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

• Published in: Alimentary pharmacology & therapeutics Vol. 22; no. 10; pp. 1033 - 1040
• Main Authors: SUGIMOTO, M., FURUTA, T., SHIRAI, N., NAKAMURA, A., KAJIMURA, M., SUGIMURA, H., HISHIDA, A., ISHIZAKI, T.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.2005; Blackwell
• Subjects: Aged; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Cytochrome P-450 CYP2C19; Digestive system; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Predisposition to Disease; Helicobacter Infections - epidemiology; Helicobacter Infections - genetics; Helicobacter pylori; Humans; Japan - epidemiology; Male; Medical sciences; Middle Aged; Mixed Function Oxygenases - genetics; Pharmacology. Drug treatments; Polymorphism, Genetic - genetics; Polymorphism, Restriction Fragment Length; Risk Factors; Stomach Neoplasms - epidemiology; Stomach Neoplasms - genetics; Stomach Neoplasms - microbiology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Asia; Japan; Human; Spirillales; Enzyme; Isozyme; Cytochrome P450; Spirillaceae; Genotype; Malignant tumor; Stomach cancer; Epidemiology; Infection; Helicobacter pylori; Risk factor; Bacteriosis; Development; Digestive diseases; Bacteria; Gastric disease
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2005.02678.x

Summary 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.