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

Nishizawa R, Nagata M, Noman AA, Kitamura N, Fujita H, Hoshina H, Kubota T, Itagaki M, Shingaki S, Ohnishi M, Kurita H, Katsura K, Saito C, Yoshie H, Takagi R - BMC Cancer (2007)

Bottom Line: 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.This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue.However this report suggests a crucial impact of the MMP-1 2G allele in the early onset OSCC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan. ni4zawa@hsp.md.shinshu-u.ac.jp

ABSTRACT

Background: Matrix 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).

Methods: We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3.

Results: 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.

Conclusion: 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.

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Related in: MedlinePlus

Age distribution of the MMP-1 genotypes in 170 OSCC cases between the ages of 20 and 80 years. The frequency of the 1G/1G genotype is notably low. Note the clear reduction of the 1G/1G and 1G/2G genotype distributions in individuals under the ages of 45 and 35 years, respectively.
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Figure 1: Age distribution of the MMP-1 genotypes in 170 OSCC cases between the ages of 20 and 80 years. The frequency of the 1G/1G genotype is notably low. Note the clear reduction of the 1G/1G and 1G/2G genotype distributions in individuals under the ages of 45 and 35 years, respectively.

Mentions: MMP-1 promoter genotypes of OSCC cases were stratified by clinical parameters including gender, age (Table 2), T category, lymph-node metastasis (N category), tumor location in the oral cavity, status of alcohol intake and smoking (Table 3). A significant association was detected only between the age and MMP-1 genotype, which suggests accumulation of older age patients with the 1G allele, or young age patients with the 2G allele. Figure 1 shows the age distribution pattern of subjects with MMP-1 promoter genotypes in OSCC groups, demonstrating a remarkable reduction of the 1G/1G and 1G/2G genotype distributions in OSCC cases less than 45 years and 35 years old. Receiver operating characteristic (ROC) curve consistently exhibited that the 45 years of age could be an optimal cutoff value of the age at which to stratify the young OSCC from the older bracket in following analyses. It was of considerable interest to notice that the MMP-1 promoter genotype has a remarkable difference in distribution between subjects over and under 45 years of age. A significant difference was demonstrated in susceptibility to OSCC in individuals less or more than 45 years old (p = 0.002, OR = 2.26, 95%CI = 1.35–3.79) (Table 4). No association was observed with the 1G allele (1G/1G and 1G/2G; p = 0.294, OR = 1.29, 95%CI = 0.84–2.00, whereas a significantly elevated risk of OSCC was exhibited with the 2G allele (2G/2G and 1G/2G; p = 0.016, OR = 2.39, 95%CI = 1.21–4.72. The environmental factors, alcohol intake and smoking status were stratified with MMP-1 genotype distributions in OSCC cases, but no significant association was demonstrated of either factor with the MMP-1 genotype distribution (Table 3).


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

Nishizawa R, Nagata M, Noman AA, Kitamura N, Fujita H, Hoshina H, Kubota T, Itagaki M, Shingaki S, Ohnishi M, Kurita H, Katsura K, Saito C, Yoshie H, Takagi R - BMC Cancer (2007)

Age distribution of the MMP-1 genotypes in 170 OSCC cases between the ages of 20 and 80 years. The frequency of the 1G/1G genotype is notably low. Note the clear reduction of the 1G/1G and 1G/2G genotype distributions in individuals under the ages of 45 and 35 years, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2089080&req=5

Figure 1: Age distribution of the MMP-1 genotypes in 170 OSCC cases between the ages of 20 and 80 years. The frequency of the 1G/1G genotype is notably low. Note the clear reduction of the 1G/1G and 1G/2G genotype distributions in individuals under the ages of 45 and 35 years, respectively.
Mentions: MMP-1 promoter genotypes of OSCC cases were stratified by clinical parameters including gender, age (Table 2), T category, lymph-node metastasis (N category), tumor location in the oral cavity, status of alcohol intake and smoking (Table 3). A significant association was detected only between the age and MMP-1 genotype, which suggests accumulation of older age patients with the 1G allele, or young age patients with the 2G allele. Figure 1 shows the age distribution pattern of subjects with MMP-1 promoter genotypes in OSCC groups, demonstrating a remarkable reduction of the 1G/1G and 1G/2G genotype distributions in OSCC cases less than 45 years and 35 years old. Receiver operating characteristic (ROC) curve consistently exhibited that the 45 years of age could be an optimal cutoff value of the age at which to stratify the young OSCC from the older bracket in following analyses. It was of considerable interest to notice that the MMP-1 promoter genotype has a remarkable difference in distribution between subjects over and under 45 years of age. A significant difference was demonstrated in susceptibility to OSCC in individuals less or more than 45 years old (p = 0.002, OR = 2.26, 95%CI = 1.35–3.79) (Table 4). No association was observed with the 1G allele (1G/1G and 1G/2G; p = 0.294, OR = 1.29, 95%CI = 0.84–2.00, whereas a significantly elevated risk of OSCC was exhibited with the 2G allele (2G/2G and 1G/2G; p = 0.016, OR = 2.39, 95%CI = 1.21–4.72. The environmental factors, alcohol intake and smoking status were stratified with MMP-1 genotype distributions in OSCC cases, but no significant association was demonstrated of either factor with the MMP-1 genotype distribution (Table 3).

Bottom Line: 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.This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue.However this report suggests a crucial impact of the MMP-1 2G allele in the early onset OSCC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan. ni4zawa@hsp.md.shinshu-u.ac.jp

ABSTRACT

Background: Matrix 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).

Methods: We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3.

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus