title: The Influence of BRAF and KRAS Mutation Status on the Association between Aspirin Use and Survival after Colon Cancer Diagnosis.
abstract: BACKGROUND
  Use of aspirin after diagnosis of colon cancer has been associated with improved survival. Identification of cancer subtypes that respond to aspirin treatment may help develop personalized treatment regimens. The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis.
  
  
  METHODS
  A random selection of 599 patients with colon cancer were analyzed, selected from the Eindhoven Cancer Registry, and BRAF and KRAS mutation status was determined. Data on aspirin use (80 mg) were obtained from the PHARMO Database Network. Parametric survival models with exponential (Poisson) distribution were used.
  
  
  RESULTS
  Aspirin use after colon cancer diagnosis was associated with improved overall survival in wild-type BRAF tumors, adjusted rate ratio (RR) of 0.60 (95% CI 0.44-0.83). In contrast, aspirin use in BRAF mutated tumors was not associated with an improved survival (RR 1.11, 95% CI 0.57-2.16). P-value for interaction was non-significant. KRAS mutational status did not differentiate in the association between aspirin use and survival.
  
  
  CONCLUSIONS
  Low-dose aspirin use after colon cancer diagnosis was associated with improved survival in BRAF wild-type tumors only. However, the large confidence interval of the rate ratio for the use of aspirin in patients with BRAF mutation does not rule out a possible benefit. These results preclude BRAF and KRAS mutation status to be used as a marker for individualized treatment with aspirin, if aspirin becomes regular adjuvant treatment for colon cancer patients in the future.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martine A
authors.identifier: http://orcid.org/0000-0002-6139-9524
authors.initials: MA
authors.lastname: Frouws
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marlies S
authors.initials: MS
authors.lastname: Reimers
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marloes
authors.initials: M
authors.lastname: Swets
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Bastiaannet
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Bianca
authors.initials: B
authors.lastname: Prinse
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Eijk
authors.affiliation: Comprehensive Cancer Organisation The Netherlands, Eindhoven, The Netherlands.|Department of Public Health, Erasmus MC Medical Centre, Rotterdam, The Netherlands.
authors.forename: Valery E P P
authors.initials: VE
authors.lastname: Lemmens
authors.affiliation: PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
authors.forename: Myrthe P P
authors.initials: MP
authors.lastname: van Herk-Sukel
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van Wezel
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Liefers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012042:Registries; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D001241:Aspirin