Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer

Results of CALGB 89803

Robert S. Warren, Chloe E. Atreya, Donna Niedzwiecki, Vivian K. Weinberg, David B. Donner, Robert J. Mayer, Richard M. Goldberg, Carolyn Compton, Marlene B. Zuraek, Cynthia Ye, Leonard B. Saltz, Monica M. Bertagnolli

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose: The TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA-binding domain of TP53 are associated with survival in stage III colon cancer. Experimental Design: The impact of TP53 genotype was prospectively evaluated in Cancer and Leukemia Group B 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL). Results: TP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease-free survival (DFS) or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type versus zinc- or non-zinc-binding mutations in the TP53 DNA-binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc- or non-zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men. Conclusions: The presence of any TP53 mutation within the DNA-binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men.

Original languageEnglish (US)
Pages (from-to)5777-5787
Number of pages11
JournalClinical Cancer Research
Volume19
Issue number20
DOIs
StatePublished - Oct 15 2013
Externally publishedYes

Fingerprint

Colonic Neoplasms
Survival
Mutation
Genotype
irinotecan
Leucovorin
Therapeutics
Neoplasms
Fluorouracil
Disease-Free Survival
Zinc
DNA
Leukemia
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Warren, R. S., Atreya, C. E., Niedzwiecki, D., Weinberg, V. K., Donner, D. B., Mayer, R. J., ... Bertagnolli, M. M. (2013). Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer: Results of CALGB 89803. Clinical Cancer Research, 19(20), 5777-5787. https://doi.org/10.1158/1078-0432.CCR-13-0351

Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer : Results of CALGB 89803. / Warren, Robert S.; Atreya, Chloe E.; Niedzwiecki, Donna; Weinberg, Vivian K.; Donner, David B.; Mayer, Robert J.; Goldberg, Richard M.; Compton, Carolyn; Zuraek, Marlene B.; Ye, Cynthia; Saltz, Leonard B.; Bertagnolli, Monica M.

In: Clinical Cancer Research, Vol. 19, No. 20, 15.10.2013, p. 5777-5787.

Research output: Contribution to journalArticle

Warren, RS, Atreya, CE, Niedzwiecki, D, Weinberg, VK, Donner, DB, Mayer, RJ, Goldberg, RM, Compton, C, Zuraek, MB, Ye, C, Saltz, LB & Bertagnolli, MM 2013, 'Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer: Results of CALGB 89803', Clinical Cancer Research, vol. 19, no. 20, pp. 5777-5787. https://doi.org/10.1158/1078-0432.CCR-13-0351
Warren, Robert S. ; Atreya, Chloe E. ; Niedzwiecki, Donna ; Weinberg, Vivian K. ; Donner, David B. ; Mayer, Robert J. ; Goldberg, Richard M. ; Compton, Carolyn ; Zuraek, Marlene B. ; Ye, Cynthia ; Saltz, Leonard B. ; Bertagnolli, Monica M. / Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer : Results of CALGB 89803. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 20. pp. 5777-5787.
@article{a6bf2ab2150341dcb49f54ab7fb88bc3,
title = "Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer: Results of CALGB 89803",
abstract = "Purpose: The TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA-binding domain of TP53 are associated with survival in stage III colon cancer. Experimental Design: The impact of TP53 genotype was prospectively evaluated in Cancer and Leukemia Group B 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL). Results: TP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease-free survival (DFS) or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type versus zinc- or non-zinc-binding mutations in the TP53 DNA-binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc- or non-zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men. Conclusions: The presence of any TP53 mutation within the DNA-binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men.",
author = "Warren, {Robert S.} and Atreya, {Chloe E.} and Donna Niedzwiecki and Weinberg, {Vivian K.} and Donner, {David B.} and Mayer, {Robert J.} and Goldberg, {Richard M.} and Carolyn Compton and Zuraek, {Marlene B.} and Cynthia Ye and Saltz, {Leonard B.} and Bertagnolli, {Monica M.}",
year = "2013",
month = "10",
day = "15",
doi = "10.1158/1078-0432.CCR-13-0351",
language = "English (US)",
volume = "19",
pages = "5777--5787",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "20",

}

TY - JOUR

T1 - Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer

T2 - Results of CALGB 89803

AU - Warren, Robert S.

AU - Atreya, Chloe E.

AU - Niedzwiecki, Donna

AU - Weinberg, Vivian K.

AU - Donner, David B.

AU - Mayer, Robert J.

AU - Goldberg, Richard M.

AU - Compton, Carolyn

AU - Zuraek, Marlene B.

AU - Ye, Cynthia

AU - Saltz, Leonard B.

AU - Bertagnolli, Monica M.

PY - 2013/10/15

Y1 - 2013/10/15

N2 - Purpose: The TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA-binding domain of TP53 are associated with survival in stage III colon cancer. Experimental Design: The impact of TP53 genotype was prospectively evaluated in Cancer and Leukemia Group B 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL). Results: TP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease-free survival (DFS) or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type versus zinc- or non-zinc-binding mutations in the TP53 DNA-binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc- or non-zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men. Conclusions: The presence of any TP53 mutation within the DNA-binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men.

AB - Purpose: The TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA-binding domain of TP53 are associated with survival in stage III colon cancer. Experimental Design: The impact of TP53 genotype was prospectively evaluated in Cancer and Leukemia Group B 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL). Results: TP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease-free survival (DFS) or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type versus zinc- or non-zinc-binding mutations in the TP53 DNA-binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc- or non-zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men. Conclusions: The presence of any TP53 mutation within the DNA-binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men.

UR - http://www.scopus.com/inward/record.url?scp=84886407775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886407775&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-13-0351

DO - 10.1158/1078-0432.CCR-13-0351

M3 - Article

VL - 19

SP - 5777

EP - 5787

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 20

ER -