title: 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: 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.
authors.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
authors.forename: Rishiho
authors.initials: R
authors.lastname: Nishizawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagata
authors.forename: Arhab A
authors.initials: AA
authors.lastname: Noman
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kitamura
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujita
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hoshina
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kubota
authors.forename: Manami
authors.initials: M
authors.lastname: Itagaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Shingaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurita
authors.forename: Kouji
authors.initials: K
authors.lastname: Katsura
authors.forename: Chikara
authors.initials: C
authors.lastname: Saito
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yoshie
authors.forename: Ritsuo
authors.initials: R
authors.lastname: Takagi
mesh_terms: 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
chemical_list: D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1