Guangdong Provincial People's Hospital Guangzhou, Guangdong, China (People's Republic)
Award: Presidential Poster Award
Ruijie Zeng, MBBS1, Felix Leung, MD2, Weihong Sha, MD1, Hao Chen, MD1 1Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China; 2University of California Los Angeles, Los Angeles, CA
Introduction: Recent reports suggested that PPI increased the risk of digestive tract cancers, which continued to perpetuate concerns over the safety of PPI use. We performed a systemic review and meta-analysis to assess the effect of PPI use on digestive tract cancers with a comprehensive evaluation by Bradford Hill criteria of causation.
Methods: We searched Medline, Embase, and Web of Science databases for observational studies published up to Jan 15th, 2021. Random effects models were used to estimate pooled relative risks (RRs). Restricted cubic spline and fractional polynomial models were used to investigate the cumulative defined daily dose (cDDD)- and duration-risk relationships. Bradford Hill Criteria of causation were utilized to assess causation. PROSPERO Registration: CRD42020211103.
Results: Thirty-two publications containing 4.3 million participants were included in our study. PPI use is associated with an increased risk of overall digestive tract cancers (RR = 1.63, 95% confidence interval 1.33 to 2.00). PPI use is correlated with increased risks of gastric cancer (RR = 1.78, 95% confidence interval 1.38 to 2.31), pancreatic cancer (RR = 1.72, 95% confidence interval 1.05 to 2.82) and liver cancer (RR = 1.62, 95% confidence interval 1.04 to 2.52), but not of esophageal cancer (RR = 2.06, 95% confidence interval 0.65 to 6.57) and colorectal cancer (RR = 1.24, 95% confidence interval 0.93 to 1.66). The association between PPI and digestive tract cancers is stronger in people with minimal exposure. The risks decline and become non-significant as cDDD or duration increases. Evaluation by Bradford Hill Criteria demonstrates weak evidence of causation.
Discussion: Early symptoms of gastric, liver and pancreatic cancers are non-specific. These incipient symptoms, including abdominal pain, heartburn, nausea and vomiting, mimic acid reflux and lead to the empiric treatment with PPIs before the eventual diagnosis of digestive tract cancers. Therefore, the significant associations between PPI dose/duration and cancer risks are indicative of coincidence rather than causality. Through comprehensive evaluation, the causality between PPI use and digestive tract cancers is not supported by the evidence in the current study. Concerns over carcinogenic side-effects of PPI might be unfounded. Dose-response analysis and Bradford Hill’s Criteria are strongly recommended to interpret such data in future studies.
Disclosures: Ruijie Zeng indicated no relevant financial relationships. Felix Leung indicated no relevant financial relationships. Weihong Sha indicated no relevant financial relationships. Hao Chen indicated no relevant financial relationships.
Ruijie Zeng, MBBS1, Felix Leung, MD2, Weihong Sha, MD1, Hao Chen, MD1. P3078 - An Unfounded Concern - Proton Pump Inhibitors and Risk of Digestive Tract Cancers: A Systemic Review and Meta-Analysis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.