Statins attenuate helicobacter pylori CagA translocation and reduce incidence of gastric cancer: In Vitro and population-based case-control studies

Chun Jung Lin, Wei Chih Liao, Hwai Jeng Lin, Yuan Man Hsu, Cheng Li Lin, Yu An Chen, Chun Lung Feng, Chih Jung Chen, Min Chuan Kao, Chih Ho Lai, Chia Hung Kao

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25 Citations (Scopus)

Abstract

Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich microdomains (also called lipid rafts), which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA), which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD) was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.70-0.83). In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12-0.50). Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer.

Original languageEnglish
Article numbere0146432
JournalPLoS One
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 5 2016

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Lin, C. J., Liao, W. C., Lin, H. J., Hsu, Y. M., Lin, C. L., Chen, Y. A., Feng, C. L., Chen, C. J., Kao, M. C., Lai, C. H., & Kao, C. H. (2016). Statins attenuate helicobacter pylori CagA translocation and reduce incidence of gastric cancer: In Vitro and population-based case-control studies. PLoS One, 11(1), [e0146432]. https://doi.org/10.1371/journal.pone.0146432