title: Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer.
abstract: OBJECTIVE
  To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability (MSI) status in Japanese colorectal cancer (CRC) population.
  
  
  METHODS
  We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage I-III CRC and examined associations of these mutations with disease-free survival (DFS) and overall survival (OS) using uni- and multivariate Cox proportional hazards models.
  
  
  RESULTS
  KRAS and BRAF mutations were detected in 312 (38%) of 812 and 40 (5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males (P=0.02), while the presence of BRAF mutations was significantly associated with the female gender (P=0.006), proximal tumor location (P<0.001), mucinous or poorly differentiated histology (P<0.001), and MSI-high tumors (P<0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS (HR=1.35; 95%CI: 1.03-1.75) and OS (HR=1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS (HR=2.20; 95%CI: 1.19-4.06) and OS (HR=2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.
  
  
  CONCLUSIONS
  KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, in Japanese patients with curatively resected CRC.
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Shigenori
authors: S
authors: Kadowaki
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Miho
authors: M
authors: Kakuta
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Shuhei
authors: S
authors: Takahashi
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Akemi
authors: A
authors: Takahashi
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Yoshiko
authors: Y
authors: Arai
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Yoji
authors: Y
authors: Nishimura
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Toshimasa
authors: T
authors: Yatsuoka
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Akira
authors: A
authors: Ooki
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Kensei
authors: K
authors: Yamaguchi
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Keitaro
authors: K
authors: Matsuo
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Kei
authors: K
authors: Muro
authors: Shigenori Kadowaki, Akira Ooki, Kensei Yamaguchi, Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors: Kiwamu
authors: K
authors: Akagi
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D003082:Colectomy / Q000009:adverse effects / Q000401:mortality; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D013997:Time Factors; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: BRAF; Colorectal cancer; KRAS; Microsatellite instability; Prognostic factor
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