The 2G allele of promoter region of Matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma

We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3.The frequency of the MMP-1 2G allele was higher and that of the 1G homozygote was lower in the OSCC cases (p = 0.034). A multivariate logistic regression analysis revealed that subjects who were 45 years old or older had a significantly increased (2.47-fold) risk of OSCC (95%CI 1.47–4.14, p = 0.0006), and those carrying the MMP-1 2G allele had a 2.30-fold risk (95%CI 1.15–4.58, p = 0.018), indicating independent involvement of these factors in OSCC. One of the key discoveries of this research is the apparent reduction of the MMP-1 1G/1G and 1G/2G genotype distributions among the early onset OSCC cases under the ages of 45 years. It should be noted that the tongue was the primary site in 86.2% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue.Since the 2G allele is a majority of the MMP-1 genotype in the general population, it seems to act as a genetic pre-condition in OSCC development. However this report suggests a crucial impact of the MMP-1 2G allele in the early onset OSCC.Matrix metalloproteinase (MMP)-1 (Collagenase-1) is a major proteinase of the MMP family that specifically degrades type I collagen, which is a major component of the extracellular matrix (ECM), as well as other fibrillar collagens of types II, III, V and IX [1,2]. MMP-3 (Stromelysine-1) is responsible for degradation of type IV collagen, which forms the basement membrane, and collagen V, IX, X [3]. MMP-3 also has a role in activation of proMMP-1 in tumor tissue into the active form of MMP-1 [4]. Gene expression data in our previous report demonstrated enhanced expression of MMP family genes in OSCC tissues, and suggested correlation of high expression levels of MMP-1 and MMP-3 with aggressive behavior, such as metastasis, and clinical prognosis [5]. Similar correlations have been reported i