title: Racial Differences in BRAF/KRAS Mutation Rates and Survival in Stage III Colon Cancer Patients.
abstract: BACKGROUND
  It is unknown if, after controlling for clinicopathologic variables and treatment, racial disparities in colon cancer outcomes persist. Molecular marker analysis in North American patients comparing Asians with other races has not been reported.
  
  
  METHODS
  BRAF (V600E) and KRAS mutations were analyzed in node-positive colon cancer patients (n = 3305) treated with FOLFOX-based chemotherapy in an adjuvant trial (Alliance N0147). Race categories included Asian, black, or white. Cox models were used to estimate disease-free survival (DFS) and time to recurrence (TTR). All statistical tests were two-sided.
  
  
  RESULTS
  BRAF mutation frequency in tumors from whites (13.9%) was twice that of tumors from Asians or blacks. KRAS mutation rates were highest in tumors from blacks (44.1%). KRAS/BRAF wild-type tumors were most common among Asians (66.7%) (P overall < .001). The prognostic impact of race differed by age and N stage (both P interaction < .02). Compared with whites, blacks had shorter DFS among patients younger than age 50 years (hazard ratio [HR] = 2.84, 95% confidence interval [CI] = 1.73 to 4.66) or with N1 disease (HR = 1.54, 95% CI = 1.04 to 2.29), independent of BRAF, KRAS, and other covariates. Findings were consistent using TTR as the outcome. Asians had longer DFS among N2 tumors that was partly mediated by less frequent BRAF mutation.
  
  
  CONCLUSIONS
  Colon cancers from Asians have a lower rate of BRAF and KRAS mutations than blacks or whites. We report a novel interaction of race with age and N stage in node-positive disease, indicating that racial disparities in survival persist despite uniform stage and treatment in a phase III trial.
authors.affiliation: Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG). yoon.harry@mayo.edu sinicrope.frank@mayo.edu.
authors.forename: Harry H
authors.initials: HH
authors.lastname: Yoon
authors.affiliation: Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG).
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG).
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.affiliation: Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG).
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.affiliation: Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG).
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG).
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.affiliation: Mayo Clinic, Rochester, MN (HHY, SRA, SNT, FAS); Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (QS, DJS); Division of Medical Oncology, The Ohio State University, Columbus, OH (RMG). yoon.harry@mayo.edu sinicrope.frank@mayo.edu.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D003110:Colonic Neoplasms / Q000208:ethnology* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D015986:Confounding Factors, Epidemiologic; D053843:DNA Mismatch Repair; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)