doi: 10.1158/1940-6207.CAPR-20-0274. Online ahead of print.
Association of common use pharmaceuticals in reducing risk of esophageal adenocarcinoma: A SEER-Medicare analysis
Holli A Loomans-Kropp , Matthew Chaloux , Ellen Richmond , Asad Umar
Barrett's esophagus (BE), a recognized risk factor for esophageal adenocarcinoma (EAC), is routinely managed with proton pump inhibitors (PPIs) when symptomatic. Several lines of evidence suggest that PPIs may prevent malignant transformation. Chronic use of other common drugs, namely statins, nonsteroidal anti-inflammatory drugs (NSAIDs) and metformin, may also interfere with BE carcinogenesis, but confirmatory evidence is lacking. We identified 1,943 EAC cases and 19,430 controls (matched 10:1) between 2007 and 2013 that met our specified inclusion criteria in the SEER-Medicare database. conditional logistic regression was used to generate odds ratios (ORs) and 95% confidence intervals (95% CI). Wald x2 tests were used to assess significance of covariates. Compared to controls, EAC cases had a higher prevalence of BE (26.2%). Use of PPIs, NSAIDs, statins, or metformin reduced the odds of EAC (PPIs: 0.10, 95% CI 0.09, 0.12; NSAIDs: 0.62, 95% CI 0.51, 0.74; statins: 0.15, 95% CI 0.13, 0.17; metformin: 0.76, 95% CI 0.62, 0.93). When stratified by BE, these associations persisted, though no association was found between NSAID use and EAC risk for participants with BE. Dual use of PPIs with NSAIDs, or statins, and NSAID, statin, or metformin use alone also showed significant EAC risk reduction among all participants and those without BE. Use of PPIs alone, and with NSAIDs, statins, or metformin was associated with reduced risk of EAC, however history of BE may diminish drug efficacy. These results indicate that common pharmacologic agents alone or in combination may decrease EAC development.