Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer

An analysis from the CAPP2 randomised controlled trial

John Burn, Anne Marie Gerdes, Finlay MacRae, Jukka Pekka Mecklin, Gabriela Moeslein, Sylviane Olschwang, Diane Eccles, D. Gareth Evans, Eamonn R. Maher, Lucio Bertario, Marie Luise Bisgaard, Malcolm G. Dunlop, Judy W C Ho, Shirley V. Hodgson, Annika Lindblom, Jan Lubinski, Patrick J. Morrison, Victoria Murday, Raj Ramesar, Lucy Side & 13 others Rodney J. Scott, Huw J W Thomas, Hans F. Vasen, Gail Barker, Gillian Crawford, Faye Elliott, Mohammad Movahedi, Kirsi Pylvanainen, Juul T. Wijnen, Riccardo Fodde, Henry T. Lynch, John C. Mathers, D. Timothy Bishop

Research output: Contribution to journalArticle

528 Citations (Scopus)

Abstract

Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95 CI 0·35-1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95 CI 0·32- 0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19-0·86, p=0·02) and an IRR of 0·37 (0·18-0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. 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; Bayer Pharma.

Original languageEnglish
Pages (from-to)2081-2087
Number of pages7
JournalThe Lancet
Volume378
Issue number9809
DOIs
StatePublished - Dec 17 2011

Fingerprint

Aspirin
Colorectal Neoplasms
Randomized Controlled Trials
Neoplasms
Placebos
Starch
Hereditary Nonpolyposis Colorectal Neoplasms
Intention to Treat Analysis
Random Allocation
Incidence
Trustees
Victoria
European Union
South Africa
Switzerland
Adenoma
Antineoplastic Agents
Observational Studies
Biomedical Research
Research Personnel

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Burn, J., Gerdes, A. M., MacRae, F., Mecklin, J. P., Moeslein, G., Olschwang, S., ... Bishop, D. T. (2011). Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: An analysis from the CAPP2 randomised controlled trial. The Lancet, 378(9809), 2081-2087. https://doi.org/10.1016/S0140-6736(11)61049-0

Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer : An analysis from the CAPP2 randomised controlled trial. / Burn, John; Gerdes, Anne Marie; MacRae, Finlay; Mecklin, Jukka Pekka; Moeslein, Gabriela; Olschwang, Sylviane; Eccles, Diane; Evans, D. Gareth; Maher, Eamonn R.; Bertario, Lucio; Bisgaard, Marie Luise; Dunlop, Malcolm G.; Ho, Judy W C; Hodgson, Shirley V.; Lindblom, Annika; Lubinski, Jan; Morrison, Patrick J.; Murday, Victoria; Ramesar, Raj; Side, Lucy; Scott, Rodney J.; Thomas, Huw J W; Vasen, Hans F.; Barker, Gail; Crawford, Gillian; Elliott, Faye; Movahedi, Mohammad; Pylvanainen, Kirsi; Wijnen, Juul T.; Fodde, Riccardo; Lynch, Henry T.; Mathers, John C.; Bishop, D. Timothy.

In: The Lancet, Vol. 378, No. 9809, 17.12.2011, p. 2081-2087.

