title: Polymorphisms of MDM4 and risk of squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  Mouse double minute 4 (MDM4), a homolog of MDM2, is one of the key negative regulators of p53, and its amplification or overexpression contributes to carcinogenesis by inhibiting the p53 tumor suppressor activity. We investigated the association between MDM4 polymorphisms and the risk of squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  We genotyped three MDM4 tagging polymorphisms, two in the 3' untranslated region (rs11801299G>A and rs10900598G>T) and one in intron 1 (rs1380576C>G), in a case-control study of 1075 non-Hispanic white SCCHN patients and 1079 cancer-free controls, and evaluated their associations with SCCHN risk.
  
  
  RESULTS
  Although none of these three polymorphisms individually had a statistically significant effect on the risk of SCCHN, nor did their combined number of putative risk genotypes (i.e. rs11801299GG, rs1380576CG+GG, and rs10900598GG) [odds ratio (OR)=1.16; 95% confidence interval (95% CI) =0.93-1.45], we found that individuals with 1-3 risk genotypes had statistically significant increased risk of oropharyngeal cancer (OR=1.32; 95% CI=1.00-1.73), particularly for those with T1-2 stage (OR=1.40; 95% CI=1.02-1.94), those with regional lymph node metastases (N1-3) (OR=1.44; 95% CI=1.07-1.95), and those with late stages (III and IV) (OR=1.34; 95% CI=1.01-1.77).
  
  
  CONCLUSIONS
  These results suggest that the joint effect of MDM4 variants may contribute to the risk of oropharyngeal cancer in non-Hispanic whites. Additional studies are warranted to unravel whether the particular stage distribution of oropharyngeal cancer with the strongest association (T1-2, N1-3, and III-IV) is a possible link with human papillomavirus-related oropharyngeal cancers.
authors.affiliation: Departments of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Hongping
authors.initials: H
authors.lastname: Yu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D005260:Female; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking; D000077195:Squamous Cell Carcinoma of Head and Neck; D013781:Texas / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins