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Abstract
BackgroundMatrix metalloproteinases (MMPs) are enzymes that degrade all the components of extra cellular matrix and collagen. Various types of MMPs are known to be expressed and activated in patients with oral submucous fibrosis (OSMF) as well as head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to asses the association of the single nucleotide polymorphism (SNP) adenosine insertion/deletion polymorphism (-1171 5A->6A) in the MMP-3 promoter region in these lesions.MethodsMMP-3 SNP was genotyped by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) analysis in a case control study consisting of 362 participants; 101 cases of OSMF, 135 of HNSCC and 126 controls, compared for age, sex and habits. ROC distribution was plotted to assess the contributions of genetic variation in MMP-3 genotypes with relation to age.ResultsAnalysis of MMP 3 (-1171 5A->6A) polymorphism revealed the frequency of 5A allele in OSMF, HNSCC and controls to be 0.15, 0.13 and 0.07, respectively. A significant difference was found in 5A genotype frequency between OSMF (5A genotype frequency = 0.15, p = 0.01, OR = 2.26, 95% CI = 1.22-4.20) and in controls (5A genotype frequency 0.07) as well as HNSCC (5A genotype frequency 0.13, p = 0.03,95%CI = 1.06-3.51) and controls (5A genotype frequency = 0.07) In this study, 5A genotype had greater than two fold risk for developing OSMF (OR = 2.26) and nearly the same in case of HNSCC (OR = 1.94) as compared to controls. In patients with OSMF as well as HNSCC, the ROC analysis between the MMP-3 genotype and age, 6A/6A allele was found to be significant in patients both over and under 45 years of age; while the 5A/5A carrier alleles showed an association only in patients less than 45 years of age.ConclusionsThis study concluded that the expression of MMP-3 genotype associated with the 5A alleles, it may have an important role in the susceptibility of the patients to develop OSMF and HNSCC.
Highlights
Matrix metalloproteinases (MMPs) are enzymes that degrade all the components of extra cellular matrix and collagen
MMP-3 promoter genotypes in patients with oral submucous fibrosis (OSMF), head and neck squamous cell carcinoma (HNSCC) and controls were analyzed with respect to gender, age, habits like tobacco consumption with or without areca nut chewing, alcohol intake, as well as histopathological grade of OSMF, TNM staging of HNSCC and the location of the lesion
Analyzing the different genotypes (6A/6A, 5A/6A and 5A/ 5A), it was found that the polymorphic association of these genotypes was statistically significant in both male and females suffering from OSMF (p = 0.001) and HNSCC (p = 0.01), according to the Fisher’s exact test
Summary
Matrix metalloproteinases (MMPs) are enzymes that degrade all the components of extra cellular matrix and collagen. Various types of MMPs are known to be expressed and activated in patients with oral submucous fibrosis (OSMF) as well as head and neck squamous cell carcinoma (HNSCC). The author’s group recently reviewed the molecular functions and single nucleotide polymorphic association of different MMPs such as MMP-1 (-1607 1G/ 2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C) and it’s possible therapeutic aspects of these proteases and they concluded that MMPs may play an association with potentially malignant (OSMF) and malignant head and neck lesions (HNSCC). MMP-3 transcription is higher in head and neck squamous cell carcinoma (HNSCC) and several other types of malignancies including lung and breast carcinomas [9,10,11,12]. MMP-3 can activate other MMPs, including collagenase, matrilysin and gelatinase B
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