspected that vitamin A may be linked to cancer prevention, but the mechanisms by which this may be happening have not been well understood.

Vitamin A (also known as retinol) is found in various food products, including milk, eggs, and fruits and vegetables, notably carrots. Once taken into the body, vitamin A is stored in the liver and other tissues, including the breast. When needed, it is converted into retinoic acid, which activates the retinoic acid receptor in the cells. This receptor, in turn, regulates the expression of various genes, most of them associated with cell differentiation. When cells differentiate, they turn into cells with specific roles to play. Cells that don't differentiate can turn into tumors.

Previous research had revealed that stores of retinol were low in breast cancer tissue. "The consequence is that even in an individual who has normal vitamin A in the diet, there may be local deficiency in those cells that are premalignant or malignant," said Reuben Lotan, author of an accompanying editorial and deputy division head for research in the division of cancer medicine at the University of Texas M. D. Anderson Cancer Center.

If the cells don't have enough vitamin A stored, the receptor doesn't get activated, the cells don't differentiate, and they can turn cancerous, said study author Eduardo F. Farias, a postdoctoral fellow in medical oncology at Mount Sinai School of Medicine.

Farias and his colleagues set out to discover when cells lost the ability to store vitamin A.

Working with human and mouse breast cells, the researchers discovered the problem was with cellular retinol-binding protein I (CRBP-I), which is involved in the storage process.

"We found that, in the early stages of tumor formation, if you don't have CRBP or LRAT [another protein] to store the retinol, it's likely the receptors will not work in the normal way," Farias said. This means that cells can't differentiate, and therefore start to proliferate into tumors.

The researchers also found that if they put CRBP back into human cells, the tumors didn't progress.

"Cellular storage of retinol is very important to keep the cells under control," Farias explained.

The findings may help in the development of a prognostic marker to help physicians decide which kind of therapy is best. Even further in the future, the findings may hold the key to new drugs.

Gene therapy may also help correct the defect, Lotan said, as may certain drugs already in development that might restore CRBP.

Despite the promise, experts urge caution.

"We have seen so often extremely exciting discoveries that are logical and make sense and that we were hoping to translate into clinical outcomes," said Dr. Stefan Gluck, clinical associate director of the Braman Family Breast Cancer Institute and professor of medicine at the University of Miami School of Medicine. "More often than not we were disappointed, but we were not disappointed all the time. Yes, it's exciting. Yes, we need to take it forward, but don't start taking high levels of vitamin A in the wrong belief that you are doing something good for your body."

Farias added that too much vitamin A is toxic to the body.

More information

For more on vitamin A, visit the Office of Dietary Supplements at the National Institutes of Health.

SOURCES: Eduardo F. Farias, Ph.D., postdoctoral fellow, medical oncology, Mount Sinai School of Medicine, New York City; Reuben Lotan, Ph.D., deputy division head, research, division of cancer medicine, University of Texas M. D. Anderson Cancer Center, Houston; Stefan Gluck, M.D., Ph.D., professor, medicine, division of hematology/oncology, University of Miami School of Medicine, Miami; Julia Smith, M.D., Ph.D., associate director, cancer screening and prevention program, and clinical assistant professor, medicine, New York University School of Medicine, New York City; Jay Brooks, M.D., head, hematology/oncology, Ochsner Clinic Foundation, New Orleans; Jan. 5, 2005, Journal of the National Cancer Institute

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