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.
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-infectedpatients. 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-infectedpatients. 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: Christoph Röcken; Uwe Lendeckel; Jutta Dierkes; Sabine Westphal; Stacy Carl-McGrath; Brigitte Peters; Sabine Krüger; Peter Malfertheiner; Albert Roessner; Matthias P A Ebert Journal: Clin Cancer Res Date: 2005-04-01 Impact factor: 12.531
Authors: S Ye; S Dhillon; S J Turner; A C Bateman; J M Theaker; R M Pickering; I Day; W M Howell Journal: Cancer Res Date: 2001-02-15 Impact factor: 12.701
Authors: V Noë; B Fingleton; K Jacobs; H C Crawford; S Vermeulen; W Steelant; E Bruyneel; L M Matrisian; M Mareel Journal: J Cell Sci Date: 2001-01 Impact factor: 5.285