title: KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers.
abstract: BACKGROUND
  Mutations in the Kirsten Ras (KRAS) oncogene are common in colorectal cancer (CRC). The role of KRAS-mutation status as a prognostic factor, however, is unclear. We evaluated the relationship between KRAS-mutation status and CRC survival, considering heterogeneity in this association by tumour and patient characteristics.
  
  
  METHODS
  The population-based study included individuals diagnosed with CRC between 1998-2007 in Western Washington State. Tumour specimens were tested for KRAS exon 2 mutations, the BRAF p.V600E mutation, and microsatellite instability (MSI). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between KRAS-mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumour site, stage, and MSI. We conducted additional analyses combining KRAS-mutation, BRAF-mutation, and MSI status.
  
  
  RESULTS
  Among 1989 cases, 31% had KRAS-mutated CRC. Kirsten Ras (KRAS)-mutated CRC was associated with poorer disease-specific survival (HR=1.37, 95% CI: 1.13-1.66). This association was not evident in cases who presented with distant-stage CRC. Cases with KRAS-wild-type/BRAF-wild-type/MSI-high CRC had the most favourable prognosis; those with CRC exhibiting a KRAS- or BRAF-mutation and no MSI had the poorest prognosis. Patterns were similar for overall survival.
  
  
  CONCLUSIONS
  Kirsten Ras (KRAS)-mutated CRC was associated with statistically significantly poorer survival after diagnosis than KRAS-wild-type CRC.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA. aphipps@fhcrc.org
authors.forename: A I
authors.initials: AI
authors.lastname: Phipps
authors.forename: D D
authors.initials: DD
authors.lastname: Buchanan
authors.forename: K W
authors.initials: KW
authors.lastname: Makar
authors.forename: A K
authors.initials: AK
authors.lastname: Win
authors.forename: J A
authors.initials: JA
authors.lastname: Baron
authors.forename: N M
authors.initials: NM
authors.lastname: Lindor
authors.forename: J D
authors.initials: JD
authors.lastname: Potter
authors.forename: P A
authors.initials: PA
authors.lastname: Newcomb
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018426:SEER Program; D015996:Survival Rate; D014861:Washington / Q000453:epidemiology; D055815:Young Adult