Combined Effect of HPV and Several Gene SNPs in Laryngeal Cancer.

Aušra Stumbrytė-Kaminskienė,Daiva Dabkevičienė,Irina Mackevičienė,Živilė Gudlevičienė

doi:10.3390/medicina56020081

Aušra Stumbrytė-Kaminskienė, Daiva Dabkevičienė + Show 2 more

Open Access

https://doi.org/10.3390/medicina56020081

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Journal: Medicina (Kaunas, Lithuania)	Publication Date: Feb 17, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: National Cancer Institute

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.

Highlights

A common malignancy found in the head and neck tumor is laryngeal squamous cell carcinoma (LSCC) [1,2], with 151,000 new cases diagnosed worldwide [3] each year and 90,000 associated deaths [4,5]
From rezults of the study we evaluated that 90 subjects are required to achieve 0.8 power as calculated hazard ratio is 0.36 and proportion of subjects died of the disease is 0.47
We found that polymorphic variants of the MDM2 gene G/G (4 out of 28, 18.8%) and Methylenetetrahydrofolate reductase (MTHFR) gene T/T (4 out of 21, 19.1%)) were more common in the samples of Human papillomavirus (HPV)-positive and HPV-negative patients

Summary

Introduction

A common malignancy found in the head and neck tumor is laryngeal squamous cell carcinoma (LSCC) [1,2], with 151,000 new cases diagnosed worldwide [3] each year and 90,000 associated deaths [4,5]. Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck tumors. 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. Multivariate analysis showed that HPV-positive patients without metastasis in regional lymph nodes (N0) and harboring CASP8 ins/del variant had the best survival. 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

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