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



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  • Personal Author:
  • Description:
    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. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    1078-0432
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Volume:
    12
  • Issue:
    18
  • NIOSHTIC Number:
    nn:20056727
  • Citation:
    Clin Cancer Res 2006 Sep; 12(18):5448-5453
  • Contact Point Address:
    David C. Christiani, Harvard School of Public Health Building I, Room 1407, 665 Huntington Avenue, Boston, MA 02115
  • Email:
    dchris@hohp.harvard.edu
  • Federal Fiscal Year:
    2006
  • Performing Organization:
    Harvard School of Public Health
  • Peer Reviewed:
    True
  • Start Date:
    20050701
  • Source Full Name:
    Clinical Cancer Research
  • End Date:
    20280630
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:bd0149fb3228195cf5304ad263a1a323b3ce2ae873fb169b6a81ae43d406a38162fd0055b41f2bbca97ec9ce5dee06ee59a36330a064e7a7e139cc50e0f39824
  • Download URL:
  • File Type:
    Filetype[PDF - 231.47 KB ]
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