title: Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  The cooperation between phorbol 12-myristate 13-acetate induced protein 1 (NOXA) and myeloid cell leukemia 1 (MCL1) is critical in the intrinsic apoptotic pathway. Human papillomavirus 16 (HPV16), by inducing p53 and pRb-E2F degradation, may play an essential role in development of squamous cell carcinoma of the head and neck (SCCHN) through NOXA-MCL1 axis-mediated apoptosis. Therefore, genetic variants of NOXA and MCL1 may modify the SCCHN risk associated with HPV16 seropositivity.
  
  
  METHODS
  HPV16 serology was obtained by immunoadsorption assay. Four functional SNPs in the promoter of NOXA (rs9957673, rs4558496) and MCL1 (rs9803935, rs3738485) were genotyped for 380 cases and 335 frequency-matched cancer-free controls of non-Hispanic whites.
  
  
  RESULTS
  Associations between the four polymorphisms and SCCHN risk were not significant, while we observed a significantly joint effect on SCCHN risk between the polymorphisms and HPV16 seropositivity. Notably, this effect modification was particularly pronounced for oropharyngeal cancer in subgroups including never smokers, never drinkers and younger subjects.
  
  
  CONCLUSIONS
  Our results suggested that polymorphisms of NOXA and MCL1 may modify the risk of HPV16-associated oropharyngeal cancer. The further identification of population subgroups at higher risk provides evidence that HPV-targeting treatment may help benefit SCCHN. However, larger studies are needed to validate our findings.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
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; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000821:virology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D030361:Papillomavirus Infections / Q000150:complications*; D020641:Polymorphism, Single Nucleotide; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012306:Risk; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult
chemical_list: D064549:Myeloid Cell Leukemia Sequence 1 Protein; C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2