title: Genetic variants of the p53 and p73 genes jointly increase risk of second primary malignancies in patients after index squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  Because of the structural and biochemical similarities between the antitumor p53 and p73 proteins, the authors hypothesized that individuals who carry high-risk genotypes of p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms have a higher risk of developing second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  A cohort of 1269 patients with index cases of SCCHN was recruited between May 1995 and January 2007 at The University of Texas MD Anderson Cancer Center and followed for SPM development. Patients were genotyped for p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms. A log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk among different risk groups with the combined risk genotypes of the 2 polymorphisms.
  
  
  RESULTS
  The data demonstrated that patients with p53 WP + PP and p73 GC/GC genotypes had a worse SPM-free survival and an increased SPM risk compared with the corresponding p53 WW and p73 GC/AT + AT/AT genotypes. After combining the 2 polymorphisms, a borderline significantly or significantly reduced SPM-free survival and increased SPM risk were observed in the medium-risk group (p53 WW and p73 GC/GC or p53 P carriers and p73 AT carriers) and high-risk group (p53 P carriers and p73 GC/GC) compared with low-risk group (p53 WW and p73 AT carriers), respectively.
  
  
  CONCLUSIONS
  The results suggest an increased risk of SPM after index SCCHN with both p53 and p73 polymorphisms individually and in combination.
authors: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Yang
authors: Y
authors: Zhang
authors: Erich M
authors: EM
authors: Sturgis
authors: Zhigang
authors: Z
authors: Huang
authors: Mark E
authors: ME
authors: Zafereo
authors: Qingyi
authors: Q
authors: Wei
authors: Guojun
authors: G
authors: Li
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics*; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D012307:Risk Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins