E0687 - The Risk of Gastric Cancer (Overall and Cardia Only) With the Use of Proton Pump Inhibitors in Observational Studies: A Systematic Review and Meta-Analysis

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

SP

Sharon Pan, MS

Texas A&M Health Science Center College of Medicine
Bryan, TX

Sharon Pan, MS¹, Ghida Akhdar, MD², Aaron Thrift, PhD², Hashem El-Serag, MD, MPH²
¹Texas A&M Health Science Center College of Medicine, Bryan, TX; ²Baylor College of Medicine, Houston, TX

Introduction: There are a number of reports that raise safety concerns on the association between proton pump inhibitors (PPIs) and the risk of gastric cancer both overall as well as isolated gastric cardia.

Methods: We performed an updated systematic review and meta-analysis of observational studies published through January 2022 that examined the association between > 6 months PPI use and the risk of gastric cancer overall and gastric cardia cancer specifically. The inclusion criteria were classification as either a case-control or cohort study, participants 18 years or older, long-term ( > 6 months) PPI use, and gastric cancer as a specified outcome. Excluded studies were case reports, interventional studies, conducted in the pediatric population and used animal models. Study quality was evaluated using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Pooled adjusted risk estimates were calculated using random effects model, and heterogeneity among studies was examined as I²statistic.

Results: We identified 15 publications with 16 studies fulfilling inclusion and exclusion criteria: 6 reported nested case-control studies, 1 case-control, 1 prospective cohort, 6 retrospective cohort, and 1 paper with both case-control and prospective cohort studies. Only 8 studies accounted for H. pylori. Most studies (5 of 8) that examined gastric cardia risks reported no significant association. Pooled unadjusted odds ratios from case control studies were 1.73 (95% CI: 1.43, 1.85) from the 5 overall gastric studies, and 1.26 (95% CI: 0.58, 2.72) from the 6 gastric cardia studies. Most (12 of 15) reported a statistically significant adjusted risk estimate of the association of PPI usage and overall gastric cancer risk, and 3 studies reported no association. Pooled unadjusted risk ratios from cohort studies were 2.57 (95% CI: 2.01, 3.28) from the 8 overall gastric cancer studies, and 1.61 (95% CI: 0.93-2.78) from the 3 gastric cardia studies. The I²ranged between 23 and 88%. Most (15 of 16) had at least moderate risk of bias on the ROBINS-I tool with 1 study with a serious risk of bias.

Discussion: Observational studies show inconsistent and mostly non-significant (individual or pooled) association between PPI and gastric cardia. For overall gastric, pooled results show a modest statistical association, but considerable heterogeneity among studies, study design limitations and at least moderate risk of bias do not support an etiological relationship between PPI and gastric cancer.

