title: Association of p53 codon 72 genotypes and clinical outcome in human papillomavirus-infected lung cancer patients.
abstract: BACKGROUND
  We recently reported that high-risk human papillomavirus (HPV) 16/18 E6 protein was associated with p53 protein degradation in lung cancer. The present study addressed the relationship between the different p53 genotypes and HPV oncoprotein expression with respect to p53 protein degradation and clinical outcome in primary lung cancer patients.
  
  
  METHODS
  We examined whether p53 codon 72 polymorphism and HPV oncoprotein expression could be associated with patients' outcome by collecting 319 lung tumors from patients with non-small cell lung cancer to determine p53 codon 72 polymorphisms, HPV 16/18 infection, and HPV 16/18 E6 and p53 protein expression by polymerase chain reaction (PCR)-restriction fragment length polymorphism, nested-PCR, and immunohistochemical analysis.
  
  
  RESULTS
  The presence of HPV 16/18 DNA and E6 protein was inversely associated with p53 expression. The frequency of p53 protein degradation was also much higher in HPV 16/18 E6-positive/Arg/Arg lung tumors than in the other 3 groups. After adjusting gender and tumor type, the major contributors to p53 degradation in lung cancer patients were determined to be p53 codon72 polymorphism and HPV 16/18 E6 oncoprotein expression. This association was not found for HPV 16/18 DNA infection. Survival was significantly longer in patients with HPV 16/18 E6-negative/Arg/Arg tumors (median 32.7 months) than in patients with HPV-positive and p53 genetic variant tumors (p=0.008).
  
  
  CONCLUSIONS
  The HPV 16/18 E6 protein, which is involved in the p53 inactivation that contributes to HPV-infected lung tumorigenesis, is associated with the p53 codon 72 genotype. The combination of HPV 16/18 E6 status and p53 codon72 polymorphism in lung tumors is an important biologic and prognostic parameter.
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, and Department of Thoracic Surgery, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Shih-Pin
authors.initials: SP
authors.lastname: Chen
authors.forename: Nan-Yung
authors.initials: NY
authors.lastname: Hsu
authors.forename: Jeng-Yuan
authors.initials: JY
authors.lastname: Wu
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chou
authors.forename: Huei
authors.initials: H
authors.lastname: Lee
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics*; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000235:genetics* / Q000821:virology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014412:Tumor Virus Infections / Q000235:genetics* / Q000821:virology
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D011505:Protein-Tyrosine Kinases