González-Arriaga Patricia, López-Cima M Felicitas, Fernández-Somoano Ana, Pascual Teresa, Marrón Manuel G, Puente Xose S, Tardón Adonina
Departamento de Medicina, Unidad de Epidemiología Molecular del Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
BMC Cancer. 2008 Dec 19;8:378. doi: 10.1186/1471-2407-8-378.
Matrix metalloproteases (MMPs) constitute a family of enzymes capable of degrading different components of the extracellular matrix and are implicated in the invasion of tumor cells through the basement membrane. Polymorphisms in MMP genes may result in changes in the expression of MMPs being associated with the development and progression of cancer. We have investigated the association between three polymorphisms (-1607 1G/2G, +17 C/G and -77 A/G) in the human collagenases MMP1, MMP8 and MMP13 and the risk of development or progression of lung cancer.
A hospital-based case-control study was designed including 501 lung cancer patients and 510 controls matched. Genotypes were determined by PCR-RFLP. Results were analyzed using unconditional logistic regression, Cox's proportional hazard regression, and the Kaplan-Meier method.
The MMP1 and MMP13 promoter polymorphisms were not associated with lung cancer risk, while the C/G polymorphism in MMP8 was associated with a statistically significant decreased risk of developing lung cancer (ORadj = 0.65; 95%CI = 0.45-0.93). The Kaplan-Meier analysis showed that the polymorphisms in MMP1, MMP8 and MMP13 not seem to modify the overall survival. Multivariate analysis revealed that MMP1, MMP8 and MMP13 polymorphisms are not independent prognostic factors for overall survival.
This study suggests that the polymorphism in MMP8 is associated with a decreased lung cancer risk, which can be used as a prognostic marker in lung cancer.
基质金属蛋白酶（MMPs）是一类能够降解细胞外基质不同成分的酶，与肿瘤细胞通过基底膜的侵袭有关。MMP基因的多态性可能导致MMPs表达的变化，这与癌症的发生和发展有关。我们研究了人类胶原酶MMP1、MMP8和MMP13中的三种多态性（-1607 1G/2G、+17 C/G和-77 A/G）与肺癌发生或进展风险之间的关联。
设计了一项基于医院的病例对照研究，纳入501例肺癌患者和510例匹配的对照。通过PCR-RFLP确定基因型。使用无条件逻辑回归、Cox比例风险回归和Kaplan-Meier方法分析结果。
MMP1和MMP13启动子多态性与肺癌风险无关，而MMP8中的C/G多态性与肺癌发生风险显著降低相关（校正OR = 0.65；95%CI = 0.45 - 0.93）。Kaplan-Meier分析表明，MMP1、MMP8和MMP13的多态性似乎不会改变总生存期。多变量分析显示，MMP1、MMP8和MMP13多态性不是总生存期的独立预后因素。
本研究表明，MMP8多态性与肺癌风险降低相关，可作为肺癌的预后标志物。
