title: p53 codon 72 polymorphisms in human papillomavirus-negative and human papillomavirus-positive squamous cell carcinomas of the oropharynx.
abstract: BACKGROUND
  Tobacco smoking, alcohol abuse, and high-risk human papillomavirus (HPV) are risk factors in the etiology of oropharyngeal squamous cell carcinomas (SCCs). The TP53 polymorphism, in which an arginine (R) is changed to proline (P) at codon 72, is functionally significant and could therefore be a predisposing genetic defect.
  
  
  METHODS
  The aim of the study was to investigate the role of codon 72 polymorphism by means of double gradient-denaturing gel electrophoresis in 77 oropharyngeal SCC patients including 33 TP53 mutated and 16 HPV-16-positive cases. The controls consisted of 141 consecutive healthy blood donors.
  
  
  RESULTS
  The cases and controls showed significantly different genotype distribution (P = .0005): the frequencies of the RR, RP, and PP genotypes among the cases were, respectively, 81.8%, 10.4%, and 7.8%, as opposed to 59.6%, 33.3%, and 7.1% among the controls, in agreement with the Hardy-Weinberg equilibrium (P = .35). The PP genotype was significantly overrepresented among females (22.2% vs 3.4%; P = .0243) and in HPV-16-positive cases (25.0% vs 3.3%; P = .0152). No segregation was found between either of the codon 72 genotypes and age or TP53 mutations.
  
  
  CONCLUSIONS
  The significantly lower frequency of the RP genotype in the patients as a whole suggests that it has a protective effect on oropharyngeal SCCs. Moreover, the PP genotype may be a risk factor for the development of oropharyngeal SCC by females and the development of HPV-16-related SCC, although the findings need to be validated in a larger number of tumors.
authors.affiliation: Unit of Experimental Molecular Pathology, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. federica.perrone@istitutotumori.mi.it
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Elisa
authors.initials: E
authors.lastname: Pastore
authors.forename: Marta
authors.initials: M
authors.lastname: Orsenigo
authors.forename: Simona
authors.initials: S
authors.lastname: Suardi
authors.forename: Barbara
authors.initials: B
authors.lastname: Marcomini
authors.forename: Luca
authors.initials: L
authors.lastname: DaRiva
authors.forename: Lisa
authors.initials: L
authors.lastname: Licitra
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D003062:Codon / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000821:virology; D030361:Papillomavirus Infections / Q000235:genetics*; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D003062:Codon; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53