Vitamin D Receptor Gene Linked to Reduced Prostate Cancer Risk in Study at NIEHS And UNC

Men with a particular vitamin D receptor gene appear to have only a third the risk of developing a prostate cancer requiring surgery, scientists at the National Institute of Environmental Health Sciences and the University of North Carolina at Chapel Hill have found.

Their study of 200 men, published in the journal Cancer Research, is the latest tantalizing suggestion of a possible role for vitamin D -- and/or the body's inherited ability to make use of the vitamin -- in reducing prostate cancer risk. This cancer is the second leading cancer killer of men. More than 40,000 men are expected to die of the disease this year.

"Different men have different risks of prostate cancer," NIEHS' Jack A. Taylor, M.D., Ph.D., said, "and this could be based in part on how their bodies utilize Vitamin D."

Two copies of the vitamin D receptor gene, which helps control how vitamin D is used by the body's cells, are inherited, one from each parent. The gene comes in either of two forms designated by researchers as either T or t, so that each person ends up with one of three two-gene combinations, TT, Tt, or tt.

The study found that men having the tt combination seem to enjoy one-third less likelihood of developing prostate cancer requiring surgery. Does the tt combination provide for better use of vitamin D? "We can't say for sure yet, but we'll be pursuing an answer," Dr. Taylor said.

The T and t genes were studied in blood samples from 108 prostate surgery patients and 170 male non-cancer patients at nearby hospitals of the University of North Carolina, Chapel Hill, N.C., and Duke University, Durham, N.C. Eight percent of the prostate surgery patients had tt genotype, whereas about twenty percent of the controls did.

Vitamin D is unusual in that it can be absorbed from dietary sources and also synthesized by the body in response to sunlight .

There have been studies suggesting that men with low vitamin D levels have a higher risk of prostate cancer and that the further north a man lives (presumably with less sunlight exposure, on average) the higher his risk as well.

Other studies have shown that vitamin D metabolites can suppress prostate cancer cells cultured in a laboratory, while a rodent study has suggested that vitamin D analogs (similar chemicals) may have a protective effect.

"But the body's metabolism of vitamin D is complex," Dr. Taylor said, "and simply increasing vitamin D consumption or sunlight exposure may not affect levels of the active form in the blood." Vitamin D exerts its effect in the body by binding to the cell's vitamin D receptor. The vitamin D receptor gene helps direct the activity.

Dr. Taylor said, "Together with the other studies, our findings support the idea that vitamin D plays an important role in prostate cancer andthat different men may have different risks. It also suggests some new ideas for thinking about prostate cancer prevention."

"We are very excited about the use of this information in attacking prostate cancer," Dr. Taylor continued, "but we are definitely not recommending that men take additional vitamin D based on the results of this study."

NIEHS is one of the National Institutes of Health, most of which are in Bethesda, Md., but NIEHS is located in central North Carolina. Dr. Taylor is in the Epidemiology Branch of the Environmental Diseases and Medicine Program at NIEHS.

In 1995, other NIEHS researchers, in collaboration with scientists from Johns Hopkins University, identified and cloned a gene that suppresses the spread of prostate cancer. Like many other cancers, prostate cancer may result from interactions between a genetic susceptibility and environmental factors, such as smoking, diet and exposures to chemicals and radiation.

Working with Taylor were Ari Hirvonen (now working in Finland), Mary Watson, of NIEHS, Gary Pittman of UNC and Douglas A. Bell of NIEHS. Collaborating to provide blood samples for testing was James L. Mohler, UNC.