This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heist, R. S. Articles by Christiani, D. C. Search for Related Content PubMed PubMed Citation Articles by Heist, R. S. Articles by Christiani, D. C.

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

Authors' Affiliations: ¹ Massachusetts General Hospital and ² Harvard School of Public Health, Boston, Massachusetts

Requests for reprints: David C. Christiani, Harvard School of Public Health Building I, Room 1407, 665 Huntington Avenue, Boston, MA 02115. E-mail: dchris{at}hohp.harvard.edu.

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.

This article has been cited by other articles:

				S. Hughes, O. Agbaje, R. L. Bowen, D. L. Holliday, J. A. Shaw, S. Duffy, and J. L. Jones Matrix Metalloproteinase Single-Nucleotide Polymorphisms and Haplotypes Predict Breast Cancer Progression Clin. Cancer Res., November 15, 2007; 13(22): 6673 - 6680. [Abstract] [Full Text] [PDF]

				S. Wilkening, J. L. Bermejo, and K. Hemminki MDM2 SNP309 and cancer risk: a combined analysis Carcinogenesis, November 1, 2007; 28(11): 2262 - 2267. [Abstract] [Full Text] [PDF]

				A. G. Schwartz, G. M. Prysak, C. H. Bock, and M. L. Cote The molecular epidemiology of lung cancer Carcinogenesis, March 1, 2007; 28(3): 507 - 518. [Abstract] [Full Text] [PDF]