Vairaktaris Eleftherios, Yapijakis Christos, Vasiliou Stavros, Derka Spyridoula, Nkenke Emeka, Serefoglou Zoe, Vorris Eleni, Vylliotis Antonis, Ragos Vasilios, Neukam Friedrich W, Patsouris Efstratios
Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Vas. Sofias 93 and Dim. Soutsou 1, Athens 11521, Greece.
Anticancer Res. 2007 Nov-Dec;27(6B):4095-100.
Matrix metalloproteinase-3 (MMP-3) plays a pivotal role in inflammation and thrombosis. Increased levels of MMP-3 have been correlated with progression of oncogenesis and metastasis. Inflammation-related factors have recently been found to contribute to the development of malignancies. The present study investigated the possible association of -1171 5A/6A polymorphism, which influences expression of MMP-3, with risk for oral cancer.
This polymorphism was examined by restriction enzyme analysis in 160 patients with oral squamous cell carcinoma (OSCC) and 156 healthy controls of equivalent gender, age and ethnicity (Greeks and Germans).
A significant increase of 5A/6A heterozygotes was observed in the whole group and several subgroups of patients compared to controls (p < 0.05). Nevertheless, in these subgroups and the whole patient group, the 5A allele and carrier frequencies did not differ significantly from those of the control group. The only significant increase of 5A allele-related frequencies (p < 0.05) in comparison with controls was observed in subgroups of patients with a positive family history of cancer (5A allele carrier frequency only), with advanced stages of cancer (5A allele frequency only) and without positive history of thrombophilia (both 5A allele and carrier frequencies). In addition, the genotypes containing the 5A allele (5A/5A and 5A/6A) had a double risk of OSSC development in smokers (odds ratio (OR) 2.16, 95% confidence interval (CI) 1.04-4.48 and OR 1.78, 95% CI 1.01-3.13, respectively).
The results of this study suggest that the high expression 5A allele of the MMP-3 gene is associated with an increased risk for oral cancer in certain individuals.
基质金属蛋白酶-3（MMP-3）在炎症和血栓形成中起关键作用。MMP-3水平升高与肿瘤发生和转移的进展相关。最近发现炎症相关因子有助于恶性肿瘤的发展。本研究调查了影响MMP-3表达的-1171 5A/6A多态性与口腔癌风险之间的可能关联。
通过限制性酶切分析检测了160例口腔鳞状细胞癌（OSCC）患者和156例年龄、性别和种族（希腊人和德国人）匹配的健康对照者的这种多态性。
与对照组相比，在整个患者组和几个亚组中观察到5A/6A杂合子显著增加（p < 0.05）。然而，在这些亚组和整个患者组中，5A等位基因和携带者频率与对照组相比无显著差异。与对照组相比，仅在有癌症家族史的患者亚组（仅5A等位基因携带者频率）、癌症晚期患者亚组（仅5A等位基因频率）和无血栓形成阳性史的患者亚组（5A等位基因和携带者频率）中观察到5A等位基因相关频率显著增加（p < 0.05）。此外，含有5A等位基因的基因型（5A/5A和5A/6A）在吸烟者中发生OSCC的风险加倍（优势比（OR）分别为2.16，95%置信区间（CI）1.04 - 4.48和OR 1.78，95%CI 1.01 - 3.13）。
本研究结果表明，MMP-3基因的高表达5A等位基因与某些个体患口腔癌的风险增加有关。
