title: Statins Attenuate Helicobacter pylori CagA Translocation and Reduce Incidence of Gastric Cancer: In Vitro and Population-Based Case-Control Studies.
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.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.|Department of Pulmonary and Critical Care Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Liao
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University, Shuang-Ho Hospital, New Taipei, Taiwan.
authors.forename: Hwai-Jeng
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Yuan-Man
authors.initials: YM
authors.lastname: Hsu
authors.affiliation: Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Cheng-Li
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Lung
authors.initials: CL
authors.lastname: Feng
authors.affiliation: Division of Paediatric Infectious Diseases, Department of Paediatrics, Chang Gung Children's Hospital and Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Min-Chuan
authors.initials: MC
authors.lastname: Kao
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung, Taiwan.|Department of Nursing, Asia University, Taichung, Taiwan.|Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.|Department of Nuclear Medicine, PET Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015151:Immunoblotting; D015994:Incidence; D008148:Lovastatin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D011159:Population Surveillance / Q000379:methods; D021381:Protein Transport / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C080866:cagA protein, Helicobacter pylori; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin