Table III.
Association between PPIs and risk of gastrointestinal cancer in subgroup meta-analyses using a random-effects model.
| Factors | No. of studies | Summary OR/RR/HR (95% CI) | Heterogeneity, I2 (%) | (Refs.) |
|---|---|---|---|---|
| All studies | 23 | 2.09 (1.78–2.46) | 98.0 | (27–49) |
| Type of cancer | ||||
| Esophageal cancer | 2 | 2.44 (1.61–3.70) | 49.6 | (27,37) |
| Gastric cancer | 11 | 2.88 (2.29–3.61) | 97.4 | (28,30,32,33,37,41,44–47,49) |
| Pancreatic cancer | 3 | 1.80 (1.34–2.42) | 88.6 | (34,40) |
| Colorectal cancer | 4 | 1.15 (0.85–1.54) | 88.9 | (31,39,43,48) |
| Liver cancer | 3 | 1.55 (1.17–2.06) | 67.2 | (35,36,38) |
| Gallbladder cancer | 1 | 1.58 (1.37–1.81) | N/A | (42) |
| Extrahepatic bile ducts cancer | 1 | 1.17 (1.56–2.00) | N/A | (42) |
| Intrahepatic bile ducts cancer | 1 | 1.88 (1.57–2.33) | N/A | (42) |
| Sex | ||||
| Male | 11 | 1.70 (1.36–2.12) | 98.1 | (30,31,34,35,38,40,41,42,46–48) |
| Female | 10 | 1.84 (1.55–2.19) | 96.1 | (30,31,34,38,40,41,42,46–48) |
| Age (≥50 years) | 7 | 1.76 (1.41–2.20) | 97.7 | (30,31,34,38,40,42,46) |
| Obesity | 3 | 1.14 (1.01–1.27) | 0 | (31,34,35) |
| Smoking | 4 | 1.11 (0.98–1.27) | 65.8 | (31,34,35,47) |
| Type of PPIs | ||||
| Omeprazole | 4 | 1.32 (0.96–1.80) | 69.4 | (41,43,47,48) |
| Lansoprazole | 4 | 1.42 (0.99–2.06) | 81.1 | (41,43,47,48) |
| Pantoprazole | 3 | 1.08 (0.91–1.28) | 0 | (43,47,48) |
| Esomeprazole | 3 | 1.17 (0.70–1.96) | 72.6 | (43,47,48) |
| Rabeprazole | 3 | 1.09 (0.77–1.56) | 51.6 | (43,47,48) |
| Duration of PPI use | ||||
| ≤1 year | 4 | 5.23 (2.96–9.24) | 99.6 | (30,37,40,42) |
| 1-3 years | 10 | 1.72 (1.44–2.07) | 86.8 | (30,33,37,40,42,43–45,47,48) |
| 3-5 years | 6 | 1.17 (0.96–1.43) | 79.5 | (27,30,33,37,40,43) |
| >5 years | 4 | 1.16 (0.74–1.84) | 96.6 | (30,37,40,42) |
| Concurrent medication | ||||
| Aspirin | 3 | 1.09 (1.01–1.18) | 0 | (31,38,47) |
| Statins | 4 | 0.85 (0.69–1.06) | 56.5 | (31,35,38,47) |
| Region | ||||
| America | 3 | 1.09 (0.55–2.17) | 86.3 | (27,35,39) |
| Asia | 9 | 1.45 (1.17–1.80) | 79.8 | (31,33,34,38,43–46,49) |
| Europe | 11 | 1.93 (1.51–2.45) | 98.3 | (28–30,32,36,37,40–42,47,48) |
| Study design | ||||
| Retrospective cohort | 10 | 2.60 (1.88–3.60) | 97.6 | (27,28,30,32,33,38,43–46) |
| Prospective cohort | 13 | 1.71 (1.41–2.08) | 97.9 | (29,31,34–37,39–42,47–49) |
| Methodological quality | ||||
| High quality | 13 | 1.43 (1.20–1.70) | 78.2 | (28,31,33,34,36,41,43–49) |
| Low quality | 10 | 2.61 (2.20–3.09) | 98.0 | (27,29,30,32,35,37–40,42) |
PPI, proton pump inhibitor; OR, odds ratio; RR, relative risk; HR, hazard ratio.