Combined Effect of HPV and Several Gene SNPs in Laryngeal Cancer

Medicina (Kaunas). 2020 Feb 17;56(2):81. doi: 10.3390/medicina56020081.

Abstract

Background and objectives: Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck tumors. The molecular mechanism of LSCC remains unclear. The aim of this study was to evaluate the prevalence of Human papillomavirus (HPV) and single nucleotide polymorphisms (SNPs) of TP53, MDM2, MDM4, MTHFR, CASP8, and CCR5 genes in LSCC, and to assess their correlations with patient survival. Materials and Methods: 49 LSCC patients were enrolled in this study. PCR and qRT-PCR were used to detect, identify, and quantify HPV. SNPs were genotyped using PCR and PCR-RFLP. Results: By analyzing the interactions of the SNPs of the genes with clinical parameters, the majority of patients with lymph node status (N1,2) were identified as carriers of MDM2 T/G, CASP8 ins/del, CCR5 wt/wt SNP. Cluster analysis showed that patients with MDM2 T/T SNP survive longer than patients identified as CASP8 ins/ins, MTHFR C/C, and MDM4 A/A variant carriers; meanwhile, LSCC patients with MDM2 T/T polymorphic variant had the best survival. Multivariate analysis showed that HPV-positive patients without metastasis in regional lymph nodes (N0) and harboring CASP8 ins/del variant had the best survival. Meanwhile, HPV-negative patients with identified metastasis in lymph nodes (N1 and N2) and CASP8 ins/del variant had poor survival. Conclusions: This finding suggests patients survival prognosis and tumor behavior are different according HPV status, SNP variants, and clinical characteristics of the LSCC.

Keywords: human papillomavirus; laryngeal squamous cell carcinoma; multivariate analysis; patient survival; single nucleotide polymorphisms.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Caspase 8 / analysis
  • Cell Cycle Proteins / analysis
  • Female
  • Humans
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / analysis
  • Middle Aged
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Prognosis
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins c-mdm2 / analysis
  • Receptors, CCR5 / analysis
  • Tumor Suppressor Protein p53 / analysis

Substances

  • CCR5 protein, human
  • Cell Cycle Proteins
  • MDM4 protein, human
  • Proto-Oncogene Proteins
  • Receptors, CCR5
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • CASP8 protein, human
  • Caspase 8