title: Genetic polymorphisms in MMP 2, 9 and 3 genes modify lung cancer risk and survival.
abstract: BACKGROUND
  Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of tumour progression, including the later stages of invasion and metastasis. Genetic variants in the MMP genes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. We have investigated the association between the -735 C/T, the -1171 5A/6A, and the -1562 C/T polymorphisms in the MMP2, MMP3 and MMP9 genes, respectively, and the risk and survival of lung cancer.
  
  
  METHODS
  The case-control study includes 879 lung cancer patients and 803 controls from a Caucasian population in Spain (CAPUA study). Genotypes were determined by PCR-RFLP. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. The Kaplan-Meier method, long-rank test and Cox's were used for the survival analysis.
  
  
  RESULTS
  The MMP9 -1562 T/T genotype was associated with a statistically significant decreased risk of developing lung cancer (OR = 0.23; 95% CI: 0.06-0.85), whereas no association was found for the MMP2 -735 C/T and MMP3 -1171 5A/6A polymorphisms. The MMP2 -735 T/T genotype was statistically significantly associated with a decreased survival in non-small cell lung cancer (NSCLC) patients, identified as an independent prognosis factor of survival (hazard ratio (HR) = 1.79; 95% CI: 1.00-3.20). In contrast, no association was found between the MMP3 -1171 5A/6A and the MMP9 -1562 C/T polymorphisms and survival.
  
  
  CONCLUSIONS
  These findings support the hypothesis that the MMP9 -1562 C/T polymorphism is associated with a protective effect against the development of lung cancer and suggest that the MMP2 -735 C/T polymorphism modify the length of survival in NSCLC patients.
authors.affiliation: Departamento de Medicina, Unidad de Epidemiología Molecular del Cáncer del Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Spain. atardon@uniovi.es
authors.forename: Patricia
authors.initials: P
authors.lastname: González-Arriaga
authors.forename: Teresa
authors.initials: T
authors.lastname: Pascual
authors.forename: Arturo
authors.initials: A
authors.lastname: García-Alvarez
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Somoano
authors.forename: M Felicitas
authors.initials: MF
authors.lastname: López-Cima
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013030:Spain; D016019:Survival Analysis
chemical_list: D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9