Vitamin A and Cancer

A recent study published in the Journal of the National Cancer Institute suggests that certain women may be lacking a protein that helps vitamin A bind to cells.

Dr. Rafael Mira-y-Lopez of Mount Sinai Medical Center in New York and colleagues contend that about a quarter of all women who have breast cancer are lacking a protein called CRBP, which may not only inhibit their ability to absorb vitamin A but may also hold a clue to the development of cancer.

The researchers took tissue samples from 15 healthy women who had breast reductions and compared them to tissue samples taken from 49 breast cancer patients. They found CRBP in all of the normal tissue samples from the breast reductions as well as in 33 of 35 specimens of normal tissue found next to cancer tissue. However, in the cancerous tissues, 12 showed no sign of CRBP.

The researchers could only speculate on the role that vitamin A and CRBP might play in cancer cell proliferation. "CRBP assists the body when it converts a form of vitamin A-retinal-into its acidic form, which in turn helps cells develop into their specialized roles," said the authors. But when CRBP is absent, they suggested, vitamin A is not converted and cell "programming" goes haywire, resulting in cancerous cells.

In a related editorial, Dr. Ethan Dmitrovsky of Dartmouth Medical School in Hanover, New Hampshire, emphasized the importance of the findings by Mira-y-Lopez' team. "This [CRBP] alteration may account for some of the abnormal growth properties found in some breast cancers," Dmitrovsky wrote. "Future work [in this area] may lead to strategies which correct this particular defect."

Touting Vitamin A

Another study published in the Journal of the National Cancer Institute found that a gene believed to suppress the growth of breast cancer tumors appears to be switched off in the early stages of the disease. But a two-pronged treatment that includes a form of vitamin A (called retinol) may help to reactivate this tumor-suppressing gene and thus prevent tumor growth.

Dr. Martin Widschwendter from the University of Innsbruck, Austria and colleagues identified a gene called RAR-beta-2 that is believed to stop the growth of several types of tumors, including breast cancer tumors. But when this gene is inexplicably turned off, the tumors appear to grow unencumbered.

The Austrian researchers found that a substance identical to vitamin A (a retinol-like substance called ATRA), when mixed with a demethylating agent, can turn RAR-beta-2 back on. In theory, this would then have a suppressing effect on the growth of cancerous tumors.

However, while their studies on laboratory animals have shown promise, they acknowledge that ATRA is still far too toxic for use in humans. Nonetheless, the researchers suggest that retinol-like substances such as ATRA have significant potential for preventing and eliminating breast and other cancers.

Mixed Results

A third study published in the Journal of the National Cancer Institute came to two different conclusions. Dr. Umberto Veronesi from the Istuto Nazionale Tumori in Milan and colleagues found that another substance that is molecularly similar to vitamin A, fenretinide, has no significant effect in preventing a second breast tumor from occurring in postmenopausal women with breast cancer. (In fact, it may actually increase the risk.) However, fenretinide in premenopausal women appeared to lower their risk of a second breast cancer.

"We have been in certain ways surprised because we didn't expect such a difference in the sense that this drug is very active in very young women," said Veronesi. But after menopause, he noted, "it appears to exert the opposite effect." In fact, his team's findings suggest that postmenopausal women had a slightly greater risk of a second breast cancer when fenretinide was taken.

Too Much of a Good Thing

The National Academy of Sciences Institute of Medicine has just issued recommendations for how much vitamin A is safe to take-no more than 10,000 international units (IU), or 3,000 micrograms per day.

Yet many vitamin A nutritional supplements sold in retail outlets or over the Internet contain up to 25,000 IU. Too much of the vitamin can lead to liver and nerve damage, bone and joint pain, bone loss and birth defects.

The bottom line is that there is simply no substitute for a healthy, well-balanced diet that includes plenty of fruits and vegetables-both of which are chock full of vitamin A.

SOURCES:
Journal of the National Cancer Institute, March 15, 2000; 15:92(6):475-480
Journal of the National Cancer Institute, May 17, 2000; 92:780-781, 826-832
Journal of the National Cancer Institute, November 3, 1999; 91:1847-1856

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