Colorectal Adenoma/carcinoma Prevention Project 2 (CAPP2): RCT of aspirin and resistant starch in HNPCC(Lynch Syndrome)

Lead Research Organisation: Newcastle University
Department Name: Institute of Human Genetics

Abstract

Bowel cancer starts as a small lump or polyp, when a cell in the bowel wall grows out of control. This happens when several genes that control cell growth are faulty. Genes are codes that control how our bodies work, and can be damaged in a single cell by factors such as diet. Some families are more prone to bowel cancer because they have inherited a fault in a gene. People with Lynch syndrome, who don?t get many polyps but have a high chance of getting bowel cancer can be recognised using medical and family history and genetic testing. They have an error in a ?mismatch repair? gene whose job it is to ?spell check? other genes when they are copied to make new cells. When one of the mismatch repair genes fails, thousands of errors develop in other genes and this can lead to cancer. Taking regular aspirin seems to make people less likely to get bowel cancer and it also stops human and animal cancer cells growing in the laboratory. Aspirin seems to work particularly well on cells where the mismatch repair genes don?t work. Eating starchy food appears to reduce the risk of bowel cancer, especially if it reaches the bowel undigested, when it is called ?resistant starch?. Resistant starch is broken down in the bowel to make butyrate, a small molecule known to kill bowel cancer cells. Because aspirin has side effects, before we suggest people take it regularly or add starch to their food to prevent bowel cancer, we need to be sure that it really works. We have chosen to test it in people with Lynch syndrome because they are very likely to get polyps or cancer, and they are having regular bowel checks already. They are also very keen to help because it affects their families. The CAPP2 Study will test if aspirin and/or resistant starch can prevent polyps. We will ask 1,350 people with Lynch syndrome to take 2 tablets and 2 starch sachets daily for 2 to 4 years. The people in the study, and the researchers, will not know if the tablets and starch are active or harmless substitutes, so that we can be sure it is the treatments and not something else which is making the difference. We have recruited 450 people so far and will have a final answer by 2007.

Technical Summary

A chemoprevention trial targeted at adults with Lynch syndrome, a monogenic form of colorectal cancer, this study has a randomised, placebo controlled factorial design. It will test the efficacy of two interventions for which there is strong indirect support; aspirin (600mg) and resistant starch(30g).A 3 year EU funded initial study has established the protocol and recruited 450, one third of the target number.

Publications

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Bertagnolli MM (2009) Five-year efficacy and safety analysis of the Adenoma Prevention with Celecoxib Trial. in Cancer prevention research (Philadelphia, Pa.)

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Borthwick GM (2006) Therapeutic levels of aspirin and salicylate directly inhibit a model of angiogenesis through a Cox-independent mechanism. in FASEB journal : official publication of the Federation of American Societies for Experimental Biology

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Burn J (2012) Lynch syndrome: history, causes, diagnosis, treatment and prevention (CAPP2 trial). in Digestive diseases (Basel, Switzerland)

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Burn J (2013) Chemoprevention in Lynch syndrome. in Familial cancer

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Cuzick J (2015) Estimates of benefits and harms of prophylactic use of aspirin in the general population. in Annals of oncology : official journal of the European Society for Medical Oncology

 
Description CRUK Cancer Prevention Research Strategy Consultation
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Clinical Advisory Group for Lynch syndrome testing
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact A handbook, was issued in November 2020 to the Cancer Alliances: Implementing Lynch Syndrome testing and surveillance.
URL https://rmpartners.nhs.uk/wp-content/uploads/2020/12/Lynch_syndrome_handbook_for_Alliances_FINAL-1.p...
 
Description INTERNATIONAL CONSENSUS GROUP
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
 
Description MRC Nutrition and Health Review Workshop, 7th - 8th July 2016
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description MRC Review of Nutrition and Human Health Research, 14 Oct 2016
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description MRC Review of Nutrition and Human Health research - 17th March
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Guideline Title Lynch syndrome: taking aspirin to reduce the chance of getting bowel cancer: Patient decision aid
Description NICE guidelines on aspirin for genetically predisposed to bowel cancer
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact The impact applies to all persons with Lynch Syndrome, an autosomal dominant syndrome associated with bowel cancer and other cancers. The syndrome is due to a germline mutation in a mismatch repair gene. We showed that taking regular aspirin 600mg per day halved the risk of colorectal cancer after about 4 years from starting taking aspirin regularly. It has been estimated that there are 175,000 patients in the UK but less than 5% are clinically known - however it is clear that an increasing proportion of patients are being recognised.
 
