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Carcinogenesis Advance Access published online on March 26, 2007
Carcinogenesis, doi:10.1093/carcin/bgm074
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Role of angiotensinogen gene polymorphism on Helicobacter pylori infection-related gastric cancer risk in Japanese

Mitsushige Sugimoto, MD, PhD1, Takahisa Furuta, MD, PhD2, Naohito Shirai, MD, PhD3, Chise Kodaira, MD1, Masafumi Nishino, MD1, Mutsuhiro Ikuma, MD, PhD1, Haruhiko Sugimura, MD, PhD4 and Akira Hishida, MD, PhD1

1 First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, JAPAN
2 Center for Clinical Research, Hamamatsu University School of Medicine, Shizuoka, JAPAN
4 First Department of Pathology, Hamamatsu University School of Medicine, Shizuoka, JAPAN
3 Department of Gastroenterology, Enshu General Hospital, Shizuoka, JAPAN

Corresponding author: Mitsushige Sugimoto, MD, PhD, First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan, Tel: +81-53-435-2261, Fax: +81-53-434-9447, E-mail: mitsu{at}hama-med.ac.jp

Backgrounds and aims: The renin-angiotensin system including angiotensinogen (AGT), angiotensin I and angiotensin II influences the regulation of cell proliferation, angiogenesis and inflammation. AGT-20 A/C polymorphism is associated with the plasma AGT and angiotensin II levels. The aim of this study was to clarify the association of AGT-20 A/C polymorphism with susceptibility to gastric cancer and peptic ulcer in Japanese.

Methods: We assessed the AGT-20 A/C polymorphism in H. pylori-positive patients with gastric cancer (n = 135), gastric ulcer (n = 148), and duodenal ulcer (n = 113) and controls (n = 292) consisting of H. pylori-positive gastritis alone (n = 160) and H. pylori-negative subjects (n = 132).

Results: The age- and sex-adjusted odds ratios (ORs) of AGT-20 A/C and C/C genotypes relative to A/A genotype for gastric cancer risk were 1.695 (95%CI: 1.035 – 2.777) and 2.259 (95%CI: 0.351 – 14.533), respectively. The AGT-20 C allele increased the gastric cancer risk (OR: 1.685, 95%CI: 1.037 – 2.736), especially the intestinal type of gastric cancer (OR: 1.792, 95%CI: 1.040 – 3.089). However, there was no association between the AGT-20 polymorphism and susceptibility to peptic ulcer.

Conclusions: The carriage of AGT-20 C allele was associated with an increased risk for H. pylori-related gastric cancer development in Japanese, indicating that the renin-angiotensin system plays an important role in the pathogenesis of gastric cancer.

This work was supported in part by a Grant-in-Aid from YOKOYAMA Foundation for Clinical Pharmacology, and from the 21st century COE program Medical Photonics (Hamamatsu University School of Medicine).

Received January 10, 2007; revised February 26, 2007; accepted March 15, 2007.


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