Dept of Epigenomics and Cancer Risk Factors, German Cancer Research Center Heidelberg, Germany.
Eur Respir J. 2010 Feb;35(2):381-90. doi: 10.1183/09031936.00125608. Epub 2009 Jul 30.
The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) were investigated. For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS). The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage- and treatment-specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods. None of the investigated polymorphisms modified response significantly in the whole patient population. However, tumour stage IIIB variant allele carriers of MMP2 C-735T showed a significantly worse response. PFS was significantly prolonged in MMP1 G-1607GG variant allele carriers and OS in small cell lung cancer patients carrying the MMP12 A-82G variant allele. In conclusion, this study identified SNPs in MMP1, MMP2, MMP7 and MMP12 for further investigation as possible predictors of chemotherapy outcome in lung cancer patients.
接受化疗的肺癌患者预后较差。基质金属蛋白酶（MMP）基因中的单核苷酸多态性（SNP）可能通过改变凋亡途径影响治疗效果。研究了六个基因（MMP1、MMP2、MMP3、MMP7、MMP9 和 MMP12）中 8 个具有已知或疑似表型效应的 SNP。对 349 名接受一线化疗的原发性肺癌白种人患者，分析了三个不同的终点：第二周期后的反应、无进展生存期（PFS）和总生存期（OS）。使用多因素逻辑回归分析所有患者以及组织学、分期和治疗特异性亚组的 SNP 的预后价值。使用 Cox 回归方法计算 PFS 和 OS 的风险比估计值。在整个患者人群中，未发现所研究的多态性明显改变反应。然而，MMP2 C-735T 肿瘤分期 IIIB 变体等位基因携带者的反应明显较差。MMP1 G-1607GG 变体等位基因携带者的 PFS 显著延长，携带 MMP12 A-82G 变体等位基因的小细胞肺癌患者的 OS 也显著延长。总之，这项研究确定了 MMP1、MMP2、MMP7 和 MMP12 中的 SNP 作为进一步研究的可能预测因子，以评估肺癌患者化疗的效果。
