Dietary Flavonols Tested for Colorectal Cancer Prevention

Center for Cancer Research

The NCI Polyp Prevention Trial (PPT) was a multicenter, randomized clinical trial, with almost 2,000 individuals, that tested whether a diet (high-fiber, low-fat, and high in fruits and vegetables) could prevent the recurrence of precancerous adenomas (polyps) in the colon and rectum. However, the researchers found no preventive effect of the healthy diet on polyp recurrence, even after long-term follow up.

Gerd Bobe, Ph.D., a research fellow in NCI’s Laboratory of Cancer Prevention, decided to take a closer look at the data from the PPT, focusing on the study participants’ intake of flavonols. Flavonols are bioactive compounds in plant-derived foods found in high concentrations in beans, onions, apples, and tea.

“Two recent case-control studies* had shown a protective effect of flavonols against colorectal cancer, and another analysis, specifically of fruit and vegetable intake of the PPT participants, had shown that food groups rich in flavonols were more protective,” said Dr. Bobe.

He and his NCI colleagues discovered that a high intake of flavonols by some PPT participants was associated with a significantly decreased risk of advanced adenoma recurrence compared with study participants who had a very low intake of the compounds.

At NCI**, Dr. Bobe is currently testing several individual flavonol compounds for colorectal cancer prevention in a two-stage mouse model of carcinogenesis. The mice are first exposed to a known carcinogen, azoxymethane, and then a colon irritant, dextran sodium sulfate, to specifically initiate tumors in the gastrointestinal tract. Then, they are given different flavonol compounds to test the effects.

These experiments will go beyond identifying the most effective flavonols and the best dosage levels for preventing the formation of colorectal tumors in the mice. Dr. Bobe and his colleagues also hope to identify the molecular targets for the most promising flavonols. The researcher team will also attempt to determine if there are any reliable biomarkers in the blood that can indicate whether a flavonol compound is hitting the molecular target and suppressing tumor formation in the mice.

Dr. Bobe and his colleagues have already demonstrated in previous studies*** the effectiveness of navy beans as colon cancer preventives. They were able to show that cooked navy beans and their residue or extracts reduced the formation of colon lesions in obese mice exposed to azoxymethane. They found that the navy bean diet altered a panel of genes associated with inflammation and identified two proteins that could potentially serve as biomarkers of the diet’s anti-carcinogenic effect.

After performing similar experiments with flavonols in their two-step mouse model of colorectal tumor formation, “we’re going to go back to analyze the data from the PPT,” explained Dr. Bobe. “We have serum samples stored from the trial and detailed dietary data, and we’ll look to see whether we can relate the dietary data to levels of the serum biomarkers we identify in our animal studies.”

He and Nancy Colburn, Ph.D., director of the NCI Laboratory of Cancer Prevention, hope to eventually conduct a short-term feeding study in about 30 or 40 human volunteers, who would receive a flavonol supplement for four weeks and would be monitored for inflammation by changes in biomarkers. This planned experiment will depend upon preclinical data that validates biomarkers for flavonols’ ability to hit their putative molecular targets successfully.