title: Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147.
abstract: BACKGROUND
  KRAS and BRAF (V600E) mutations are important predictive and prognostic markers, respectively, in colon cancer, but little is known about patient and clinical factors associated with them.
  
  
  METHODS
  Two thousand three hundred twenty-six of 3397 patients in the N0147 phase III adjuvant trial for stage III colon cancer completed a patient questionnaire. Primary tumors were assessed for KRAS and BRAF (V600E) mutations and defective mismatch repair (dMMR) status. Logistic regression models and categorical data analysis were used to identify associations of patient and tumor characteristics with mutation status. All statistical tests were two-sided.
  
  
  RESULTS
  KRAS (35%) and BRAF (V600E) (14%) mutations were nearly mutually exclusive. KRAS mutations were more likely to be present in patients without a family history of colon cancer and never smokers. Tumors with KRAS mutations were less likely to have dMMR (odds ratio [OR] = 0.21; 95% confidence interval [CI] = 0.15 to 0.31; P < .001) and high-grade histology (OR = 0.73; 95% CI = 0.59 to 0.92; P < .001) but were more often right-sided. Among KRAS-mutated tumors, those with a Gly13Asp mutation tended to have dMMR and high-grade histology. Tumors with BRAF (V600E) mutations were more likely to be seen in patients who were aged 70 years or older (OR = 3.33; 95% CI = 2.50 to 4.42; P < .001) and current or former smokers (OR = 1.64; 95% CI = 1.26 to 2.14; P < .001) but less likely in non-whites and men. Tumors with BRAF (V600E) mutations were more likely to be right-sided and to have four or more positive lymph nodes, high-grade histology, and dMMR.
  
  
  CONCLUSIONS
  Specific patient and tumor characteristics are associated with KRAS and BRAF (V600E) mutations.
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Wilson I
authors.initials: WI
authors.lastname: Gonsalves
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Mahoney
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Garth D
authors.initials: GD
authors.lastname: Nelson
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Joleen M
authors.initials: JM
authors.lastname: Hubbard
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Emily
authors.initials: E
authors.lastname: Chan
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Suresh
authors.initials: S
authors.lastname: Nair
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Berenberg
authors.affiliation: Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB). mcwilliams.robert@mayo.edu.
authors.forename: Robert R
authors.initials: RR
authors.lastname: McWilliams
mesh_terms: D000328:Adult; D000368:Aged; D001224:Aspartic Acid; D017326:Clinical Trials, Phase III as Topic; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D053843:DNA Mismatch Repair; D005260:Female; D018698:Glutamic Acid; D005998:Glycine; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D060787:Neoplasm Grading; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011795:Surveys and Questionnaires; D014633:Valine; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D014633:Valine; D005998:Glycine