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Patient and Tumor Characteristics and BRAF and KRAS Mutations in ColonCancer, NCCTG/Alliance N0147.
Journal of the National Cancer Institute
  • Wilson I Gonsalves, Division of Hematology/Division of Medical Oncology
  • Michelle R Mahoney, Division of Biomedical Statistics & Informatics
  • Daniel J Sargent, Cancer Center Statistics
  • Garth D Nelson, Division of Biomedical Statistics & Informatics
  • Steven R Alberts, Mayo Clinic Rochester, Rochester, MN
  • Frank A Sinicrope, Division of Gastroenterology & Hepatology/Division of Medical Oncology
  • Richard M Goldberg, Mayo Clinic, Rochester, MN
  • Paul J Limburg, Division of Gastroenterology & Hepatology
  • Stephen N Thibodeau, Molecular Genetics
  • Axel Grothey, Division of Medical Oncology
  • Joleen M Hubbard, Division of Medical Oncology
  • Emily Chan, Division of Hematology/Oncology, Vanderbilt University, Nashville, TN.
  • Suresh G Nair, MD, Lehigh Valley Health Network
  • Jeffrey L Berenberg, Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI
  • Robert R McWilliams, Division of Medical Oncology
Publication/Presentation Date

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.

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Citation Information

Gonsalves, W. I., Mahoney, M. R., Sargent, D. J., Nelson, G. D., Alberts, S. R., Sinicrope, F. A., & ... McWilliams, R. R. (2014). Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147. Journal Of The National Cancer Institute, 106(7), doi:10.1093/jnci/dju106