Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147

Wilson Gonsalves, Michelle R. Mahoney, Daniel J. Sargent, Garth D. Nelson, Steven Robert Alberts, Frank A Sinicrope, Richard M. Goldberg, Paul John Limburg, Stephen N Thibodeau, Axel F Grothey, Joleen M Hubbard, Emily Chan, Suresh Nair, Jeffrey L. Berenberg, Robert R Mc Williams

Research output: Contribution to journalArticle

74 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberdju106
JournalJournal of the National Cancer Institute
Volume106
Issue number7
DOIs
StatePublished - Jul 9 2014

Fingerprint

Colonic Neoplasms
Mutation
DNA Mismatch Repair
Neoplasms
Odds Ratio
Confidence Intervals
Histology
Logistic Models
Lymph Nodes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147. / Gonsalves, Wilson; Mahoney, Michelle R.; Sargent, Daniel J.; Nelson, Garth D.; Alberts, Steven Robert; Sinicrope, Frank A; Goldberg, Richard M.; Limburg, Paul John; Thibodeau, Stephen N; Grothey, Axel F; Hubbard, Joleen M; Chan, Emily; Nair, Suresh; Berenberg, Jeffrey L.; Mc Williams, Robert R.

In: Journal of the National Cancer Institute, Vol. 106, No. 7, dju106, 09.07.2014.

Research output: Contribution to journalArticle

@article{c28a502290824d90a339783c22fb5129,
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.",
author = "Wilson Gonsalves and Mahoney, {Michelle R.} and Sargent, {Daniel J.} and Nelson, {Garth D.} and Alberts, {Steven Robert} and Sinicrope, {Frank A} and Goldberg, {Richard M.} and Limburg, {Paul John} and Thibodeau, {Stephen N} and Grothey, {Axel F} and Hubbard, {Joleen M} and Emily Chan and Suresh Nair and Berenberg, {Jeffrey L.} and {Mc Williams}, {Robert R}",
year = "2014",
month = "7",
day = "9",
doi = "10.1093/jnci/dju106",
language = "English (US)",
volume = "106",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "7",

}

TY - JOUR

T1 - Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147

AU - Gonsalves, Wilson

AU - Mahoney, Michelle R.

AU - Sargent, Daniel J.

AU - Nelson, Garth D.

AU - Alberts, Steven Robert

AU - Sinicrope, Frank A

AU - Goldberg, Richard M.

AU - Limburg, Paul John

AU - Thibodeau, Stephen N

AU - Grothey, Axel F

AU - Hubbard, Joleen M

AU - Chan, Emily

AU - Nair, Suresh

AU - Berenberg, Jeffrey L.

AU - Mc Williams, Robert R

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.

UR - http://www.scopus.com/inward/record.url?scp=84905259995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905259995&partnerID=8YFLogxK

U2 - 10.1093/jnci/dju106

DO - 10.1093/jnci/dju106

M3 - Article

C2 - 24925349

AN - SCOPUS:84905259995

VL - 106

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 7

M1 - dju106

ER -