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Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial

Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial
Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial
BACKGROUND: Observational studies report that higher intake of dietary fibre (a heterogeneous mix including non-starch polysaccharides and resistant starches) is associated with reduced risk of colorectal cancer, but no randomised trials with prevention of colorectal cancer as a primary endpoint have been done. We assessed the effect of resistant starch on the incidence of colorectal cancer.

METHODS: In the CAPP2 study, individuals with Lynch syndrome were randomly assigned in a two-by-two factorial design to receive 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was done with a block size of 16. Post-intervention, patients entered into double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint for this analysis was development of colorectal cancer in participants randomly assigned to resistant starch or resistant-starch placebo with both intention-to-treat and per-protocol analyses. This study is registered, ISRCTN 59521990.

FINDINGS: 463 patients were randomly assigned to receive resistant starch and 455 to receive resistant-starch placebo. At a median follow-up 52·7 months (IQR 28·9-78·4), 53 participants developed 61 primary colorectal cancers (27 of 463 participants randomly assigned to resistant starch, 26 of 455 participants assigned to resistant-starch placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 1·40 (95% CI 0·78-2·56; p=0·26) and Poisson regression accounting for multiple primary events gave an incidence rate ratio (IRR) of 1·15 (95% CI 0·66-2·00; p=0·61). For those completing 2 years of intervention, per-protocol analysis yielded a HR of 1·09 (0·55-2·19, p=0·80) and an IRR of 0·98 (0·51-1·88, p=0·95). No information on adverse events was gathered during post-intervention follow-up.

INTERPRETATION: Resistant starch had no detectable effect on cancer development in carriers of hereditary colorectal cancer. Dietary supplementation with resistant starch does not emulate the apparently protective effect of diets rich in dietary fibre against colorectal cancer.

FUNDING: European Union, Cancer Research UK, Bayer Corporation, National Starch and Chemical Co, UK Medical Research Council, Newcastle Hospitals Trustees, Cancer Council of Victoria Australia, THRIPP South Africa, The Finnish Cancer Foundation, SIAK Switzerland, and Bayer Pharma.
1242-1249
Mathers, John C.
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Movahedi, Mohammad
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Macrae, Finlay
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Mecklin, Jukka-Pekka
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Moeslein, Gabriela
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Olschwang, Sylviane
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Eccles, Diana
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Evans, Gareth
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Maher, Eamonn R
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Bertario, Lucio
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Bisgaard, Marie-Luise
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Dunlop, Malcolm
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Ho, Judy W.C.
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Hodgson, Shirley
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Lindblom, Annika
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Lubinski, Jan
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Morrison, Patrick J.
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Murday, Victoria
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Ramesar, Raj
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Side, Lucy
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Scott, Rodney J.
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Thomas, Huw J.W.
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Vasen, Hans
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Gerdes, Anne-Marie
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Barker, Gail
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Crawford, Gillian
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Elliott, Faye
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Pylvanainen, Kirsi
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Wijnen, Juul
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Fodde, Riccardo
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Lynch, Henry
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Bishop, D. Timothy
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Burn, John
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CAPP2 Investigators
Mathers, John C.
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Movahedi, Mohammad
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Macrae, Finlay
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Mecklin, Jukka-Pekka
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Moeslein, Gabriela
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Olschwang, Sylviane
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Eccles, Diana
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Evans, Gareth
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Maher, Eamonn R
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Bertario, Lucio
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Dunlop, Malcolm
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Ho, Judy W.C.
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Lindblom, Annika
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Lubinski, Jan
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Morrison, Patrick J.
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Murday, Victoria
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Ramesar, Raj
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Side, Lucy
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Scott, Rodney J.
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Thomas, Huw J.W.
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Vasen, Hans
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Gerdes, Anne-Marie
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Barker, Gail
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Crawford, Gillian
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Elliott, Faye
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Pylvanainen, Kirsi
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Wijnen, Juul
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Fodde, Riccardo
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Lynch, Henry
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Bishop, D. Timothy
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Burn, John
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Mathers, John C., Movahedi, Mohammad, Macrae, Finlay, Mecklin, Jukka-Pekka, Moeslein, Gabriela, Olschwang, Sylviane, Eccles, Diana, Evans, Gareth, Maher, Eamonn R, Bertario, Lucio, Bisgaard, Marie-Luise, Dunlop, Malcolm, Ho, Judy W.C., Hodgson, Shirley, Lindblom, Annika, Lubinski, Jan, Morrison, Patrick J., Murday, Victoria, Ramesar, Raj, Side, Lucy, Scott, Rodney J., Thomas, Huw J.W., Vasen, Hans, Gerdes, Anne-Marie, Barker, Gail, Crawford, Gillian, Elliott, Faye, Pylvanainen, Kirsi, Wijnen, Juul, Fodde, Riccardo, Lynch, Henry, Bishop, D. Timothy and Burn, John , CAPP2 Investigators (2012) Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet Oncology, 13 (12), 1242-1249. (doi:10.1016/S1470-2045(12)70475-8). (PMID:23140761)

