Association between proton pump inhibitors use and risk of gastric cancer in patients with GERD

Long-term proton pump inhibitors use and risk of gastric cancer: a meta-analysis of 926 386 participants

“…We found that participants with long-term PPIs use had approximate twofold risks with GC (OR 2.10; 95% CI 1.10 to 3.09; I 2 =97.3%; P heterogeneity  <0.001), and this result was similar to the studies by Cheung et al 1 and Peng et al 2. Subgroup analysis indicated that the subgroup of ‘Asian’, ‘non-cardia GC’, ‘case–control study’ and ‘participants without Helicobacter pylori infection’ showed significantly increased GC risk, while subgroup of ‘Caucasian’, ‘cardia GC’, ‘cohort study’ and ‘participants with Helicobacter pylori infection’ did not have statistically significant results.…”

Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract—evidence from next‐generation sequencing studies

“…17 Two population-based case-control studies from Taiwan demonstrated increased odds for any-site gastric cancer in patients who were treated at least two times for gastro-oesophageal reflux disease between 1996 and 2011 (OR 2.48, 95% CI 1.92-3.20) and in subjects with a cumulative duration of PPI treatment of >6 months for unknown indications between 2000 and 2013 (OR 2.00, 95% CI 1.36-2.95), each compared with those who never used PPIs. 18,19 A recent meta-analysis including >900 000 individuals confirmed this association with a pooled OR of 2.10 (95% CI 1.10-3.09) and the previously reported duration-response relationship 20 (Table 1, Figure 2). To date, the possible biological mechanisms underlying this association are unclear.…”

“…Systematic review of 10 studies including three RCTs 104 Gastric cancer 2a Increased gastric cancer risk among long-term PPI users in large observational cohort studies and one meta-analysis (pooled OR 2.10, 95% CI 1.10-3.09). Probable confounding [16][17][18][19][20] Gastrointestinal infections and microbiome alterations…”

“…PPIs can induce bacterial overgrowth of the stomach and longterm PPI use has been associated with increased risk for gastric cancer in observational studies of large patients cohorts. [16][17][18][19][20] Indeed, gastric microbes are believed to contribute to gastric carcinogenesis: Non-H pylori bacterial overgrowth and H pylori were shown to independently and synergistically accelerate the development of atrophic gastritis 92 and in the H pylori INS-GAS mouse model, the gastric commensal microbiota were shown to contribute to carcinogenesis. 93,94 Two human populations with high and low gastric cancer risk in Colombia showed marked differences in gastric microbiota compositions.…”

“…Continuation of PPI therapy after Helicobacter pylori eradication in the population of Hong Kong was associated with an increased risk for non‐cardia gastric cancer during a median follow‐up of 7.6 years (HR 2.44, 95% CI 1.42‐4.20) . Two population‐based case–control studies from Taiwan demonstrated increased odds for any‐site gastric cancer in patients who were treated at least two times for gastro‐oesophageal reflux disease between 1996 and 2011 (OR 2.48, 95% CI 1.92‐3.20) and in subjects with a cumulative duration of PPI treatment of >6 months for unknown indications between 2000 and 2013 (OR 2.00, 95% CI 1.36‐2.95), each compared with those who never used PPIs . A recent meta‐analysis including >900 000 individuals confirmed this association with a pooled OR of 2.10 (95% CI 1.10‐3.09) and the previously reported duration–response relationship (Table , Figure ).…”