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


METHODS
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.
Heist
Rebecca Suk
RS
Massachusetts General Hospital and Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Marshall
Ariela L
AL
Liu
Geoffrey
G
Zhou
Wei
W
Su
Li
L
Neuberg
Donna
D
Lynch
Thomas J
TJ
Wain
John
J
Christiani
David C
DC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis
D020782:Matrix Metalloproteinases