BMC Cancer Research article BioMed Central Open Access The 2G allele of promoter region of Matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma Rishiho Nishizawa1, Masaki Nagata*2, Arhab A Noman2, Nobutaka Kitamura2, Hajime Fujita2, Hideyuki Hoshina2, Takehiko Kubota3, Manami Itagaki3, Susumu Shingaki4, Makoto Ohnishi5, Hiroshi Kurita1, Kouji Katsura6, Chikara Saito4, Hiromasa Yoshie3 and Ritsuo Takagi2 Address: 1Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan, 2Division of Oral and Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental Sciences, Gakkocho-dori 2-5274, Niigata 951-8514, Japan, 3Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Gakkocho-dori 2-5274, Niigata 951- 8514, Japan, 4Division of Reconstructive Surgery for Oral and Maxillofacial Region, Niigata University Graduate School of Medical and Dental Sciences, Gakkocho-dori 2-5274, Niigata 951-8514, Japan, 5Division of Dental Clinic and Oral Surgery, Nagaoka Red Cross Hospital, Terashimamachi 297-1, Nagaoka 940-2085, Japan and 6Division of Oral and Maxillofacial Radiology, Niigata University Graduate School of Medical and Dental Sciences, Gakkocho-dori 2-5274, Niigata 951-8514, Japan Email: Rishiho Nishizawa - ni4zawa@hsp.md.shinshu-u.ac.jp; Masaki Nagata* - nagata@dent.niigata-u.ac.jp; Arhab A Noman - arhabn@dent.niigata-u.ac.jp; Nobutaka Kitamura - nktmr@m12.alpha-net.ne.jp; Hajime Fujita - fujita1@dent.niigata-u.ac.jp; Hideyuki Hoshina - hoshina@dent.niigata-u.ac.jp; Takehiko Kubota - kubota@dent.niigata-u.ac.jp; Manami Itagaki - ita@dent.niigata-u.ac.jp; Susumu Shingaki - shigaki@dent.niigata-u.ac.jp; Makoto Ohnishi - namakoto@dent.niigata-u.ac.jp; Hiroshi Kurita - hkurita@hsp.md.shinshu- u.ac.jp; Kouji Katsura - katsu@dent.niigata-u.ac.jp; Chikara Saito - ckrsaito@dent.niigata-u.ac.jp; Hiromasa Yoshie - yoshie@dent.niigata- u.ac.jp; Ritsuo Takagi - takagi@dent.niigata-u.ac.jp * Corresponding author Published: 5 October 2007 BMC Cancer 2007, 7:187 doi:10.1186/1471-2407-7-187 This article is available from: http://www.biomedcentral.com/1471-2407/7/187 Received: 19 March 2007 Accepted: 5 October 2007 © 2007 Nishizawa et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. Page 1 of 9 (page number not for citation purposes)