Record type: Article

Abstract

BACKGROUND: Observational studies report that higher intake of dietary fibre (a heterogeneous mix including non-starch polysaccharides and resistant starches) is associated with reduced risk of colorectal cancer, but no randomised trials with prevention of colorectal cancer as a primary endpoint have been done. We assessed the effect of resistant starch on the incidence of colorectal cancer.

METHODS: In the CAPP2 study, individuals with Lynch syndrome were randomly assigned in a two-by-two factorial design to receive 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was done with a block size of 16. Post-intervention, patients entered into double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint for this analysis was development of colorectal cancer in participants randomly assigned to resistant starch or resistant-starch placebo with both intention-to-treat and per-protocol analyses. This study is registered, ISRCTN 59521990.

FINDINGS: 463 patients were randomly assigned to receive resistant starch and 455 to receive resistant-starch placebo. At a median follow-up 52·7 months (IQR 28·9-78·4), 53 participants developed 61 primary colorectal cancers (27 of 463 participants randomly assigned to resistant starch, 26 of 455 participants assigned to resistant-starch placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 1·40 (95% CI 0·78-2·56; p=0·26) and Poisson regression accounting for multiple primary events gave an incidence rate ratio (IRR) of 1·15 (95% CI 0·66-2·00; p=0·61). For those completing 2 years of intervention, per-protocol analysis yielded a HR of 1·09 (0·55-2·19, p=0·80) and an IRR of 0·98 (0·51-1·88, p=0·95). No information on adverse events was gathered during post-intervention follow-up.

INTERPRETATION: Resistant starch had no detectable effect on cancer development in carriers of hereditary colorectal cancer. Dietary supplementation with resistant starch does not emulate the apparently protective effect of diets rich in dietary fibre against colorectal cancer.

FUNDING: European Union, Cancer Research UK, Bayer Corporation, National Starch and Chemical Co, UK Medical Research Council, Newcastle Hospitals Trustees, Cancer Council of Victoria Australia, THRIPP South Africa, The Finnish Cancer Foundation, SIAK Switzerland, and Bayer Pharma.

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e-pub ahead of print date: 7 November 2012
Published date: December 2012
Organisations: Cancer Sciences

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Local EPrints ID: 349557
URI: https://eprints.soton.ac.uk/id/eprint/349557
PURE UUID: 35e13f37-5bdb-4174-a747-2b3a129c0612

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Date deposited: 07 Mar 2013 10:17
Last modified: 22 Jul 2019 16:31

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Contributors

Author: John C. Mathers
Author: Mohammad Movahedi
Author: Finlay Macrae
Author: Jukka-Pekka Mecklin
Author: Gabriela Moeslein
Author: Sylviane Olschwang
Author: Diana Eccles
Author: Gareth Evans
Author: Eamonn R Maher
Author: Lucio Bertario
Author: Marie-Luise Bisgaard
Author: Malcolm Dunlop
Author: Judy W.C. Ho
Author: Shirley Hodgson
Author: Annika Lindblom
Author: Jan Lubinski
Author: Patrick J. Morrison
Author: Victoria Murday
Author: Raj Ramesar
Author: Lucy Side
Author: Rodney J. Scott
Author: Huw J.W. Thomas
Author: Hans Vasen
Author: Anne-Marie Gerdes
Author: Gail Barker
Author: Faye Elliott
Author: Kirsi Pylvanainen
Author: Juul Wijnen
Author: Riccardo Fodde
Author: Henry Lynch
Author: D. Timothy Bishop
Author: John Burn

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