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

已知基质金属蛋白酶（MMP）参与癌症发展的初始和进行性阶段，以及癌症的侵袭性表型。本研究旨在探讨MMP-1和MMP-3基因启动子区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患者和164例健康对照者的MMP-1和MMP-3基因型。MMP-12 G等位基因在口腔鳞癌中的频率较高，而1G纯合子的频率较低（p=0.034）。多变量logistic回归分析显示，45岁或以上的受试者的（2.47倍）OSCC风险（95%CI 1.47-4.14，p=0.0006），携带MMP-1 2G等位基因的患者有2.30倍的风险（95%CI 1.15-4.58，p=0.018），表明这些因素独立参与OSCC。本研究的关键发现之一是45岁以下的早发性OSCC病例中MMP-11 G/1G和1G/2G基因型分布明显减少。应该指出的是，在这些早发病例中，舌是84.4%的原发部位。这可能表明特定的致癌机制，即舌头中特定的致癌刺激和/或遗传因素。由于2G等位基因在一般人群中占MMP-1基因型的大多数，因此MMP-12 G等位基因的作用被认为是遗传背景。然而，本报告为MMP-12 G等位基因在早发性OSCC中的关键影响提供了证据。

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.