DALLAS, May 16 (UPI) -- Scientists believe they have discovered precisely how a high-fat diet can lead to the development of colon cancer.
Reporting in Friday's issue of the journal Science, researchers at the University of Texas Southwestern Medical Center said the vitamin D receptor, which is found on the surface of cells in the colon and normally binds vitamin D, also binds with and neutralizes a toxic chemical known to cause colon cancer.
David Mangelsdorf, principal investigator of the study and a pharmacologist at UT's Howard Hughes Medical Institute, told United Press International the toxic chemical is called lithocholic acid. It is a type of bile acid released by the body into the small intestine to help break down cholesterol -- a substance that is abundant in high-fat meals.
Most bile acids get recycled back to the liver, but lithocholic acid does not and gets passed to the large intestine and colon. "At high concentrations in the colon, it causes colon cancer," Mangelsdorf said.
In addition to the role lithocholic acid plays in causing colon cancer, researchers also knew people deficient in vitamin D were more likely to develop colon cancer, but how the two were linked was unclear, he said.
Working with human cells, Mangelsdorf's team found that once lithocholic acid binds to the vitamin D receptor, it activates a gene called CYP3A. This in turn triggers release of an enzyme that breaks down the acid and neutralizes its toxicity.
Next the researchers fed vitamin D and lithocholic acid to mice and obtained the same results. They observed the vitamin D receptor played a major role in triggering the chemical cascade neutralizing lithocholic acid.
The way this is related to a high-fat diet is the more fat you eat, the more lithocholic acid the body produces, Mangelsdorf said.
When taken in on a continuous basis, high-fat diets overwhelm the system and eventually more lithocholic acid gets into the colon than can be neutralized. This is what leads to colon cancer, he said.
The researchers believe the finding could lead to the development of a treatment to prevent colon cancer. One way of increasing the production of the enzyme that breaks down lithocholic acid would be to increase vitamin D intake, which also triggers the release of the neutralizing enzyme.
This strategy could be dangerous, however, because high levels of vitamin D can cause hypercalcemia or very high calcium levels in the body, Mangelsdorf said.
An alternative approach is to develop a drug that operates like lithocholic acid or vitamin D and can bind to the receptor and trigger breakdown of the acid. But it should be different enough from vitamin D it does not trigger hypercalcemia, Mangelsdorf said.
He noted two pharmaceutical companies interested in developing such a treatment have already approached him.
Elaine Lanza, principal investigator at the National Cancer Institute, told UPI a preventive drug of that sort may be impractical and unnecessary.
"People need to be on an all-around diet that is not nutritionally deficient and not be overweight and be physically active," she said. All these factors have been shown to lower the risk of colon cancer.
She also pointed out there are other mechanisms causing colon cancer so a drug that only acts on the vitamin D receptor system would not prevent all cases of the disease.
(Reported by UPI Medical and Health Correspondent Steve Mitchell in Washington)
