title: Association of tumor necrosis factor-alpha promoter variants with risk of HPV-associated oral squamous cell carcinoma.
abstract: BACKGROUND
  Tumor necrosis factor alpha (TNF-α) plays an important role in inflammation, immunity, and defense against infection and clearance of human papillomavirus (HPV). Thus, genetic variants may modulate individual susceptibility to HPV-associated oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  In this study we genotyped four common single nucleotide polymorphisms (SNPs) in the TNF-α promoter [ -308G > A(rs1800629), -857C > T (rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964)] and determined HPV16 serology in 325 OSCC cases and 335 matched controls and tumor HPV status in 176 squamous cell carcinomas of the oropharynx (SCCOP) patients. Univariate and multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
  
  
  RESULTS
  We found that HPV16 seropositivity alone was associated with an increased risk of OSCC (OR, 3.1; 95% CI, 2.1-4.6), and such risk of HPV16-associated OSCC was modified by each SNP. Patients with both HPV16 seropositivity and variant genotypes for each SNP had the highest risk when using patients with HPV16 seronegativity and a wild-type genotype as a comparison group. Moreover, similar results were observed for the combined risk genotypes of four variants and all such significant associations were more pronounced in several subgroups, particularly in SCCOP patients and never smokers. Notably, the combined risk genotypes of four variants were also significantly associated with tumor HPV-positive SCCOP.
  
  
  CONCLUSIONS
  Taken together, these results suggest that TNF-α SNPs may individually or, more likely, jointly affect individual susceptibility to HPV16-associated OSCC, particularly SCCOP and never smokers. Validation of our findings is warranted.
authors.affiliation: Department of Stomatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Huang
authors.forename: Xicheng
authors.initials: X
authors.lastname: Song
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D052162:Human papillomavirus 16; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha