They warned that taking huge doses of the vitamin would do more harm than good, causing the body to pull calcium out of the bones, but said drugs might be designed to mimic the effects of the vitamin.
And, they added, the best way to prevent colon cancer is to eat less fat.
Colon cancer is the second biggest cancer killer in the United States and other industrialized countries, after lung cancer. It is strongly linked to a diet heavy in red meat and animal fat, as well as to smoking and heavy alcohol use.
"Our findings suggest a new look at the relationship between nutrition and cancer, particularly how vitamin D protects against colon cancer," David Mangelsdorf, a professor of pharmacology and a researcher at the Howard Hughes Medical Institute at the University of Texas Southwestern in Dallas, said in a statement.
"The rate of colorectal cancer is much higher in the United States -- where a high-fat diet is common -- than in Japan, where people don't eat a lot of fat and colorectal cancer is almost nonexistent. But no one has understood why that is."
Writing in the journal Science, Mangelsdorf and colleagues said they found at least part of the answer lies in lithocholic acid, a bile acid produced to help digest fat.
"Lithocholic acid is probably the most toxic compound that your body naturally makes, so you have to have a way to get rid of it," Mangelsdorf said in a telephone interview.
"Normally, bile acids are made in the liver and stored in the gallbladder. Bile acids solubilize foods. When you eat a high-fat diet, your body makes more bile acids."
Usually they are efficiently recycled, with the exception of lithocholic acid, Mangelsdorf said.
"It does a variety of bad things. One of those bad things is induce changes in DNA. If you give animals high concentrations, just directly put it into the intestine, they get colon cancer."
But laboratory animals given doses of vitamin D and then given lithocholic acid do not get colon cancer, he said.
Colon cancer patients also have high concentrations of lithocholic acid, Mangelsdorf said.
Vitamin D is necessary for the body to absorb calcium -- that is why milk is fortified with it -- but this finding explains its role in colon cancer.
"The surprise from this study is that the vitamin D receptor, which we normally think of as mediating calcium, also has another role, which is to detoxify lithocholic acid," Mangelsdorf said.
Vitamin D is also toxic in large amounts, so people at risk of colon cancer cannot take large amounts and hope to prevent it. Too much causes the body to over-absorb calcium, even pulling it from the bones, which causes a range of problems.
"The goal is to come up with a compound that does not have those hypercalcemic effects but still has protective effects," Mangelsdorf said. "You might be able to develop a drug that protects against colon cancer."
In the meantime, there is, of course, an easier solution, Mangelsdorf advises. "The most important thing you can do to extend life is to get less fat in your diet," he said.
He said humans evolved to be able to handle a little fat, but nothing like the overwhelming flood of calories that Americans -- and to a lesser degree people in rich countries the world over -- inflict on their bodies.
"The problem is the system gets overwhelmed," he said.