title: Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects.
abstract: OBJECTIVE
  Chronic obstructive pulmonary disease (COPD) is often accompanied by lung cancer. Among the genes that may play a role in the occurrence of COPD and lung cancer are those encoding the proteolytic enzymes, such as matrix metalloproteinases (MMPs) and their tissue inhibitors. The objective of this study was to find MMPs-associated markers useful in the identification of COPD subjects with increased susceptibility to developing lung cancer.
  
  
  METHODS
  We compared the frequency of single nucleotide polymorphisms in genes coding for matrix proteinases (MMP1, MMP2, MMP3, MMP9, MMP12) as well as tissue inhibitor of metalloproteinases (TIMP1) in two groups of subjects: COPD patients (54 subjects) and COPD patients diagnosed for lung cancer occurrence (53 subjects).The levels of the respective proteins in blood serum were also analyzed.
  
  
  RESULTS
  The frequencies of 2 genotypes, MMP3 rs3025058 and MMP3 rs678815, were significantly different between the studied groups. In both cases, more heterozygotes and less homozygotes (both types) were observed in the COPD group than in the COPD + cancer group. A significantly higher TIMP1 level in blood serum was observed in the COPD + cancer group than in the COPD group. There were no statistically significant differences in MMPs blood levels between the studied groups. In addition, no genotype-associated differences in TIMP1 or MMPs blood levels were observed.
  
  
  CONCLUSIONS
  Homozygocity for MMP3 rs3025058 and rs678815 polymorphisms is a potential marker of enhanced susceptibility to lung cancer development among COPD subjects.
authors.affiliation: Institute of Nuclear Chemistry and Technology, Centre for Radiobiology and Biological Dosimetry, Warsaw, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Brzóska
authors.affiliation: Institute of Nuclear Chemistry and Technology, Centre for Radiobiology and Biological Dosimetry, Warsaw, Poland.
authors.forename: Teresa
authors.initials: T
authors.lastname: Bartłomiejczyk
authors.affiliation: Institute of Nuclear Chemistry and Technology, Centre for Radiobiology and Biological Dosimetry, Warsaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sochanowicz
authors.affiliation: Institute of Nuclear Chemistry and Technology, Centre for Radiobiology and Biological Dosimetry, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cymerman
authors.affiliation: Institute of Tuberculosis and Lung Diseases, Third Department of Lung Diseases, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Grudny
authors.affiliation: Institute of Tuberculosis and Lung Diseases, Department of Diagnosis and Treatment of Respiratory Insufficiency, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kołakowski
authors.affiliation: Institute of Rural Health, Department of Molecular Biology and Translational Research, Lublin, Poland; University of Information Technology and Management, Faculty of Medicine, Department of Medical Biology and Translational Research, Rzeszów, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Kapka-Skrzypczak
authors.affiliation: Institute of Rural Health, Department of Molecular Biology and Translational Research, Lublin, Poland; University of Information Technology and Management, Faculty of Medicine, Department of Medical Biology and Translational Research, Rzeszów, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruszewski
authors.affiliation: Institute of Tuberculosis and Lung Diseases, Department of Diagnosis and Treatment of Respiratory Insufficiency, Warsaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Sliwiński
authors.affiliation: Institute of Tuberculosis and Lung Diseases, Third Department of Lung Diseases, Warsaw, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Roszkowski-Śliż
mesh_terms: D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000235:genetics*; D020782:Matrix Metalloproteinases / Q000097:blood / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000235:genetics
chemical_list: D005819:Genetic Markers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3