TY - JOUR
T1 - Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147
AU - Gonsalves, Wilson I.
AU - Mahoney, Michelle R.
AU - Sargent, Daniel J.
AU - Nelson, Garth D.
AU - Alberts, Steven R.
AU - Sinicrope, Frank A.
AU - Goldberg, Richard M.
AU - Limburg, Paul J.
AU - Thibodeau, Stephen N.
AU - Grothey, Axel
AU - Hubbard, Joleen M.
AU - Chan, Emily
AU - Nair, Suresh
AU - Berenberg, Jeffrey L.
AU - McWilliams, Robert R.
N1 - Funding Information:
This trial was conducted as a collaborative trial of the North Central Cancer Treatment Group [NCCTG Legacy (Alliance)] and Mayo Clinic and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-35103, CA-63844, CA-35113, CA-35272, CA-114740, CA-32102, CA-14028, CA49957, CA21115, CA31946, CA12027, CA37377 from the National Cancer Institute, Department of Health and Human Services. Bristol-Myers Squibb, ImClone, sanofi-aventis, and Pfizer provided unrestricted support to the NCCTG for conduct of this trial.
PY - 2014/7/9
Y1 - 2014/7/9
N2 - 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.
AB - 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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U2 - 10.1093/jnci/dju106
DO - 10.1093/jnci/dju106
M3 - Article
C2 - 24925349
AN - SCOPUS:84905259995
SN - 0027-8874
VL - 106
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 7
M1 - dju106
ER -