Document Detail


Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan.
MedLine Citation:
PMID:  18958543     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Mitsushige Sugimoto; Takahisa Furuta; Chise Kodaira; Masafumi Nishino; Mihoko Yamade; Mutsuhiro Ikuma; Haruhiko Sugimura; Akira Hishida
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-29
Journal Detail:
Title:  Journal of gastroenterology     Volume:  43     ISSN:  0944-1174     ISO Abbreviation:  J. Gastroenterol.     Publication Date:  2008  
Date Detail:
Created Date:  2008-10-29     Completed Date:  2009-02-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9430794     Medline TA:  J Gastroenterol     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  751-61     Citation Subset:  IM    
Affiliation:
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
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MeSH Terms
Descriptor/Qualifier:
Aged
Asian Continental Ancestry Group / genetics
Case-Control Studies
Chymases / genetics*
Cohort Studies
Duodenal Ulcer / genetics,  microbiology,  pathology
Female
Gastritis / genetics,  microbiology,  pathology
Genetic Predisposition to Disease
Helicobacter Infections / ethnology,  genetics*,  pathology
Helicobacter pylori*
Humans
Japan
Male
Matrix Metalloproteinase 7 / genetics*
Middle Aged
Polymorphism, Genetic / genetics*
Stomach Neoplasms / genetics*,  microbiology,  pathology
Stomach Ulcer / genetics,  microbiology,  pathology
Chemical
Reg. No./Substance:
EC 3.4.21.39/Chymases; EC 3.4.24.23/Matrix Metalloproteinase 7

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