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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1242-1249
Number of pages8
JournalThe Lancet Oncology
Volume13
Issue number12
DOIs
StatePublished - Dec 2012

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Starch
Colorectal Neoplasms
Randomized Controlled Trials
Neoplasms
Placebos
Dietary Fiber
Aspirin
Incidence
Hereditary Nonpolyposis Colorectal Neoplasms
Trustees
Cancer Care Facilities
Intention to Treat Analysis
Victoria
European Union
Random Allocation
Dietary Supplements
South Africa
Switzerland
Observational Studies
Polysaccharides

All Science Journal Classification (ASJC) codes

  • Oncology

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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. / 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 T.; Bishop, D. Timothy; Burn, John.

In: The Lancet Oncology, Vol. 13, No. 12, 12.2012, p. 1242-1249.

Research output: Contribution to journalArticle

Mathers, JC, Movahedi, M, Macrae, F, Mecklin, JP, Moeslein, G, Olschwang, S, Eccles, D, Evans, G, Maher, ER, Bertario, L, Bisgaard, ML, Dunlop, M, Ho, JWC, Hodgson, S, Lindblom, A, Lubinski, J, Morrison, PJ, Murday, V, Ramesar, R, Side, L, Scott, RJ, Thomas, HJW, Vasen, H, Gerdes, AM, Barker, G, Crawford, G, Elliott, F, Pylvanainen, K, Wijnen, J, Fodde, R, Lynch, HT, Bishop, DT & Burn, J 2012, 'Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: An analysis from the CAPP2 randomised controlled trial', The Lancet Oncology, vol. 13, no. 12, pp. 1242-1249. https://doi.org/10.1016/S1470-2045(12)70475-8
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 T. ; Bishop, D. Timothy ; Burn, John. / Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer : An analysis from the CAPP2 randomised controlled trial. In: The Lancet Oncology. 2012 ; Vol. 13, No. 12. pp. 1242-1249.
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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.",
author = "Mathers, {John C.} and Mohammad Movahedi and Finlay Macrae and Mecklin, {Jukka Pekka} and Gabriela Moeslein and Sylviane Olschwang and Diana Eccles and Gareth Evans and Maher, {Eamonn R.} and Lucio Bertario and Bisgaard, {Marie Luise} and Malcolm Dunlop and Ho, {Judy W C} and Shirley Hodgson and Annika Lindblom and Jan Lubinski and Morrison, {Patrick J.} and Victoria Murday and Raj Ramesar and Lucy Side and Scott, {Rodney J.} and Thomas, {Huw J W} and Hans Vasen and Gerdes, {Anne Marie} and Gail Barker and Gillian Crawford and Faye Elliott and Kirsi Pylvanainen and Juul Wijnen and Riccardo Fodde and Lynch, {Henry T.} and Bishop, {D. Timothy} and John Burn",
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TY - JOUR

T1 - Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer

T2 - An analysis from the CAPP2 randomised controlled trial

AU - Mathers, John C.

AU - Movahedi, Mohammad

AU - Macrae, Finlay

AU - Mecklin, Jukka Pekka

AU - Moeslein, Gabriela

AU - Olschwang, Sylviane

AU - Eccles, Diana

AU - Evans, Gareth

AU - Maher, Eamonn R.

AU - Bertario, Lucio

AU - Bisgaard, Marie Luise

AU - Dunlop, Malcolm

AU - Ho, Judy W C

AU - Hodgson, Shirley

AU - Lindblom, Annika

AU - Lubinski, Jan

AU - Morrison, Patrick J.

AU - Murday, Victoria

AU - Ramesar, Raj

AU - Side, Lucy

AU - Scott, Rodney J.

AU - Thomas, Huw J W

AU - Vasen, Hans

AU - Gerdes, Anne Marie

AU - Barker, Gail

AU - Crawford, Gillian

AU - Elliott, Faye

AU - Pylvanainen, Kirsi

AU - Wijnen, Juul

AU - Fodde, Riccardo

AU - Lynch, Henry T.

AU - Bishop, D. Timothy

AU - Burn, John

PY - 2012/12

Y1 - 2012/12

N2 - 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.

AB - 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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