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

基质金属蛋白酶(MMPs)被认为参与了癌症发展的初期和进展期，以及癌症的侵袭性表型。本研究探讨了基质金属蛋白酶-1和基质金属蛋白酶-3启动子区域的单核苷酸多态与口腔鳞癌易感性的关系。我们比较了170例日本口腔鳞状细胞癌患者和164例健康对照的基质金属蛋白酶-1和基质金属蛋白酶-3的基因分型。口腔鳞癌患者中MMP12G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，年龄在45岁以上的受试者患口腔鳞癌的风险显著增加(2.47倍)(95%CI1.47-4.14，p=0.0006)，携带MMP一2G等位基因的受试者患口腔鳞癌的风险增加2.30倍(95%CI1.15-4.58，p=0.018)。本研究的关键发现之一是，在45岁以下的早发性口腔鳞癌患者中，MMP-11G/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，84.4%的病例以舌头为主要部位。这可能暗示了特定的致癌机制，即特定的致癌刺激和/或舌头中的遗传因素。由于在一般人群中，2G等位基因是主要的MMP1基因，因此MMP12G等位基因的作用被认为是遗传背景，但本报告为MMP12G等位基因在早发性口腔鳞癌中的关键作用提供了证据。

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.