Aspirin and Nonsteroidal Anti-Inflammatory Drug Use and the Risk of Barrett’s Esophagus

Abstract

Background The use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of esophageal adenocarcinoma; however, it is unknown where these agents may act in the proposed pathway from normal mucosa to Barrett’s esophagus to esophageal adenocarcinoma. Aim To evaluate the association between aspirin and NSAID use and Barrett’s esophagus in a case-control study within a large community-based population. Methods We conducted a case-control study of aspirin/NSAID use and Barrett’s esophagus within the Kaiser Permanente Northern California population. Cases had a new diagnosis of Barrett’s esophagus between October 2002 and September 2005; controls were members without a diagnosis of Barrett’s esophagus. Aspirin/NSAID “users” were persons with at least weekly use of either aspirin or NSAIDs in the year prior to the index date. Results Persons with Barrett’s esophagus were less likely to use aspirin than population controls (odds ratio [OR]=0.59, 95% confidence interval [CI] 0.39–0.87); a stronger association was found among cases and controls with reflux symptoms (OR=0.49, 95% CI 0.32–0.75; p-value interaction=0.004). Similar associations were found with use of either aspirin and/or non-aspirin NSAIDs) (OR= 0.53, 95% CI 0.35–0.81), although NSAID use alone was not significantly associated with Barrett’s esophagus (OR=0.74, 95% CI 0.47–1.16). The strength of the association was highest among persons with at least moderate to high total medication intake. Conclusions Regular use of aspirin or NSAIDs was associated with a decreased risk of Barrett’s esophagus, particularly among persons with GERD symptoms. These findings have implications for chemoprevention, as some of the previously described protective association between aspirin/NSAIDs and esophageal adenocarcinoma may be explained by events that occur prior to the development of Barrett’s esophagus.

Nonsteroidal Anti-Inflammatory Drug Use is Not Associated With Reduced Risk of Barrett’s Esophagus

“…The individual study ORs may differ somewhat from the pooled ORs due to differences in confounding structure. For example, race was a strong confounder of the association between NSAID use and risk of Barrett's esophagus in KPNC (14). Here, we limited the analyses to non-Hispanic white study participants.…”

“…The six studies were as follows: the Houston Barrett's Esophagus study (based at the Michael E. DeBakey VA Medical Center at Houston, TX; hereafter “Houston”) (17); the Factors Influencing the Barrett's/Adenocarcinoma Relationship study (based in Ireland; “FINBAR”) (13); the Epidemiology and Incidence of Barrett's Esophagus study (based in the Kaiser Permanente Northern California population; “KPNC”) (14); The Newly Diagnosed Barrett's Esophagus Study (based at the University of Michigan and Ann Arbor Veterans Affairs Medical Center at Ann Arbor, MI; “NDB”) (18); the Study of Digestive Health (based in Brisbane, Australia; “SDH”) (16); and the Study of Reflux Disease (based in western Washington State; “SRD”) (19). We additionally restricted our analyses to non-Hispanic white study participants due to low numbers of cases from non-white ethnic groups (total n=95; range n=17 in NDB to n=43 in KPNC).…”

“…Five of the six studies asked about “regular use” of medications over a specified time period with a minimum frequency of use (13,14,17-19). The duration of regular use varied across the five studies, from 3 months to 1 year of use.…”

Aspirin Use is Associated with Lower Risk of Barrett's Esophagus in Women

“…Our results are consistent with two prior hospital-and population-based retrospective case-control studies which also observed an inverse association between regular aspirin use and BE, especially for higher doses, but not between non-aspirin NSAIDs and BE. 31,32 In contrast to these results, a recent pooled analysis of data from six case-control studies in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), found no association between regular aspirin use and BE when compared to either population or GERD controls. Similar null findings were reported for non-aspirin NSAIDs and any NSAIDs.…”

“…30 Human data regarding the association of aspirin and BE development are scant and conflicting, especially for women. Some observational studies, 17,31,32 but not all, [33][34][35][36] suggest that aspirin, but not NSAIDs, may reduce the onset of BE. Notably, a recent pooled analysis of six studies, which included 1,474 BE patients and 4,274 controls, saw no significant association between aspirin/NSAIDs and BE.…”