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Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up

Lookup NU author(s): Professor John Mathers, Dr Anne-Marie Gerdes, Dr Harsh Sheth, Lynn ReedORCiD, Dr Gillian Borthwick, Professor Sir John BurnORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


©2022 The Authors; Published by the American Association for Cancer Research. ABSTRACT: The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g resistant starch (RS) daily or placebo for up to 4 years. We 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. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53 on placebo) but fewer participants had non-colorectal LS cancers in those randomized to RS (n = 27) compared with placebo (n = 48); intention-to-treat (ITT) analysis [HR, 0.54; 95% confidence interval (CI), 0.33-0.86; P = 0.010]. In ITT analysis, allowing for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of RS against non-colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32-0.84; P = 0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-colorectal cancer LS cancers was detectable in the first 10 years and continued in the next decade. For colorectal cancer, ITT analysis showed no effect of RS on colorectal cancer risk (HR, 0.92; 95% CI, 0.62-1.34; P = 0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30 g daily RS appears to have a substantial protective effect against non-colorectal cancer cancers for patients with LS. PREVENTION RELEVANCE: Regular bowel screening and aspirin reduce colorectal cancer among patients with LS but extracolonic cancers are difficult to detect and manage. This study suggests that RS reduces morbidity associated with extracolonic cancers. See related Spotlight, p. 557.

Publication metadata

Author(s): Mathers JC, Elliott F, Macrae F, Mecklin J-P, Moslein G, McRonald FE, Bertario L, Evans DG, Gerdes A-M, Ho JWC, Lindblom A, Morrison PJ, Rashbass J, Ramesar RS, Seppala TT, Thomas HJW, Sheth HJ, Pylvanainen K, Reed L, Borthwick GM, Bishop DT, Burn J

Publication type: Article

Publication status: Published

Journal: Cancer Prevention Research

Year: 2022

Volume: 15

Issue: 9

Pages: 623-634

Online publication date: 01/09/2022

Acceptance date: 01/07/2022

Date deposited: 20/09/2022

ISSN (print): 1940-6207

ISSN (electronic): 1940-6215

Publisher: American Association for Cancer Research


DOI: 10.1158/1940-6207.CAPR-22-0044

PubMed id: 35878732


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Funder referenceFunder name
Cancer Research UK
European Commission