Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma.

George João Ferreira do NASCIMENTO,Silvia Regina Batistuzzo de MEDEIROS,Roseana de Almeida FREITAS,Thayse Azevedo da SILVA,Felipe Rodrigues de MATOS,Leorik Pereira da SILVA,Lélia Batista de SOUZA

doi:10.1590/1807-3107bor-2021.vol35.0019

Abstract

Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

Highlights

Oral squamous cell carcinoma (OSCC) is a significant health problem worldwide, representing more than 95% of primary malignant tumors of the oral cavity.[1]
Regarding the matrix metalloproteinase (MMPs)-7 -181G polymorphism, the G allele frequency associated with higher enzyme activity was significantly greater in oral tongue squamous cell carcinoma (OTSCC) cases, compared with the controls
Regarding the MMP-9 -1562T polymorphism, the T allele frequency was significantly greater in OTSCC cases, compared with the controls

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is a significant health problem worldwide, representing more than 95% of primary malignant tumors of the oral cavity.[1] The latest global estimates indicate that about 300,000 cases were diagnosed and 145,000 deaths occurred in 2012.2 The most commonly affected anatomic site is the tongue, and despite advances in treatment, the 5-year survival rate for this cancer has shown no significant improvement in the last decades, remaining between 50–55%.3. Efforts are being made to better understand certain differences in the molecular characteristics of neoplastic cells and the tumor microenvironment, aiming at discovering new diagnostic and therapeutic approaches. The extracellular matrix acts as a structural support network within the tissues, and as a barrier to cell migration.

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