Table 1.
Summary of clinical studies associating gastric cancer with long-term use of proton pump inhibitors
| Author, year | Study design, country | Study period | Source of database | No. of case and control | Information of PPI | Adjustment | Main outcomes |
| Garcia-Rodriguez et al[24], 2006 | Nested case-control, retrospective, United Kingdom | 1994-2001 | The general practitioners research database in the United Kingdom | 522/10000 | Duration, indication | Age, sex, calendar year, smoking, alcohol consumption, body mass index, gastro-esophageal reflux, hiatal hernia, peptic ulcer, and dyspepsia | OR for gastric cardia adenocarcinoma: 1.06 (0.57-2.00); gastric non-cardia adenocarcinoma: 1.75 (1.10-2.79) |
| Tamim et al[25], 2008 | Case control, retrospective, Canada | 1995-2003 | Quebec health insurance plan | 1598/12991 | Type, dose, exposure time | Number of drug prescriptions, total length of hospitalizations, number of visits to GPs, specialists, and emergency rooms during the year before the diagnosis | Adjusted OR: 1.40 (1.08-1.51); 1st quartile: 1.66 (1.24-2.23); 2nd quartile: 1.37 (1.00-1.88); 3rd quartile: 1.57 (1.17-2.10); 4th quartile: 1.20 (0.85-1.70) |
| Poulsen et al[26], 2009 | Population-based cohort, retrospective, Denmark | 1990-2003 | Danish National Health-care System | 109/not reported | Type, year of follow-up, no. of prescription | Age, gender, calendar period, gastroscopy (≥ 1 yr before censoring events), use of NSAIDs and H. pylori eradication | IRR for gastric cancer: 1.2 (0.8-2.0) among PPI users with the largest number of prescriptions (15+) or the longest follow-up (5+) |
| Cheung et al[29], 2018 | Population-based cohort study, retrospective, Hong Kong | 2003-2012 | Clinical Data Analysis and Reporting System of the Hong Kong Hospital Authority | 153/63397 | Frequency, duration | Age of receiving H. pylori eradication therapy, sex, smoking, alcohol use, comorbidities, concomitant medications | HR for gastric cancer: 2.44 (1.42-4.20); ≥ 1 yr: 5.04 (1.23-20.61); ≥ 2 yr: 6.65 (1.62-27.26); ≥ 3 yr: 8.34 (2.02-34.41). The adjusted absolute risk difference for PPIs vs nonPPIs use: 4.29 (1.25-9.54) per 10000 person-yr. |
| Brusselaers et al[33], 2017 | Population-based cohort study, retrospective, Sweden | 2005-2012 | The Swedish Prescribed Drug Registry | 2219/794848 | Indication, cumulative defined daily dosages, estimated number of days | Age, sex, calendar period, indication of PPI, maintenance use (≥ 180 d) of aspirin or other NSAIDs | SIR: 3.38 (3.23-3.53) in both sexes, all age groups and all indication groups; < 1 yr: 12.82 (12.19-13.47); 1.0-2.9 yr: 2.19 (1.98 to 2.42); 3.0-4.9 yr: 1.10 (0.91-1.31); ≥ 2 yr: 0.61 (0.52-0.72) |
PPI: Proton pump inhibitor; OR: Odds ratio; GP: General physician; NSAID: Nonsteroidal anti-inflammatory drug; H. pylori: Helicobacter pylori; IRR: Incidence rate ratio; HR: Hazard ratio; SIR: Standardized incidence ratio.