title: Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer: results of CALGB 89803.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Authors' Affiliations: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California; Department of Biostatistics and Bioinformatics, Alliance Statistics and Data Center, Duke University Medical Center, Durham, North Carolina; Dana-Farber Cancer Institute; Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts; The Ohio State University, Columbus, Ohio; National Cancer Institute, Bethesda, Maryland; and Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Robert S
authors: RS
authors: Warren
authors: Chloe E
authors: CE
authors: Atreya
authors: Donna
authors: D
authors: Niedzwiecki
authors: Vivian K
authors: VK
authors: Weinberg
authors: David B
authors: DB
authors: Donner
authors: Robert J
authors: RJ
authors: Mayer
authors: Richard M
authors: RM
authors: Goldberg
authors: Carolyn C
authors: CC
authors: Compton
authors: Marlene B
authors: MB
authors: Zuraek
authors: Cynthia
authors: C
authors: Ye
authors: Leonard B
authors: LB
authors: Saltz
authors: Monica M
authors: MM
authors: Bertagnolli
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D009367:Neoplasm Staging; D011485:Protein Binding; D012737:Sex Factors; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D004247:DNA; D015032:Zinc
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