title: Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC).
abstract: OBJECTIVE
  Though polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous tumors, particularly tumors associated with human papillomavirus (HPV) infection. However, the results remain controversial. Our previous study showed that HPV serostatus is not an independent risk factor for esophageal squamous cell carcinoma (ESCC) in nonsmokers and nondrinkers. Given the roles of p53 and HPV E6 as well as MDM2 oncoproteins in p53 degradation, we validated the association of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.
  
  
  METHODS
  Single nucleotide polymorphisms of p53 Arg72Pro (rs1042522) and MDM2 (rs937283) in 307 ESCC patients and 311 healthy controls were genotyped. The presence or absence of HPV16 in serum was measured by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to evaluate the possible associations of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.
  
  
  RESULTS
  Patients carrying p53 Arg/Arg or Arg/Pro had a higher risk of esophageal SCC (P<0.001, Odds ratio [OR] 4.98, 95% confidential interval [CI] 3.46-7.17), however, not found in MDM2 rs937283. The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity (P<0.001, OR 9.33, 95% CI 5.44-16.0), but not for MDM2 rs937283. The risk of esophageal SCC was further elevated among patients carrying Arg/Arg or Arg/Pro and HPV16-seropositivity who were smokers (P<0.001, OR 27.05, 95% CI 11.06-66.16) or drinkers (P<0.001, OR 13.20, 95% CI 5.74-30.38).
  
  
  CONCLUSIONS
  HPV16 seropositivity synergized with p53 Arg/Arg or Arg/Pro and increased ESCC risk, especially in smokers or drinkers.
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Huihua
authors.initials: H
authors.lastname: Xiong
authors.forename: Hong
authors.initials: H
authors.lastname: Qiu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Bei
authors.initials: B
authors.lastname: Chen
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Hu
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020022:Genetic Predisposition to Disease; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Drinking; ESCC; HPV; MDM2; Polymorphism; Smoking; p53