title: A functional polymorphism (-1607 1G→2G) in the matrix metalloproteinase-1 promoter is associated with development and progression of lung cancer.
abstract: BACKGROUND
  Matrix metalloproteinase-1 (MMP-1), an interstitial collagenase, plays an important role in the breakdown of extracellular matrix and mediates pathways of apoptosis, angiogenesis, and immunity. It has been demonstrated that the overexpression of this enzyme is associated with tumor initiation, invasion, and metastasis. The -1607 single guanine (1G)-to-2G polymorphism (reference single nucleotide polymorphism 1799750) in the MMP-1 promoter region creates an E26 (Ets) binding site and results in transcriptional up-regulation. The authors hypothesized that this MMP-1 polymorphism may affect susceptibility to the development and progression of cancer.
  
  
  METHODS
  The authors investigated their hypothesis in a lung cancer case-control study. Genotypes were analyzed in 825 patients with lung cancer and in 825 controls. Odds ratios were estimated by multivariate logistic regression, and a meta-analysis also was conducted to verify the findings.
  
  
  RESULTS
  Patients who had the MMP-1 2G/2G genotype had a 1.71-fold increased risk of lung cancer (95% confidence interval, 1.22-fold to 2.41-fold increased risk) compared with patients who had the 1G/1G genotype. Moreover, when patients with stage I disease were considered as a reference group, patients who carried the 2G/2G genotype had a significantly increased risk of invasive disease (stage III-IV: odds ratio, 2.02; 95% confidence interval, 1.09-3.74) compared with patients who had the 1G/1G genotype. Pooled results from the meta-analysis confirmed that those who had the 2G/2G genotype had a significantly increased risk of lung cancer compared with those who had the 1G/1G genotype, consistent with the case-control findings.
  
  
  CONCLUSIONS
  The current study demonstrated that the MMP-1 -1607 1G-to-2G polymorphism is associated with susceptibility to both development and progression of lung cancer.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Shaofa
authors.initials: S
authors.lastname: Nie
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk
chemical_list: D020781:Matrix Metalloproteinase 1