Matrix Metalloproteinase Polymorphisms and Survival in Stage I Non-Small Cell Lung Cancer

Heist, Rebecca Suk, Marshall, Ariela L., Liu, Geoffrey, Zhou, Wei, Su, Li, Neuberg, Donna, Lynch, Thomas J., Wain, John and Christiani, David C. (2006) Matrix Metalloproteinase Polymorphisms and Survival in Stage I Non-Small Cell Lung Cancer. Clinical Cancer Research, 12 (18). pp. 5448-5453. ISSN 1078-0432

Full text not available from this repository. (Request a copy)

Abstract

Purpose: The matrix metalloproteinases (MMP) are a family of enzymes that can degrade extracellular matrix and facilitate invasion through the basement membrane. Several polymorphisms in MMP-1, MMP-2, MMP-3, and MMP-12 have been described, some of which lead to differential transcription. We hypothesized that polymorphisms in these MMP genes may be associated with survival outcomes in early-stage non–small cell lung cancer (NSCLC). Experimental Design: We evaluated the relationship between MMP-1, MMP-2, MMP-3, and MMP-12 polymorphisms and both recurrence-free survival (RFS) and overall survival (OS) among 382 patients with stage I NSCLC. Analyses of genotype associations with survival outcomes were done using Cox proportional hazards models and Kaplan-Meier methods and the log-rank test. Results: Patients carrying the variant G allele of the MMP-12 1082A/G polymorphism had significantly worse outcomes [crude hazard ratio (HR) for OS 1.74; 95% confidence interval (95% CI), 1.18-2.58, P = 0.006; crude HR for RFS, 1.53; 95% CI, 1.05-2.23, P = 0.03]. After adjusting for age, sex, stage, pack-years of smoking, and histologic subtype, the MMP-12 1082A/G polymorphism remained significantly associated with survival outcomes [adjusted HR (AHR) for OS, 1.94; 95% CI, 1.28-2.97, P = 0.002; AHR for RFS, 1.61; 95% CI, 1.07-2.41, P = 0.02]. None of the other MMP polymorphisms was significantly associated with survival. Conclusions: Our results show that patients with stage I NSCLC carrying the variant G allele of the MMP-12 1082A/G polymorphism have worse survival.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Rhiannon Harvey
Date Deposited: 12 Jul 2011 11:13
Last Modified: 21 Apr 2020 19:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/33543
DOI: 10.1158/1078-0432.CCR-06-0262

Actions (login required)

View Item View Item