Matrix metalloproteinase polymorphisms and survival in stage I non-small cell lung cancer

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% Cl, 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% Cl, 1.28-2.97, P = 0.002; AHR for RFS, 1.61; 95% Cl, 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.