A placebo-controlled clinical trial in people with high hereditary risk of a wide range of cancers has shown a major preventive effect from resistant starch, found in a wide range of foods such as oats, breakfast cereal, cooked and cooled pasta or rice, peas and beans and slightly green bananas.

The study, funded by Cancer Research UK, the European Commission, Medical Research Council and the National Institute for Health Research and known as CAPP2, involved almost 1,000 (n = 918) patients from around the world diagnosed with Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), an inherited disorder that increases the risk of many types of cancer, particularly colorectal cancer and a broader spectrum of cancers, especially endometrial cancer. Lynch syndrome arises from germline mutations in mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or also EPCAM, deletions within which result in aberrant expression of MSH2.

The population prevalence of Lynch syndrome is between 1 in 125 and 1 in 400 people.

Ongoing study
In 2011, the authors of the study reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomized trial of daily acetylsalicylic acid (aspirin; Bayer) versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population.[1]

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The study results revealed that a regular dose of resistant starch, also known as fermentable fibre, taken for an average of two years, did not affect cancers in the bowel but did reduce cancers in other parts of the body by more than half. The observed effect was particularly pronounced for upper gastrointestinal cancers including esophageal, gastric, biliary tract, pancreatic and duodenum cancers.[1]

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The astonishing effect was seen to last for 10 years after participants stoped taking the supplement.

The study, led by experts at the Universities of Newcastle and Leeds, published in Cancer Prevention Research, a journal of the American Association for Cancer Research (AACR), is a planned double blind 10 year follow–up, supplemented with comprehensive national cancer registry data for up to 20 years in 369 of the participants.[1]

Professor Sir John Burn, FRCP FRCPE FRCOG FRCPCH FMedSci, a professor of Clinical Genetics at Newcastle University and Newcastle Hospitals NHS Foundation Trust.

Outcome
In their article, the authors present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland.

A total of 918 patients participated in the study (n = 463 participants received 30 g resistant starch (RS) daily and n = 455 participants received placebo for up to 4 years).[1]

The researchers observed that after up to 20 years of follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to resistant starch against n = 53 on placebo) but fewer participants had non-colorectal Lynch syndrome cancers in those randomized to resistant starch (n = 27) compared with placebo (n = 48); the intention-to-treat (ITT) analysis [HR, 0.54; 95% confidence interval (CI), 0.33–0.86; P= 0.010]. The intention-to-treat analysis allowed for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of resistant starch against non–colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32–0.84; P = 0.0075).

Role of aspirin
Previous research published as part of the same trial, revealed that aspirin reduced cancer of the large bowel by 50%.[2]

“We found that resistant starch reduces a range of cancers by over 60%. The effect was most obvious in the upper part of the gut,” explained Professor John Mathers, BSc, Dip. RNutr, PhD, FAfN, professor of Human Nutrition at Newcastle University.

“This is important as cancers of the upper GI tract are difficult to diagnose and often are not caught early on,” he said.

“Resistant starch can be taken as a powder supplement and is found naturally in peas, beans, oats and other starchy foods.  The dose used in the trial is equivalent to eating a daily banana; before they become too ripe and soft, the starch in bananas resists breakdown and reaches the bowel where it can change the type of bacteria that live there,” Mathers added who is also editor in chief of the British Journal of Nutrition.

“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 – it acts in effect, like dietary fibre 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 to reduce those types of bile acids that can damage our DNA and eventually cause cancer. However, this needs further research,” Mathers noted.

Reducing risk
“When we started the studies over 20 years ago, we thought that people with a genetic predisposition to colon cancer could help us to test whether we could reduce the risk of cancer with either aspirin or resistant starch,” explained Professor Sir John Burn, FRCP FRCPE FRCOG FRCPCH FMedSci, a professor of Clinical Genetics at Newcastle University and Newcastle Hospitals NHS Foundation Trust ran the trial with Professor Mathers.

“Patients with Lynch syndrome are high risk as they are more likely to develop cancers so finding that aspirin can reduce the risk of large bowel cancers and resistant starch other cancers by half is vitally important,” he added.

“Based on our trial, the United Kingdom’s National Institute for Health and Care Excellence (NICE) now recommend Aspirin for people at high genetic risk of cancer, the benefits are clear – aspirin and resistant starch work,” Burns said.

Long term study
Between 1999 and 2005, nearly 1000 participants began either taking resistant starch in a powder form every day for two years or aspirin or a placebo.

At the end of the treatment stage, there was no overall difference between those who had taken resistant starch or aspirin and those who had not. However, the research team anticipated a longer-term effect and designed the study for further follow-up.

In the period of follow-up, there were just 5 new cases of upper GI cancers among the 463 participants who had taken the resistant starch compared with 21 among the 455 who were on the placebo.

The team are now leading the international trial, CaPP3, with more than 1,800 people with Lynch syndrome enrolled to look at whether smaller, safer doses of aspirin can be used to help reduce the cancer risk.

More about Lynch syndrome
The Onco’Zine Brief: Lynch Syndrome and Genetic Testing (May 24, 2022)

Clinical trials
A randomised controlled trial of colorectal polyp and cancer prevention using aspirin and resistant starch in carriers of hereditary nonpolyposis colorectal cancer – ISRCTN59521990
Lynch syndrome research registry pilot study – ISRCTN14826039
Finding the Best Dose of Aspirin to Prevent Lynch Syndrome Cancers (CaPP3 Israel) –NCT02497820

Reference
[1] Mathers JC, Elliott F, Macrae F, Mecklin JP, Möslein G, McRonald FE, Bertario L, Evans DG, Gerdes AM, Ho JWC, Lindblom A, Morrison PJ, Rashbass J, Ramesar RS, Seppälä TT, Thomas HJW, Sheth HJ, Pylvänäinen K, Reed L, Borthwick GM, Bishop DT, Burn J. Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up. Cancer Prev Res (Phila). 2022 Jul 25:OF1-OF12. doi: 10.1158/1940-6207.CAPR-22-0044. Epub ahead of print. PMID: 35878732.
[2] Burn J, Sheth H, Elliott F, Reed L, Macrae F, Mecklin JP, Möslein G, McRonald FE, Bertario L, Evans DG, Gerdes AM, Ho JWC, Lindblom A, Morrison PJ, Rashbass J, Ramesar R, Seppälä T, Thomas HJW, Pylvänäinen K, Borthwick GM, Mathers JC, Bishop DT; CAPP2 Investigators. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Lancet. 2020 Jun 13;395(10240):1855-1863. doi: 10.1016/S0140-6736(20)30366-4. PMID: 32534647; PMCID: PMC7294238.

Featured image: Professor John Mathers, BSc, Dip. RNutr, PhD, FAfN, professor of Human Nutrition at Newcastle University. Photo courtesy: © 2017 – 2022 Newcastle University. Used with permission.

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