TY - JOUR

T1 - Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial

T2 - Planned 10-Year Follow-up

AU - Mathers, John C.

AU - Elliott, Faye

AU - Macrae, Finlay

AU - Mecklin, Jukka Pekka

AU - Möslein, Gabriela

AU - McRonald, Fiona E.

AU - Bertario, Lucio

AU - Evans, D. Gareth

AU - Gerdes, Anne Marie

AU - Ho, Judy W.C.

AU - Lindblom, Annika

AU - Morrison, Patrick J.

AU - Rashbass, Jem

AU - Ramesar, Raj S.

AU - Seppälä, Toni T.

AU - Thomas, Huw J.W.

AU - Sheth, Harsh J.

AU - Pylvänäinen, Kirsi

AU - Reed, Lynn

AU - Borthwick, Gillian M.

AU - Bishop, D. Timothy

AU - Burn, John

AU - the CAPP2 Investigators

N1 - Funding Information: J.C. Mathers reports grants from Medical Research Council and Cancer Research UK and nonfinancial support from National Stach and Bayer during the conduct of the study. F. Macrae reports grants from Cancer Council of Victoria, NSW Cancer Council, SA Cancer Council, and Queensland Cancer Fund, and nonfinancial support from Bayer during the conduct of the study. T.T. Sepp€al€a reports personal fees from Boehringer Ingelheim Finland and Amgen Finland, grants from Jane and Aatos Erkko Foundation, Sigrid Juselius Foundation, Emil Aaltonen Foundation, Relander Foundation, Academy of Finland, Cancer Society Finland, Finnish Medical Foundation, Instrumentarium Science Foundation, and iCAN Precision Medicine Flagship of the Academy of Finland outside the submitted work and is the CEO and co-owner of Healthfund Finland. No disclosures were reported by the other authors. Funding Information: J. Burn, D.T. Bishop, and J.C. Mathers received grants from Cancer Research UK, European Commission, Medical Research Council, and National Institute for Health Research.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1158/1940-6207.CAPR-22-0044

DO - 10.1158/1940-6207.CAPR-22-0044

M3 - Journal article

C2 - 35878732

AN - SCOPUS:85137135872

VL - 15

SP - 623

EP - 634

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 9

ER -