Paper (Year of Publication)	Area	Study design	Gastric cancer (GC) site	Patient source	Adjusted risk estimate (95% CI)	ROBINS-I Score
Garcia Rodriguez et. al (2006)	United Kingdom	Nested case-control	Overall (any gastric site) Gastric cardia	General Practitioners Research Database	Adjusted OR for Cardia: 1.06 (CI 0.57-2.00)	Moderate risk
Duan et. al (2008)	United States	Case-control	Overall (any gastric site) Gastric cardia	University of Southern California Cancer Surveillance Program	Adjusted OR for Cardia with PPI use for < 1year: 0.65 (0.31-1.37) 1-3 years: 0.70 (CI 0.32-1.49) > 3 years: 1.29 (CI 0.70-2.36)	Moderate risk
Tamim et. al (2008)	Canada	Nested case-control	Overall (any gastric site) Gastric cardia	Quebec health insurance plan databases	Adjusted OR for overall GC: 1.46 (CI 1.22-1.74) Cardia: 0.58 (CI 0.26-1.32)	Moderate risk
Poulsen et. al (2009)	Denmark	Prospective cohort	Overall (any gastric site)	Danish Civil Registration System	Adjusted IRR for overall GC: 1.2 (CI 0.8-2.0)	Moderate risk
Wennerstrom et. al (2017)	Netherlands	Nested case-control	Overall (any gastric site) Gastric cardia	Danish Civil Registration System	Adjusted HR for Cardia: 2.51 (CI 2.26-2.79)	Moderate risk
Brusselaers et. al (2017)	Sweden	Retrospective cohort	Overall (any gastric site) Gastric cardia	The Swedish Cancer Registry	Adjusted SIR for overall GC: 3.38 (CI 3.25-3.53) Cardia: 3.55 (CI 3.27-3.86)	Moderate risk
Lai et. al (2018)	Taiwan	Case-control	Overall (any gastric site)	Taiwan National Health Insurance Program	Adjusted OR for overall GC: 2.00 (CI 1.36-2.95)	Moderate risk
Peng et. al (2018)	Taiwan	Nested case-control	Overall (any gastric site) Gastric cardia	National Health Insurance Research Database; Registry of Catastrophic Illness	Adjusted OR for overall GC: 2.48 (CI 1.38-4.38) Cardia: 2.58 (CI 1.38-4.83)	Moderate risk
Cheung et. al (2018)	Hong Kong	Retrospective cohort	Overall (any gastric site) Gastric cardia	Clinical Data Analysis and Reporting System of Hong Kong Hospital Authority	Adjusted HR for overall GC: 2.19 (CI 1.31-3.66) Cardia: 1.24 (CI 0.35-4.34)	Moderate risk
Niikura et. al (2018)	Japan	Retrospective cohort	Overall (any gastric site)	University Tokyo Hospital database	Adjusted HR for overall GC: 3.61 (CI 1.49-8.77)	Serious risk
Brusselaers et. al (2019)	Sweden	Retrospective cohort	Overall (any gastric site)	The Swedish Cancer Registry	Adjusted SIR for overall GC: 2.97 (CI 2.83-3.10)	Moderate risk
Lee et. al (2020)	United States	Nested case-control	Overall (any gastric site) Gastric cardia	Kaiser Permanente Northern California	Adjusted OR for overall GC: 1.07 (CI 0.81-1.42) Cardia: 0.98 (CI 0.68-1.40)	Moderate risk
Liu et. al (2020)	United Kingdom	Nested case-control	Overall (any gastric site)	Primary Care Clinical Information Unit	Adjusted OR for overall 1.49 (CI 1.24-1.80)	Moderate risk
Liu et. al (2020)	United Kingdom	Prospective cohort	Overall (any gastric site)	UK BioBank	Adjusted HR for overall GC: 1.28 (CI 0.86-1.90) Cardia: 0.81 (CI 0.40-1.64)	Moderate risk
Ng et. al (2021)	Hong Kong	Retrospective cohort	Overall (any gastric site)	PCI Registry and Clinical Data and Analysis Reporting System	Adjusted HR for overall GC: 2.06 (CI 1.01-4.18)	Low risk
Seo et. al (2021)	South Korea	Retrospective cohort	Overall (any gastric site)	National Health Insurance Service-National Sample Cohort (old version); Observational Medical Outcomes Partnership-Common Data Model	Adjusted HR for overall GC: 2.37 (CI 1.56-3.68)	Moderate risk

Table: Fifteen observational studies that examined the association between PPIs and risk of gastric cancer (GC).

Disclosures:

Sharon Pan indicated no relevant financial relationships.

Ghida Akhdar indicated no relevant financial relationships.

Aaron Thrift indicated no relevant financial relationships.

Hashem El-Serag indicated no relevant financial relationships.

Sharon Pan, MS¹, Ghida Akhdar, MD², Aaron Thrift, PhD², Hashem El-Serag, MD, MPH². E0687 - The Risk of Gastric Cancer (Overall and Cardia Only) With the Use of Proton Pump Inhibitors in Observational Studies: A Systematic Review and Meta-Analysis, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.