Research output: Contribution to journalArticle

Burn, J, Gerdes, AM, MacRae, F, Mecklin, JP, Moeslein, G, Olschwang, S, Eccles, D, Evans, DG, Maher, ER, Bertario, L, Bisgaard, ML, Dunlop, MG, Ho, JWC, Hodgson, SV, Lindblom, A, Lubinski, J, Morrison, PJ, Murday, V, Ramesar, R, Side, L, Scott, RJ, Thomas, HJW, Vasen, HF, Barker, G, Crawford, G, Elliott, F, Movahedi, M, Pylvanainen, K, Wijnen, JT, Fodde, R, Lynch, HT, Mathers, JC & Bishop, DT 2011, 'Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: An analysis from the CAPP2 randomised controlled trial', The Lancet, vol. 378, no. 9809, pp. 2081-2087. https://doi.org/10.1016/S0140-6736(11)61049-0
Burn, John ; Gerdes, Anne Marie ; MacRae, Finlay ; Mecklin, Jukka Pekka ; Moeslein, Gabriela ; Olschwang, Sylviane ; Eccles, Diane ; Evans, D. Gareth ; Maher, Eamonn R. ; Bertario, Lucio ; Bisgaard, Marie Luise ; Dunlop, Malcolm G. ; Ho, Judy W C ; Hodgson, Shirley V. ; Lindblom, Annika ; Lubinski, Jan ; Morrison, Patrick J. ; Murday, Victoria ; Ramesar, Raj ; Side, Lucy ; Scott, Rodney J. ; Thomas, Huw J W ; Vasen, Hans F. ; Barker, Gail ; Crawford, Gillian ; Elliott, Faye ; Movahedi, Mohammad ; Pylvanainen, Kirsi ; Wijnen, Juul T. ; Fodde, Riccardo ; Lynch, Henry T. ; Mathers, John C. ; Bishop, D. Timothy. / Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer : An analysis from the CAPP2 randomised controlled trial. In: The Lancet. 2011 ; Vol. 378, No. 9809. pp. 2081-2087.
@article{34648634805545bda53fee60801461bc,
title = "Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: An analysis from the CAPP2 randomised controlled trial",
abstract = "Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95 CI 0·35-1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95 CI 0·32- 0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19-0·86, p=0·02) and an IRR of 0·37 (0·18-0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. 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; Bayer Pharma.",
author = "John Burn and Gerdes, {Anne Marie} and Finlay MacRae and Mecklin, {Jukka Pekka} and Gabriela Moeslein and Sylviane Olschwang and Diane Eccles and Evans, {D. Gareth} and Maher, {Eamonn R.} and Lucio Bertario and Bisgaard, {Marie Luise} and Dunlop, {Malcolm G.} and Ho, {Judy W C} and Hodgson, {Shirley V.} 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 Vasen, {Hans F.} and Gail Barker and Gillian Crawford and Faye Elliott and Mohammad Movahedi and Kirsi Pylvanainen and Wijnen, {Juul T.} and Riccardo Fodde and Lynch, {Henry T.} and Mathers, {John C.} and Bishop, {D. Timothy}",
year = "2011",
month = "12",
day = "17",
doi = "10.1016/S0140-6736(11)61049-0",
language = "English",
volume = "378",
pages = "2081--2087",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9809",

}

TY - JOUR

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

T2 - An analysis from the CAPP2 randomised controlled trial

AU - Burn, John

AU - Gerdes, Anne Marie

AU - MacRae, Finlay

AU - Mecklin, Jukka Pekka

AU - Moeslein, Gabriela

AU - Olschwang, Sylviane

AU - Eccles, Diane

AU - Evans, D. Gareth

AU - Maher, Eamonn R.

AU - Bertario, Lucio

AU - Bisgaard, Marie Luise

AU - Dunlop, Malcolm G.

AU - Ho, Judy W C

AU - Hodgson, Shirley V.

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 F.

AU - Barker, Gail

AU - Crawford, Gillian

AU - Elliott, Faye

AU - Movahedi, Mohammad

AU - Pylvanainen, Kirsi

AU - Wijnen, Juul T.

AU - Fodde, Riccardo

AU - Lynch, Henry T.

AU - Mathers, John C.

AU - Bishop, D. Timothy

PY - 2011/12/17

Y1 - 2011/12/17

N2 - Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95 CI 0·35-1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95 CI 0·32- 0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19-0·86, p=0·02) and an IRR of 0·37 (0·18-0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. 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; Bayer Pharma.

AB - Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95 CI 0·35-1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95 CI 0·32- 0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19-0·86, p=0·02) and an IRR of 0·37 (0·18-0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. 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; Bayer Pharma.

UR - http://www.scopus.com/inward/record.url?scp=83955161674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=83955161674&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(11)61049-0

DO - 10.1016/S0140-6736(11)61049-0

M3 - Article

VL - 378

SP - 2081

EP - 2087

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9809

ER -