Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection

Aliment Pharmacol Ther. 2005 Nov 15;22(10):1033-40. doi: 10.1111/j.1365-2036.2005.02678.x.


Background: Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s).

Aim: To clarify the association between CYP2C19 polymorphisms and gastric cancer development in Japanese. Methods : We determined CYP2C19 genotypes (CYP2C19*1, *2 and *3) in 111 Helicobacter pylori-positive patients with gastric cancer and 315 H. pylori-positive controls without gastric cancer consisting of patients with gastritis only or peptic ulcer. Frequencies of CYP2C19 genotypes and serum pepsinogen I and II levels, a biomarker of gastric atrophy, in the gastric cancers and controls were compared.

Results: Frequencies of homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers were 31.5%, 42.3% and 26.2% in the gastric cancers and 38.1%, 47.0% and 14.9% in the controls, respectively (P = 0.046). Poor metabolizers were associated with an increased risk for developing gastric cancer with the age- and sex-adjusted odds ratio (OR) of 1.975 [95% confidence interval (CI): 1.068-3.649], especially for diffuse type (OR: 3.385, CI: 1.187-9.648). There is no significant association between CYP2C19 genotypes and serum pepsinogen I level or pepsinogen I/II ratios, although serum pepsinogen I level in gastric cancers were significantly decreased.

Conclusions: In H. pylori-positive Japanese, poor metabolizers of CYP2C19 appear to be at an increased risk for developing gastric cancer, especially diffuse type, and may require an intensive follow-up for scrutinizing possible gastric cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Cytochrome P-450 CYP2C19
  • Female
  • Genetic Predisposition to Disease
  • Helicobacter Infections / epidemiology*
  • Helicobacter Infections / genetics
  • Helicobacter pylori*
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / genetics*
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Restriction Fragment Length
  • Risk Factors
  • Stomach Neoplasms / epidemiology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / microbiology


  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19