Author: John C. Mathers, Faye Elliott, Finlay Macrae, et al. (on behalf of the CAPP2 researchers)
Source: Cancer Prevention Research | Research Article
ABSTRACT
Background: The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS).
Methods: Volunteers with LS were randomly assigned in a double-blind study to receive either 30g of resistant starch (RS) per day or a placebo for up to 4 years. We present long-term cancer outcomes based on a 10-year follow-up plan from recruitment, supplemented by data from National Cancer Registries for up to 20 years in England, Wales, and Finland.
Results: A total of 463 participants received RS and 455 received the placebo. After up to 20 years of follow-up, there was no difference in the incidence of colorectal cancer (n = 52 cases diagnosed in the RS group compared to n = 53 cases in the placebo group).
However, the number of participants with non-colorectal Lynch syndrome cancers was significantly lower in the RS group (n = 27) compared to the placebo group (n = 48). Intention-to-treat (ITT) analysis showed a hazard ratio (HR) of 0.54 (95% CI, 0.33-0.86; P = 0.01). Per-protocol analysis showed an HR of 0.42 (95% CI, 0.22-0.81; P = 0.009). The protective effect was particularly pronounced for upper gastrointestinal cancers (n = 5 in the RS group compared to n = 21 in the placebo group). The risk reduction for non-colorectal cancers was evident during the first 10 years after randomization and continued through the following decade.
Conclusion: Daily intake of 30g of RS for an average of 2 years significantly reduces the incidence of non-colorectal cancers in patients with Lynch syndrome.
INTRODUCTION
Lynch syndrome (LS) is an autosomal dominant genetic condition caused by pathogenic variants in mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, or PMS2. Individuals with this syndrome have a high risk of developing colorectal cancer (CRC) and a range of extra-colorectal cancers, including endometrial, ovarian, stomach, small intestine, bile duct, gallbladder, pancreatic, upper urinary tract, brain, and skin cancers.
Resistant starch (RS) is any type of starch that is not absorbed in the small intestine. RS travels to the colon, where it is fermented by resident bacteria, producing short-chain fatty acids (SCFAs), primarily acetate, propionate, and especially butyrate. Butyrate has diverse impacts on cell biology, including regulating apoptosis, cell differentiation, and growth, while possessing distinct anti-cancer properties.
MATERIALS AND METHODS
Trial design: CAPP2 is an international, multicenter trial with a 2x2 factorial design. Participants were randomly assigned to receive:
- 600 mg of aspirin or a corresponding placebo.
- 30 g of resistant starch (supplied as Novelose 240 and 330) or a placebo (Amioca cornstarch) per day.
RS dosage: The 30g daily dose was chosen because it is equivalent to the consumption levels of populations with low colorectal cancer rates and is approximately 10 times the average consumption in western countries.
RESULTS
Impact on extra-colorectal cancers: This is the most significant finding of this study. During a mean follow-up period of 10 years (and up to 20 years through registries), the group using resistant starch had a much lower incidence of Lynch syndrome-related cancers (excluding colorectal):
- Placebo group: 48 individuals developed cancer.
- RS group: 27 individuals developed cancer.
- Risk reduction rate: 46% (ITT) and 58% (per-protocol).
Upper gastrointestinal cancers: The data showed the most substantial reduction in the risk of upper gastrointestinal tumors (stomach, duodenum, bile duct, pancreas):
- The placebo group recorded 21 cases.
- The RS group recorded only 5 case
Impact on colorectal cancer: In contrast to aspirin (which was proven in the same trial to reduce colorectal cancer after 5 years), resistant starch did not show a significant reduction in colorectal cancer during this follow-up timeframe.
DISCUSSION
Our results indicate that the chemopreventive effect of resistant starch on extra-colorectal cancers is substantial and sustainable.
The mechanism may involve altering the fermentation process in the large intestine, leading to changes in the concentration of secondary bile acids or other metabolites that travel through the bloodstream, affecting distant organs. Another hypothesis is that changes in the gut microbiota may influence inflammatory responses or the body's overall immune system, thereby preventing tumor formation in other organs associated with Lynch syndrome.
RESEARCH TEAM CONCLUSION
Supplementing resistant starch into the diet is a feasible, low-cost, and safe strategy to reduce the burden of extra-colorectal cancers-types of cancer that are inherently difficult to screen via endoscopy-in patients at high genetic risk.
Notes for research team members:
- The document emphasizes that the effects of RS appear "late" (2-4 years after the end of the intervention phase).
- The dose of 30g RS/day is considered the optimal dose for clinical prevention purposes in this study.
Source: According to Professor J.C. Mathers and colleagues at:
https://aacrjournals.org/cancerpreventionresearch/article/15/9/623/707714/Cancer-Prevention-with-Resistant-Starch-in-Lynch
