Nonsteroidal Anti-inflammatory Drugs and the Esophageal Inflammation-Metaplasia-Adenocarcinoma Sequence

Abstract

Observational studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of esophageal adenocarcinoma, but it is not known at what stage they may act in the esophageal inflammation-metaplasia-adenocarcinoma sequence. In an all-Ireland case-control study, we investigated the relationship between the use of NSAIDs and risk of reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Patients with esophageal adenocarcinoma, long-segment Barrett's esophagus and population controls were recruited from throughout Ireland. Esophagitis patients were recruited from Northern Ireland only. Data were collected on known and potential risk factors for esophageal adenocarcinoma and on the use of NSAIDs, including aspirin, at least 1 year before interview. Associations between use of NSAIDs and the stages of the esophageal inflammationmetaplasia-adenocarcinoma sequence were estimated by multiple logistic regression. In total, 230 reflux esophagitis, 224 Barrett's esophagus, and 227 esophageal adenocarcinoma and 260 population controls were recruited. Use of aspirin and

Nonsteroidal Anti-inflammatory Drugs and Risk of Esophageal and Gastric Adenocarcinomas in Los Angeles County

“…Infection with Helicobacter pylori, Barrett's esophagus, hiatal hernia, and reflux symptoms are independent risk factors for esophageal and gastric adenocarcinomas in this study population (14,23,24). Presence of these and other UGI conditions can influence the use of NSAIDs (39); in fact, for several of these conditions, NSAID use is contraindicated.…”

“…Most previous studies of the relationship between NSAID use and risk of esophageal or gastric cancer have defined the reference group as individuals whose NSAID use history falls below a certain threshold (14,15,20,21,38,41,42), similar to our approach where the reference group consisted of individuals whose had never used at least two NSAID pills per week for 1 month. Two studies have separated irregular users from never users (22,37), but neither separated adenocarcinomas of the esophagus from squamous cell carcinomas nor did either study segregate gastric cancers by site.…”

“…Recent studies have shown that NSAID use reduces the risk of esophageal adenocarcinoma (11)(12)(13)(14)(15)(16). Three recent metaanalyses that included both case-control studies and cohort studies indicated that aspirin and other NSAID users were at reduced risk of esophageal squamous cell carcinoma, esophageal adenocarcinoma, and noncardia gastric adenocarcinoma but not at reduced risk of gastric cardia cancers (17)(18)(19).…”

Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis

“…We limited our analysis to papers reporting case -control or cohort studies of the association between the use of either aspirin or non-aspirin NSAIDS and the risk of oesophageal or gastric adenocarcinomas. We included the following studies for the oesophagus (Farrow et al, 1998;Cheng et al, 2000;Lindblad et al, 2005;Anderson et al, 2006;Jayaprakash et al, 2006;Ranka et al, 2006;Fortuny et al, 2007;Duan et al, 2008;Sadeghi et al, 2008), cardia (Farrow et al, 1998;Zaridze et al, 1999;Akre et al, 2001;Fortuny et al, 2007;Duan et al, 2008;Sadeghi et al, 2008), non-cardia (Farrow et al, 1998;Zaridze et al, 1999;Akre et al, 2001;Fortuny et al, 2007;Duan et al, 2008), and gastric NOS (Thun et al, 1993;Schreinemachers and Everson, 1994;Coogan et al, 2000;Langman et al, 2000;Akre et al, 2001;Sorensen et al, 2003;Ratnasinghe et al, 2004;Lindblad et al, 2005) and excluded a few studies from certain sections that did not specify the agent (Garidou et al, 1996;Suleiman et al, 2000) or the histology of the oesophageal tumours (Funkhouser and Sharp, 1995;Langman et al, 2000). Two other studies, one prospective and one retrospective, reported on the association between aspirin and oesophageal adenocarcinoma, but included only subjects with Barrett's oesophagus in the reference group (Tsibouris et al, 2004;Vaughan et al, 2005) and these pap...…”

Histone deacetylases and the immunological network: implications in cancer and inflammation

“…This response has been also implicated in the initiation and progression of cancer (de Visser and Coussens, 2005;Khan and Tomasi, 2008). For instance, some malignancies may be prevented by the use of anti-inflammatory drugs (Anderson et al, 2006;Rigas, 2007). Inhibition of certain proinflammatory cytokines has also been shown to decrease the aggressiveness of some tumor types Abbreviations: GM-CSF, granulocyte-macrophage colony-stimulating factor; HDAC, histone deacetylase; IFN, interferon; IL, interleukin; NF-kB, nuclear factor-kB.…”