2G allile of MMP-1 gene polymorphism increases risk of oral cancer

MMP-1基因2G等位基因多态性增加口腔癌风险

• 批准号: 18592171
• 负责人: HOSHINA Hideyuki
• 金额: $ 2.55万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592171/
• 关键词: Integrin; Tetraspanin; Biomarker; Cervical lymph node metastasis; Distant metastasis; Outcome; Oral squamous ell carcinoma

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). We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3. The frequency of the MMP-12G 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-11G/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 84.4% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue. Since the 2G allele is a majority of the MMP-1 genotype in the general population, the effect of MMP-12G allele was thought to act as a genetic background However this report provides evidence for the critical impact of the MMP-12G allele in the early onset OSCC.

已知基质金属蛋白酶（MMP）参与癌症发展的初始和进展阶段，以及癌症的侵袭性表型。本研究探讨了MMP-1和MMP-3启动子区域的单核苷酸多态性与口腔鳞状细胞癌（OSCC）易感性的关系。我们比较了170例日本OSCC病例和164名健康对照者的MMP-1和MMP-3基因型。OSCC病例中MMP-12G等位基因频率较高，1G纯合子频率较低（p=0.034）。多因素logistic回归分析显示，45岁及以上的受试者患OSCC的风险显著增加（2.47倍）（95%CI 1.47 ~ 4.14, p=0.0006），携带MMP-1 2G等位基因的受试者患OSCC的风险显著增加（2.30倍）（95%CI 1.15 ~ 4.58, p=0.018），表明这些因素独立参与OSCC。本研究的主要发现之一是在45岁以下早发性OSCC病例中，MMP-11G/1G和1G/2G基因型分布明显减少。值得注意的是，在这些早发病例中，舌头是84.4%的原发部位。这可能暗示了特定的致癌机制，即舌头中特定的致癌刺激和/或遗传因素。由于2G等位基因在普通人群中占MMP-1基因型的大多数，因此MMP-12G等位基因的作用被认为是遗传背景。然而，本报告为MMP-12G等位基因在早发性OSCC中的关键作用提供了证据。

项目成果

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

• DOI: 10.1186/1471-2407-7-187
• 发表时间: 2007-10-05
• 期刊: BMC CANCER
• 影响因子: 3.8
• 作者: Nishizawa, Rishiho;Nagata, Masaki;Noman, Arhab A.;Kitamura, Nobutaka;Fujita, Hajime;Hoshina, Hideyuki;Kubota, Takehiko;Itagaki, Manami;Shingaki, Susumu;Ohnishi, Makoto;Kurita, Hiroshi;Katsura, Kouji;Saito, Chikara;Yoshie, Hiromasa;Takagi, Ritsuo
• 通讯作者: Takagi, Ritsuo