title: Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) are a family of enzymes that degrade most macromolecules making up the extracellular matrix. MMPs are involved in not only the gastric mucosal inflammatory response but also the pathogenesis of Helicobacter pylori-associated diseases. In the renin-angiotensin system, chymase (CMA) is related to gastric carcinogenesis and angiogenesis in H. pylori-infected patients. We aimed to clarify the association of MMP-7-181 and CMA/B polymorphisms with susceptibility to gastric cancer and cancer progression in H. pylori-infected patients.
  
  
  METHODS
  We assessed the MMP-7-181 and CMA/B polymorphisms in H. pylori-positive patients with gastric cancer (n = 160), gastric ulcer (n = 157), duodenal ulcer (n = 121), and H. pylori-positive gastritis alone as controls (n = 156).
  
  
  RESULTS
  For gastric cancer risk, the age-and sex-adjusted odds ratio (OR) of the MMP-7-181 G allele carrier relative to the A/A genotype was significantly increased [OR, 2.32; 95% confidence interval (CI), 1.24-4.35], especially in patients with noncardia cancer (OR, 2.31; 95% CI, 1.22-4.36) and those with clinical stage III or IV cancer (OR, 3.66; 95% CI, 1.54-8.73). Carriage of the CMA/B A allele was significantly associated with gastric cancer development (OR, 1.73; 95% CI, 1.10-2.71). Simultaneous carriage of both the MMP-7-181 G allele and the CMA/B A allele dramatically increased the gastric cancer risk (OR, 8.18; 95% CI, 2.79-23.93).
  
  
  CONCLUSIONS
  In Japan, carriage of the MMP-7-181 G allele and of the CMA/B A allele were each associated with an increased risk for H. pylori-related noncardia gastric cancer development. MMP-7-181 and CMA/B genotyping tests might be useful tools for screening for individuals with higher gastric cancer risk.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.forename: Chise
authors.initials: C
authors.lastname: Kodaira
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nishino
authors.forename: Mihoko
authors.initials: M
authors.lastname: Yamade
authors.forename: Mutsuhiro
authors.initials: M
authors.lastname: Ikuma
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D053818:Chymases / Q000235:genetics*; D015331:Cohort Studies; D004381:Duodenal Ulcer / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D005260:Female; D005756:Gastritis / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D007564:Japan; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D013276:Stomach Ulcer / Q000235:genetics / Q000382:microbiology / Q000473:pathology
chemical_list: D053818:Chymases; D020783:Matrix Metalloproteinase 7