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Resistant starch appeared to have a protective effect against non-colorectal Lynch syndrome-related cancers, according to long-term follow-up of the randomized CAPP2 trial.

After up to 20 years of follow-up, 5.8% of participants randomized to resistant starch -- a component of dietary fiber found in foods such as bananas, potatoes, grains, pulses, and seeds -- had non-colorectal Lynch syndrome cancers compared with 10.5% of participants randomized to placebo in an intention-to-treat (ITT) analysis (HR 0.54, 95% CI 0.33-0.86, P=0.010), reported John Mathers, PhD, of Newcastle University in Newcastle upon Tyne, England, and colleagues.

This effect was even greater in the per-protocol analysis, which was restricted to participants on treatment for 2 or more years (HR 0.42, 95% CI 0.22-0.81, P=0.0090), they noted in Cancer Prevention Research.

The protective effect of resistant starch against non-colorectal Lynch syndrome cancers was evident in both the ITT (incidence rate ratio [IRR] 0.52, 95% CI 0.32-0.84, P=0.0075) and per-protocol (IRR 0.37, 95% CI 0.19-0.73, P=0.0040) analyses. Effects were particularly pronounced for upper gastrointestinal tract cancers (such as stomach, duodenal, bile duct, and pancreatic cancers), with just five diagnoses in those randomized to resistant starch versus 21 in the placebo group.

Mathers and colleagues called the findings "unexpected," with important implications, "since surveillance for such cancers is challenging and survival after upper GI cancer diagnosis is much lower than for other Lynch syndrome cancers."

Notably, there was no difference between the groups in the incidence of colorectal cancer (CRC; 52 patients on resistant starch vs 53 on placebo).

"Dietary supplementation with resistant starch for this limited time period does not emulate the apparently protective effect of diets rich in dietary fiber against CRC in the general population," Mathers and team observed.

CAPP2 was also designed to investigate the long-term effects of aspirin with resistant starch on cancer incidence in patients with Lynch syndrome, with Mathers and colleagues finding no interaction between aspirin and resistant starch treatments.

An earlier analysis of the trial showed that patients with Lynch syndrome who received aspirin had a compared with those on placebo (HR 0.65, 95% CI 0.43-0.97, P=0.035 in the ITT analysis). Another earlier analysis of CAPP2, based on interim follow-up at a median of 52.7 months, found that on the incidence of CRC in these patients -- findings consistent with those of the current study.

Given that resistant starch does not appear to reduce the risk of CRC in Lynch syndrome patients, what explains the apparent protective effect against other cancers?

"Resistant starch is a type of carbohydrate that isn't digested in your small intestine; instead it ferments in your large intestine, feeding beneficial gut bacteria," said Mathers in a press release. "It acts in effect like dietary fiber in your digestive system. This type of starch has several health benefits and fewer calories than regular starch. We think that resistant starch may reduce cancer development by changing the bacterial metabolism of bile acids and reduce those types of bile acids that can damage our DNA and eventually cause cancer."

"However, this needs further research," he added.

Starting in 1999, the researchers recruited 937 patients with Lynch syndrome (mean age 45). In a 2 × 2 factorial design, participants received 600-mg enteric-coated aspirin or placebo and 30 g of resistant starch or placebo daily. The primary hypothesis of CAPP2 was that each intervention would separately prevent CRC. A secondary outcome was the effect of each intervention on non-CRC cancers.

Participants came from 43 international centers (82% from Europe, and the remainder from Australasia, Africa, and the Americas). The current analysis included 10-year data across all centers, plus up to a further decade of registry follow-up for participants from England, Wales, and Finland.

Mathers and colleagues acknowledged that a potential weakness of the study was that its original hypothesis focused on CRC.

"Detection of an effect on other Lynch syndrome cancers so long after a relatively brief intervention is surprising but not impossible," they wrote. "[M]utagens can damage stem cells and lead to malignancy many years later, especially where DNA repair mechanisms are impaired."

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