The potential benefits of statin therapy may extend to prevention of esophageal cancer, according to a study reported here.

A meta-analysis of 13 studies showed a 28% reduction in the odds of esophageal cancer and a 41% lower risk of esophageal adenocarcinoma in the subset of patients with Barrett’s esophagus.

The chemopreventive benefits were even greater among patients who were using aspirin or nonsteroidal anti-inflammatory drugs in addition to statins, Siddharth Singh, MD, said at the American College of Gastroenterology meeting.

“We believe that statins may decrease the risk of esophageal cancer [overall] and in a subset of patients with Barrett’s esophagus who are at high risk for esophageal adenocarcinoma,” said Singh, of the Mayo Clinic in Rochester, Minn. “Future randomized trials in patients at high risk of esophageal adenocarcinoma are warranted.”

Several lines of evidence have supported a biologic rationale for a chemopreventive effect of statins on esophageal cancer. As a class, the drugs have immunomodulatory, anti-inflammatory, and proapoptic activity, all of which could have a chemopreventive effect on cancer.

Data from preclinical and observational studies had suggested a chemopreventive effect of statins against esophageal cancer, but the results of individual investigations lacked consistency. To address that issue, Singh and colleagues performed a systematic review and meta-analysis.

Investigators searched several databases for observational studies and randomized trials that have examined statins’ relationship to esophageal cancer. The search extended through August 2012 and employed three principal criteria to identify studies to include in their meta-analysis: clearly defined and evaluated exposure to statins; reported outcomes for esophageal cancer; and provided odds ratios or risk ratios, or reported data to calculate estimates.

The primary outcome for the analysis was risk of esophageal cancer. The secondary outcome was the risk of esophageal adenocarcinoma or high-grade dysplasia in patients with Barrett’s esophagus.

The search yielded 13 studies involving a total of 1,132,969 participants and approximately 9,285 cases of esophageal cancer, including 312 cases of Barrett’s esophagus among 2,125 patients in the studies looking at that condition. Six investigations originated in North America, five in Europe, one in Asia, and one was a multicenter study. Most of the studies reported findings adjusted for major covariants, such as body mass index and smoking status.

Singh said six of the 13 studies showed significant associations between statin use and a reduced risk of esophageal cancer. Overall, the meta-analysis produced an odds ratio of 0.72 for statin use versus no use, representing a 28% reduction in cancer risk.

The investigators found substantial heterogeneity among the studies, which they traced to differences in the method of ascertaining statin exposure. They performed another analysis limited to high-quality studies, and the results did not change substantively.

Five trials reported data on the relationship between statin use and the odds of developing esophageal adenocarcinoma or high-grade esophageal dysplasia in patients with Barrett’s esophagus. Four of the trials yielded significant associations, resulting in a 41% reduction in the odds for the secondary endpoint.

Acknowledging limitations of the study, Singh said investigators had little information about the dose or duration of statin therapy, and the optimal timing of statin use remained unclear. Additionally, the studies included in the analysis provided limited information about histologic types of esophageal cancer.

During the discussion that followed the presentation, Singh said an even larger chemopreventive effect was observed in the patients with Barrett’s esophagus who were also taking aspirin regularly.

An unidentified member of the audience asked how the investigators separated the chemopreventive effect of statins in patients who were taking proton pump inhibitors (PPIs), which also have been shown to reduce the risk of esophageal cancer. Singh responded that a similar effect of PPI use would have been expected in the cases and controls, so that the separate chemopreventive activity of statins could be ascertained.

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Primary source: American College of Gastroenterology
Source reference: Singh S, et al “Statins and the risk of esophageal cancer: A systematic review and meta-analysis” ACG 2012.