Influences of chymase and angiotensin I-converting enzyme gene polymorphisms on gastric cancer risks in Japan

Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1929-34. doi: 10.1158/1055-9965.EPI-06-0339.

Abstract

Backgrounds and aims: The renin-angiotensin system plays an important role in homeostasis. Angiotensin II, which is generated by chymase and angiotensin I-converting enzyme (ACE), controls blood pressure as well as angiogenesis and cell proliferation. The aim of this study was to clarify the association of the chymase gene (CMA/B) and ACE polymorphisms with susceptibility to gastric cancer and peptic ulcer.

Methods: We assessed CMA/B A/G and ACE insertion/deletion (I/D) polymorphisms in H. pylori-positive gastric cancers (n = 119), gastric ulcers (n = 127), and duodenal ulcers (n = 105), and controls (n = 294) consisting of H. pylori-positive gastritis alone (n = 162) and H. pylori-negative subjects (n = 132) by PCR methods.

Results: In CMA/B polymorphism, the age- and sex-adjusted odds ratios (OR) of A/A and A/G genotypes relative to the G/G genotype for gastric cancer risk were 7.115 (95% confidence interval, 1.818-27.845) and 1.956 (95% confidence interval, 1.137-3.366), respectively. There was an increased risk for gastric ulcer in the A/A genotype (OR, 3.450; 1.086-10.960). However, there was no association between ACE polymorphism and susceptibility to gastric cancer and peptic ulcer. In allele combination analysis of CMA/B and ACE polymorphisms, the A/I allele combinations (CMA/B G/A or A/A and ACE I/I genotype) significantly increased the risk of gastric cancer development (OR, 4.749, 2.050-11.001) compared with the G/I allele combinations (CMA/B G/G and ACE I/I genotype).

Conclusions: The CMA/B polymorphism was associated with an increased risk for gastric cancer and gastric ulcer development. The genotyping test of the renin-angiotensin system could be useful for the screening of individuals with higher risks of gastric cancer and gastric ulcer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chymases / genetics*
  • Duodenal Ulcer / enzymology
  • Duodenal Ulcer / genetics
  • Female
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastritis, Atrophic / enzymology
  • Gastritis, Atrophic / genetics
  • Gene Deletion
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Helicobacter Infections / complications
  • Helicobacter pylori
  • Homeostasis / genetics
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pepsinogen A / blood
  • Peptidyl-Dipeptidase A / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Renin-Angiotensin System / genetics
  • Risk Factors
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / epidemiology*
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Stomach Ulcer / enzymology
  • Stomach Ulcer / genetics

Substances

  • Pepsinogen A
  • Peptidyl-Dipeptidase A
  • Chymases