Scientists Study Biomarkers of High-Fiber Diets to Lower Risk of Colorectal Cancer

NCI CAM Annual Report FY 10

Colorectal cancer (CRC) is the third leading cause of cancer death among both men and women in the United States. Screening for CRC can both reduce the death rate from this disease and prevent it by detecting and removing pre­cancerous growths known as adenomatous pol­yps. Yet despite its demonstrated effectiveness, most Americans over age 50 – the group most at risk for CRC – do not undergo screening.

NCI’s Polyp Prevention Trial (PPT) was a 4-year randomized trial designed to determine the effect of a low-fat, high-fiber diet high in fruit and vegetables on polyp recurrence. Study participants included more than 2,000 people at high risk for CRC because of a history of polyps. Participants were randomly assigned to follow either their usual diet or the diet high in fruits and vegetables. Although the trial results showed no overall difference in adenoma recurrence between the two groups, closer analysis found a substantial decrease in recur­rence among the 25% of participants who most consistently adhered to the diet high in fruits and vegetables*.

For example, the 25% of PPT participants who consumed the largest quantities of beans had a three-fold reduced risk of adenoma recur­rence compared with the 25% of participants who consumed the lowest quantities. Beans, or legumes, are rich in fiber and soluble substances with anti-inflammatory and anticancer ef­fects. And the 25% of PPT participants who consumed the most flavonols – substances abundant in foods such as beans, onions, apples, and tea – had a 76% decreased risk of adenoma recurrence.

Other studies have suggested that insulin resis­tance and low-level chronic inflammation may act together to promote CRC and that a high-fiber diet may influence blood levels of both C-peptide, an established biomarker for insulin resistance, and C-reactive protein (CRP), an established biomarker for inflammation.

Building on these findings, researchers from NCI’s Center for Cancer Research, Pennsylva­nia State University (PSU), and Texas A & M University designed a study to compare the effects of a high-bean diet or a healthy, low-fat control diet on these biomarkers in men at risk for CRC**. Half of the 64 men in the study – known as the Legume Inflammation Feeding Experiment (LIFE) – had a history of polyp removal and half did not***.

“We have learned from the PPT and other stud­ies that not everybody is going to benefit from a particular dietary intervention,” said Nancy H. Colburn, Ph.D., chief of NCI’s Laboratory of Cancer Prevention, who has played a leadership role in both the PPT follow-up studies and the LIFE study, along with Elaine Lanza, Ph.D., who led the PPT while at NCI, and Terryl Hartman, Ph.D., of PSU. “But we have also learned that subgroups of people can benefit.”

The men in LIFE were randomly assigned to spend 4 weeks on one of the two study diets, followed by a 3-week break, followed by 4 weeks on the other study diet. The diets were designed to maintain the men’s existing weight. Blood concentrations of CRP declined by 20% while the men were on the high-bean diet and by about 18% while they were on the control diet. A trend was seen toward reduced blood concentrations of C-peptide on the high-bean diet. In preliminary results using a novel method that isolates RNA from patients’ fecal stools, researchers identified sets of gene expres­sion changes after 4 weeks on the high-bean diet that may predict a reduced risk for polyp recurrence.

Meanwhile, further analyses of the PPT have identified two potential biomarkers for adenoma recurrence. PPT participants with elevated blood levels of homocysteine – an amino acid that can promote inflammation, tissue damage, cardiovascular disease, and cancer – had a two-fold increased risk of adenoma recurrence. And the greatest reduction in risk for recurrence of high-risk and advanced adenomas (those most likely to become cancerous) was seen in participants who consumed the most flavonols and had decreased blood concentrations of IL-6, a substance that promotes inflammation and may promote growth of colorectal tumors.

Dr. Colburn noted that the goal of the post-PPT studies “is to personalize dietary interventions to prevent CRC by matching them with the groups of people most likely to benefit. To achieve that goal, we need biomarkers that accurately identify those most likely to benefit from an intervention and that can be measured noninvasively by means of a simple blood or stool test.”