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

Abstract

BackgroundMatrix metalloproteinase (MMP) is known to be involved in the initial and progressive stages of cancer development, and in the aggressive phenotypes of cancer. This study examines the association of single nucleotide polymorphisms in promoter regions of MMP-1 and MMP-3 with susceptibility to oral squamous cell carcinoma (OSCC).MethodsWe compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3.ResultsThe 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.ConclusionSince 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.

Clinical significance of a single nucleotide polymorphism and allelic imbalance of matrix metalloproteinase-1 promoter region in prostate cancer

“…Recent epidemiological studies have demonstrated almost consistent results regarding the biological function of the MMP-1 promoter polymorphism and its association with the susceptibility or progression in several cancer types (4,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The 2G allele of the polymorphism has been reported to be related with increased risk of colorectal, lung, endometrial, ovary, kidney, and bladder cancers (4,(12)(13)(14)(15)(16)(17)(18)(19)(20), while the 2G allele was associated with tumor progression or patient survival but not with susceptibility of uterus, stomach, and colorectal (24)(25)(26)(27).…”

“…The 2G allele of the polymorphism has been reported to be related with increased risk of colorectal, lung, endometrial, ovary, kidney, and bladder cancers (4,(12)(13)(14)(15)(16)(17)(18)(19)(20), while the 2G allele was associated with tumor progression or patient survival but not with susceptibility of uterus, stomach, and colorectal ONCOLOGY REPORTS 22: 493-499, 2009 …”

“…The 2G allele of the polymorphism has been reported to be related with increased risk of colorectal, lung, endometrial, ovary, kidney, and bladder cancers (4,(12)(13)(14)(15)(16)(17)(18)(19)(20), while the 2G allele was associated with tumor progression or patient survival but not with susceptibility of uterus, stomach, and colorectal (24)(25)(26)(27). Determining which of the polymorphic alleles is amplified and how the amplified allele affects the expression of MMP-1 or phenotypes of cancers is also of interest.…”

Biomarkers of aggressive pituitary adenomas

“…MMP1 expression has been linked to a poor prognosis in several cancers including oral carcinoma (Nishizawa et al 2007, Shimizu et al 2008, nasopharyngeal carcinoma (Nasr et al 2007), and colorectal cancer (Woo et al 2007). The MMP1 gene is located on chromosome 11q22 (Arakaki et al 2009).…”

Papel do polimorfismo genético na expressão das metaloproteases na tendinopatia primária do tendão tibial posterior

“…al., 2008), carcinoma oral (Shimizu et. al., 2008;Nishizawa et. al., 2007), carcinoma de nasofaringe (Nasr et.…”