Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer: results of CALGB 89803
| Autor: | Robert S. Warren, R. M. Goldberg, Leonard B. Saltz, Chloe E. Atreya, Monica M. Bertagnolli, Marlene B. Zuraek, David B. Donner, Robert J. Mayer, Carolyn C. Compton, Cynthia Ye, Vivian Weinberg, Donna Niedzwiecki |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Male Models Molecular Cancer Research medicine.medical_specialty Genotype Colorectal cancer medicine.medical_treatment Molecular Conformation Article Sex Factors Internal medicine Antineoplastic Combined Chemotherapy Protocols Adjuvant therapy Medicine Humans neoplasms Neoplasm Staging Chemotherapy business.industry Cancer DNA medicine.disease Irinotecan Leukemia Regimen Zinc Chemotherapy Adjuvant Immunology Colonic Neoplasms Mutation Female Microsatellite Instability Tumor Suppressor Protein p53 business medicine.drug Protein Binding |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 19(20) |
| ISSN: | 1557-3265 |
| Popis: | 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. Clin Cancer Res; 19(20); 5777–87. ©2013 AACR. |
| Databáze: | OpenAIRE |
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