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Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan

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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.

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Author notes

  1. Mitsushige Sugimoto

    Present address: Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Blvd., (111D) Rm 3A-320, Houston, TX, 77030, USA

Authors and Affiliations

  1. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Mitsushige Sugimoto, Chise Kodaira, Masafumi Nishino, Mihoko Yamade, Mutsuhiro Ikuma & Akira Hishida

  2. Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Takahisa Furuta

  3. First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Haruhiko Sugimura

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  1. Mitsushige Sugimoto
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Sugimoto, M., Furuta, T., Kodaira, C. et al. Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan. J Gastroenterol 43, 751–761 (2008). https://doi.org/10.1007/s00535-008-2221-6

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