Description Submitted to NICE Consultation : colorectal cancer : diagnosis & management. Recommended that adults with a pathogenic mismatch repair gene defect predisposing to Lynch syndrome should be advised that there is convincing evidence that daily aspirin reduces the risk of colorectal and other cancers associated with this condition.
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description World Cancer Research Fund International Grants Panel (panel member). London. June 2019
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
URL https://www.wcrf-uk.org/
 
Description CTAAC
Amount £1,427,802 (GBP)
Funding ID C1297/A15934 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2013 
End 08/2023
 
Description 50th Korean Nutrition Society Annual Meeting. Korea. Nov 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Celebration of Korean Nutrition Society's 50th Anniversary. Opportunity to showcase UK science to international colleagues and to discuss opportbnities for collaboration.
Year(s) Of Engagement Activity 2017
URL http://kns2017.org/invitation.asp
 
Description AliveAndKickn Podcast (for Lynch Syndrome patient group) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Podcast/ radio broadcast on the CaPP3 aspirin study
Audience members are patients who have Lynch Syndrome, the podcast provides guidance, updates, research and insight for those with Lynch Syndrome.
Year(s) Of Engagement Activity 2020
URL https://www.aliveandkickn.org/podcast/episode/1d2afc38/aliveandkickn-podcast-professor-sir-john-burn
 
Description BBC RADIO 4 CASE NOTES 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact INTERVIEW ALONGSIDE THE FIRST RECRUIT TO THE TRIAL

WILL NOT BE BROADCAST UNTIL 2010
Year(s) Of Engagement Activity 2009
 
Description BBC Radio 4 Life Scientific 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact John Burn and the genetics of cancer on BBC Radio 4's Life Scientific, Broadcast Tuesday 20th February 2018, available via podcast
Year(s) Of Engagement Activity 2018
URL http://www.bbc.co.uk/programmes/b09rxr3t
 
Description CAPP2 WEBSITE 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact OUTCOME OF TRIAL MADE AVAILABLE ON CAPP2 WEBSITE

WIDER APPRECIATION OF THIS NOVEL INTERNATIONAL CHEMOPREVENTION TRIAL
Year(s) Of Engagement Activity 2008
 
Description EHTG Barcelona. "A new look at the role of dietary fibre in cancer prevention". Barcelona, Spain 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of new findings from the CAPP2 Study long-term follow-up
Year(s) Of Engagement Activity 2019
 
Description Harveian Oration 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Yearly lecture held at the Royal College of Physicians of London.
Title: Prediction and prevention in the genomic era
Year(s) Of Engagement Activity 2019
URL http://rcplondon.ac.uk/projects/harveian-oration
 
Description Interviews for Rare Disease Day 28th February 2018: CaPP3 study 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact CaPP3 study CI and patient interview: Interviews for national media on behalf of the NIHR campaign for Rare Disease Day 2018. Interviewed by several radio stations from the NIHR media base in London on 28.02.18. Prior to the day the NIHR filmed interviews about the CaPP3 study, 100,000 Genomes project and the Musketeers' Memorandum. The Cancer Prevention Programme office received many email email queries and phone calls after the media coverage. The links on the CaPP3 website were made available to international collaborators as well as patient groups.
Year(s) Of Engagement Activity 2018
URL https://www.nihr.ac.uk/news-and-events/support-our-campaigns/rare-disease-day-2018/lynch-syndrome.ht...
 
Description Lectures & Presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lectures & Presentations (30+) in 2017/2018 to a range of audiences.
Year(s) Of Engagement Activity 2019
 
Description Lectures & Presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lectures & Presentations (50+) to a range of audiences.
Year(s) Of Engagement Activity 2020
 
Description Lectures & Presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Many lectures and presentations to various groups around the world.
All virtual due to COVID-19 restrictions
Year(s) Of Engagement Activity 2020,2021
 
Description Module "Recent topics in Nutrition Research" at University of Munich. Lecture title: "Obesity and bowel cancer". Germany 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Discussion with PG students about potential internships in Newcastle University.
Discussion with academic colleagues about potential research collaboration.
Year(s) Of Engagement Activity 2016
 
Description Nutrition Society Symposium. 'Obesity and bowel cancer: mechanisms to interventions' 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact More than 50 participants attended the lecture. This led to discussion with several research groups afterwards and requests for collaboration.
Year(s) Of Engagement Activity 2018