title: Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer.
abstract: BACKGROUND
  Activating mutations in KRAS have been suggested as potential predictive and prognostic biomarkers. However, the prognostic impact of specific point mutations remains less clear. This study assessed the prognostic impact of specific KRAS mutations on survival for patients with colorectal cancer.
  
  
  METHODS
  Retrospective review of patients KRAS typed for advanced and recurrent colorectal cancer between 2010 and 2015 in a UK Cancer Network.
  
  
  RESULTS
  We evaluated the impact of KRAS genotype in 392 patients. Mutated KRAS was detected in 42.9% of tumours. KRAS mutations were more common in moderate vs well-differentiated tumours. On multivariate analysis, primary tumour T stage (HR 2.77 (1.54-4.98), P=0.001), N stage (HR 1.51 (1.01-2.26), P=0.04), curative intent surgery (HR 0.51 (0.34-0.76), P=0.001), tumour grade (HR 0.44 (0.30-0.65), P=0.001) and KRAS mutation (1.54 (1.23-2.12), P=0.005) were all predictive of overall survival. Patients with KRAS codon 12 mutations had worse overall survival (HR 1.76 (95% CI 1.27-2.43), P=0.001). Among the five most common codon 12 mutations, only p.G12C (HR 2.21 (1.15-4.25), P=0.01) and p.G12V (HR 1.69 (1.08-2.62), P=0.02) were predictive of overall survival.
  
  
  CONCLUSIONS
  For patients with colorectal cancer, p.G12C and p.G12V mutations in codon 12 were independently associated with worse overall survival after diagnosis.
authors.affiliation: North Western Hepatobiliary Unit, Aintree University Hospital, Liverpool, UK.|School of Cancer Studies, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Jones
authors.affiliation: School of Cancer Studies, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.|Department of Surgery, Wirral University Teaching Hospital NHS Foundation Trust, Cheshire, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sutton
authors.affiliation: School of Cancer Studies, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.|Department of Surgery, Wirral University Teaching Hospital NHS Foundation Trust, Cheshire, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Evans
authors.affiliation: Department of Surgery, St. Helens and Knowsley Teaching Hospitals NHS Trust, Merseyside, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Clifford
authors.affiliation: North Western Hepatobiliary Unit, Aintree University Hospital, Liverpool, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: McAvoy
authors.affiliation: Department of Surgery, Wirral University Teaching Hospital NHS Foundation Trust, Cheshire, UK.
authors.forename: James
authors.initials: J
authors.lastname: Lewis
authors.affiliation: Regional Molecular Genetics Laboratory, Liverpool Women's NHS Foundation Trust, Liverpool, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Rousseau
authors.affiliation: Regional Molecular Genetics Laboratory, Liverpool Women's NHS Foundation Trust, Liverpool, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Mountford
authors.affiliation: North Western Hepatobiliary Unit, Aintree University Hospital, Liverpool, UK.|School of Cancer Studies, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: McWhirter
authors.affiliation: North Western Hepatobiliary Unit, Aintree University Hospital, Liverpool, UK.
authors.forename: Hassan Z
authors.initials: HZ
authors.lastname: Malik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)