Association of TP53 Mutational Status and Gender with Survival after Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803

• Published in: Clinical cancer research Vol. 19; no. 20; pp. 5777 - 5787
• Main Authors: WARREN, Robert S, ATREYA, Chloe E, SALTZ, Leonard B, BERTAGNOLLI, Monica M, NIEDZWIECKI, Donna, WEINBERG, Vivian K, DONNER, David B, MAYER, Robert J, GOLDBERG, Richard M, COMPTON, Carolyn C, ZURAEK, Marlene B, YE, Cynthia
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.10.2013
• Subjects: Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy, Adjuvant; Colonic Neoplasms - genetics; Colonic Neoplasms - mortality; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; DNA - chemistry; DNA - metabolism; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Humans; Male; Medical sciences; Microsatellite Instability; Models, Molecular; Molecular Conformation; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Neoplasm Staging; Pharmacology. Drug treatments; Protein Binding; Sex Factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Suppressor Protein p53 - chemistry; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Zinc - chemistry; Zinc - metabolism; Sex; Adjuvant treatment; Malignant tumor; Survival; Result; Colonic disease; Colon cancer; TP53 Gene; Digestive diseases; Intestinal disease; Genetics; Locally advanced stage; Mutation; Cancer; Tumor suppressor gene
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-13-0351

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. 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). 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. 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.