Influences of chymase and angiotensin I-converting enzyme gene polymorphisms on gastric cancer risks in Japan.
OBJECTIVE
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.
Sugimoto
Mitsushige
M
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan. mitsu@hama-med.ac.jp
Furuta
Takahisa
T
Shirai
Naohito
N
Ikuma
Mutsuhiro
M
Sugimura
Haruhiko
H
Hishida
Akira
A
D000368:Aged; D053818:Chymases / Q000235:genetics*; D004381:Duodenal Ulcer / Q000201:enzymology / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005757:Gastritis, Atrophic / Q000201:enzymology / Q000235:genetics; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020116:Pepsinogen A / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D013276:Stomach Ulcer / Q000201:enzymology / Q000235:genetics
D020116:Pepsinogen A; D007703:Peptidyl-Dipeptidase A; D053818:Chymases