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


CONCLUSIONS
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.
Nishizawa
Rishiho
R
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
Nagata
Masaki
M
Noman
Arhab A
AA
Kitamura
Nobutaka
N
Fujita
Hajime
H
Hoshina
Hideyuki
H
Kubota
Takehiko
T
Itagaki
Manami
M
Shingaki
Susumu
S
Ohnishi
Makoto
M
Kurita
Hiroshi
H
Katsura
Kouji
K
Saito
Chikara
C
Yoshie
Hiromasa
H
Takagi
Ritsuo
R
D000328:Adult; D000368:Aged; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1