Guangfu Jin and Ruifen Miao contributed equally to this work.
Putative functional polymorphisms of MMP9 predict survival of NSCLC in a Chinese population
Article first published online: 26 NOV 2008
Copyright © 2009 Wiley-Liss, Inc.
International Journal of Cancer
Volume 124, Issue 9, pages 2172–2178, 1 May 2009
How to Cite
Jin, G., Miao, R., Hu, Z., Xu, L., Huang, X., Chen, Y., Tian, T., Wei, Q., Boffetta, P. and Shen, H. (2009), Putative functional polymorphisms of MMP9 predict survival of NSCLC in a Chinese population. Int. J. Cancer, 124: 2172–2178. doi: 10.1002/ijc.24190
- Issue published online: 24 FEB 2009
- Article first published online: 26 NOV 2008
- Manuscript Accepted: 12 NOV 2008
- Manuscript Received: 4 SEP 2008
- National Outstanding Youth Science Foundation of China. Grant Number: 30425001
- Key Grant of National Natural Science Foundation of China. Grant Number: 30730080
- UICC Yamagiwa-Yoshida Memorial International Cancer Study Grant. Grant Number: YY1/08/017
- Jiangsu Society Development Foundation. Grant Number: BS2006005
Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and their over-expression is often associated with unfavorable survival of non-small cell lung cancer (NSCLC). Because genetic variants can alter expression level or biological activity of MMPs, we hypothesized that potentially functional single nucleotide polymorphisms (SNPs) in key MMP genes may be associated with the survival of NSCLC patients. We selected and genotyped 14 putative functional SNPs in six MMP genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) using PCR-RFLP methods in 561 NSCLC patients. Kaplan-Meier method with the log-rank test and Cox proportional hazard models were used for the survival analyses. The C-1562T, Arg279Gln and Arg668Gln polymorphisms in MMP9 were significantly associated with survival of patients with NSCLC (log-rank p values = 0.032, 0.038 and 0.036, respectively). The C-1562T and Arg668Gln loci were in complete linkage disequilibrium (r2 = 1). Patients carrying the 668Gln allele had improved survival with a median survival time (MST) of 51.6 months, compared with 21.8 months for those with the 668Arg/Arg genotype (log-rank p = 0.010). In contrast, the 279Gln/Gln genotype was associated with a significantly shortened MST (17.3 months, log-rank p = 0.030) in the recessive model. In the final multivariate Cox regression model, 279Gln/Gln was identified as an independent prognostic factor with an adjusted hazard ratio of 1.60 (95% confidence interval 1.07–2.41). The MMP9 Arg279Gln and Arg668Gln SNPs are potential predictors of survival in NSCLC patients. © 2008 Wiley-Liss, Inc.