title: Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma.
abstract: BACKGROUND
  Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls.
  
  
  METHODS
  Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression.
  
  
  RESULTS
  No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95% CI: 1.20-2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95% CI: 1.08-3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression.
  
  
  CONCLUSIONS
  These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis.
authors.affiliation: INSERM U775 et Université René Descartes, Paris, France. astrid-lievre@orange.fr <astrid-lievre@orange.fr>
authors.forename: Astrid
authors.initials: A
authors.lastname: Lièvre
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Milet
authors.forename: Jérôme
authors.initials: J
authors.lastname: Carayol
authors.forename: Delphine
authors.initials: D
authors.lastname: Le Corre
authors.forename: Chantal
authors.initials: C
authors.lastname: Milan
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pariente
authors.forename: Bernard
authors.initials: B
authors.lastname: Nalet
authors.forename: Jacques
authors.initials: J
authors.lastname: Lafon
authors.forename: Jean
authors.initials: J
authors.lastname: Faivre
authors.forename: Claire
authors.initials: C
authors.lastname: Bonithon-Kopp
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.forename: Catherine
authors.initials: C
authors.lastname: Bonaiti-Pellié
authors.forename: Pierre
authors.initials: P
authors.lastname: Laurent-Puig
mesh_terms: D018256:Adenomatous Polyps / Q000201:enzymology / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020781:Matrix Metalloproteinase 1