title: Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
authors.affiliation: Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK. john.mathers@ncl.ac.uk
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
authors.forename: Mohammad
authors.initials: M
authors.lastname: Movahedi
authors.forename: Finlay
authors.initials: F
authors.lastname: Macrae
authors.forename: Jukka-Pekka
authors.initials: JP
authors.lastname: Mecklin
authors.forename: Gabriela
authors.initials: G
authors.lastname: Moeslein
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.forename: Gareth
authors.initials: G
authors.lastname: Evans
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: Lucio
authors.initials: L
authors.lastname: Bertario
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Bisgaard
authors.forename: Malcolm
authors.initials: M
authors.lastname: Dunlop
authors.forename: Judy W C
authors.initials: JW
authors.lastname: Ho
authors.forename: Shirley
authors.initials: S
authors.lastname: Hodgson
authors.forename: Annika
authors.initials: A
authors.lastname: Lindblom
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Morrison
authors.forename: Victoria
authors.initials: V
authors.lastname: Murday
authors.forename: Raj
authors.initials: R
authors.lastname: Ramesar
authors.forename: Lucy
authors.initials: L
authors.lastname: Side
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.forename: Huw J W
authors.initials: HJ
authors.lastname: Thomas
authors.forename: Hans
authors.initials: H
authors.lastname: Vasen
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Gerdes
authors.forename: Gail
authors.initials: G
authors.lastname: Barker
authors.forename: Gillian
authors.initials: G
authors.lastname: Crawford
authors.forename: Faye
authors.initials: F
authors.lastname: Elliott
authors.forename: Kirsi
authors.initials: K
authors.lastname: Pylvanainen
authors.forename: Juul
authors.initials: J
authors.lastname: Wijnen
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.forename: Henry
authors.initials: H
authors.lastname: Lynch
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: John
authors.initials: J
authors.lastname: Burn
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000517:prevention & control; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000517:prevention & control*; D004040:Dietary Carbohydrates / Q000627:therapeutic use*; D004043:Dietary Fiber / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D013213:Starch / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D004040:Dietary Carbohydrates; D004043:Dietary Fiber; D013213:Starch