title: MicroRNA variants increase the risk of HPV-associated squamous cell carcinoma of the oropharynx in never smokers.
abstract: BACKGROUND
  Both microRNAs and human papillomavirus (HPV) infection play an important role in the development and progression of oral squamous cell carcinoma (OSCC). In addition, microRNAs affect all facets of the immune/inflammation responses to infection, which may control HPV clearance. We thus hypothesized that microRNA polymorphisms modify the association between HPV16 seropositivity and OSCC risk.
  
  
  METHODS
  Four single-nucleotide polymorphisms in microRNAs were genotyped and HPV16 serology was determined in 325 cases and 335 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariable logistic regression models.
  
  
  RESULTS
  Overall, each polymorphism had no significant main effect on OSCC risk. Compared with the risk among individuals with both miR146 rs2910164 GG genotype and HPV16 seronegativity, risk of OSCC was increased among those with CG or CC genotype and HPV16 seronegativity (OR, 1.2; 95% CI, 0.9-1.8), GG genotype and HPV16 seropositivity (OR, 3.0; 95% CI, 1.8-5.0), and CG or CC genotype and HPV16 seropositivity (OR, 4.7; 95% CI, 2.3-9.4). Similar results were found for miR149 rs2292832, miR196 rs11614913, and miR499 rs3746444. Analyses stratified by tumor sites and smoking status showed that each polymorphism significantly increased the risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly prominent in never smokers.
  
  
  CONCLUSIONS
  Our results indicate that microRNA polymorphisms modify the risk of OSCC associated with HPV16 seropositivity, particularly in patients with SCCOP and never smokers. Larger studies are needed to verify our findings.
authors: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Xicheng
authors: X
authors: Song
authors: Erich M
authors: EM
authors: Sturgis
authors: Jun
authors: J
authors: Liu
authors: Lei
authors: L
authors: Jin
authors: Zhongqiu
authors: Z
authors: Wang
authors: Caiyun
authors: C
authors: Zhang
authors: Qingyi
authors: Q
authors: Wei
authors: Guojun
authors: G
authors: Li
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000821:virology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000821:virology*; D020641:Polymorphism, Single Nucleotide; D012698:Serologic Tests; D012907:Smoking
chemical_list: D035683:MicroRNAs