Epidemiologic and clinical research has revealed many risk factors which, taken together, can help estimate a person’s probability of developing esophageal adenocarcinoma (EAC). These include:
- demographic factors,
- host and lifestyle factors,
- medications, family history, and
- genetic markers.
In the general population, symptomatic gastroesophageal reflux (sGERD), obesity, cigarette smoking, and family history of BE or EAC are the major factors associated with increased risk.1–6 Conversely, physical activity, use of non-steroidal anti-inflammatory drugs (NSAIDs) and statin drugs have been associated with decreased risk in observational studies and randomized clinical trials.7–11Many of these factors are thought to affect EAC risk through the exacerbation (or reduction) in inflammation (figure 1.)
It is important to note that while the observational studies are generally very consistent in finding the above associations, they are not necessarily causal, and no randomized clinical trials have examined the extent to which behavioral change (e.g., losing weight, quitting smoking) actually affects risk of esophageal adenocarcinoma. In contrast, a number of clinical trials have reported on reduced risk associated with statin use, although esophageal cancer was not the primary endpoint. A recent trial11 of use of aspirin and/or a proton pump inhibitor did find a suggestion (not quite statistically significant) that aspirin might be effective, especially along with proton pump inhibitors; this finding is supported by a number of observational studies.
Regarding other potential risk factors, a strong body of epidemiologic evidence suggests that infection with Helicobacter pylori is associated with an approximately 50% decreased risk of EAC,12 although the mechanism(s) remain unclear. Similarly, there is some evidence from observational studies that diet, in particular higher intake of fat and lower intake of fruits and vegetables, is associated with increased EAC risk.13. Finally, while almost two dozen genetic loci have been identified as associated with EAC risk,15 as a whole, their added discriminatory ability is still rather modest, especially compared to family history.16,17
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