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Carcinogenesis Advance Access originally published online on March 26, 2007
Carcinogenesis 2007 28(9):2036-2040; 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*, Takahisa Furuta1, Naohito Shirai2, Chise Kodaira, Masafumi Nishino, Mutsuhiro Ikuma, Haruhiko Sugimura3 and Akira Hishida

First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan
1 Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan
2 Department of Gastroenterology, Enshu General Hospital, 1-1-1 Tyuou, Hamamatsu, Shizuoka 430-0929, Japan
3 First Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan

* To whom correspondence should be addressed. Tel: +81 53 435 2261; Fax: +81 53 434 9447; Email: mitsu{at}hama-med.ac.jp

Backgrounds and aims: The renin–angiotensin (RA) 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 Helicobacter 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% confidence interval (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 RA system plays an important role in the pathogenesis of gastric cancer.

Abbreviations: ACE, angiotensin I-converting enzyme; AGT, angiotensinogen; AT1R, angiotensin II type-1 receptor; CI, confidence interval; OR, odds ratio; PG, pepsinogen; RA, renin–angiotensin

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


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