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The Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism Is Linked to Early Gastric Cancer

¹ Fred Hutchinson Cancer Center, Public Health Sciences, Seattle, Washington; ² Department of Gastroenterology, Hepatology and Infectious Diseases; Institutes of ³ Experimental Internal Medicine, ⁴ Clinical Chemistry, and ⁵ Pathology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany; ⁶ Medizinische Poliklinik der Ludwig-Maximilians Universität, Munich, Germany; and ⁷ Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany

Requests for reprints: Matthias Ebert, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Phone: 49-391-672-1520; Fax: 49-391-672-90054; E-mail: matthias.ebert{at}medizin.uni-magdeburg.de.

The insertion/deletion polymorphism of the angiotensin I–converting enzyme (ACE) gene has recently been linked to the pathogenesis and progression of human cancers. Using genomic DNA from 88 patients with early gastric cancer confined either to mucosa (pT_1a) or submucosa (pT_1b), we assessed the insertion (I) and deletion (D) polymorphism by PCR analysis and compared it with a large noncancer control population (n = 145). In the noncancer control group, the II genotype was observed in 33 (23%) individuals, whereas the ID and DD genotypes were found in 72 (50%) and 40 (27%) individuals, respectively. Interestingly, in the cancer group, we found the II genotype in six (7%) patients and the ID genotype in 46 (52%) individuals, whereas the DD genotype was observed in 36 (41%) individuals (P = 0.0034). Accordingly, the odds ratio for the II genotype was 0.20 [95% confidence interval (95% CI), 0.08-0.54; P = 0.009] and 0.55 for the ID/II genotype (95% CI, 0.31-0.96; P = 0.044) using the high-activity genotype DD as the reference category. No correlation was found among tumor type, tumor stage, the presence of Helicobacter pylori, and the ACE genotype. Our study provides further evidence that the ACE insertion/deletion gene polymorphism may be linked to the development of early gastric cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2987–9)

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