Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan.
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.
Sugimoto
Mitsushige
M
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Furuta
Takahisa
T
Kodaira
Chise
C
Nishino
Masafumi
M
Yamade
Mihoko
M
Ikuma
Mutsuhiro
M
Sugimura
Haruhiko
H
Hishida
Akira
A
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
D053818:Chymases; D020783:Matrix Metalloproteinase 7