Statin use is associated with a reduction in the incidence of esophageal adenocarcinoma: a case control study

Abstract

The incidence of esophageal adenocarcinoma (EAC) is increasing significantly throughout the developed world. As yet, there are no proven chemopreventive strategies. In laboratory studies, aspirin, non-steroidal anti-inflammatory drugs and statins have promising chemopreventive actions. Several observational studies support a protective effect of aspirin and non-steroidal anti-inflammatory drugs, but there are only limited clinical data exploring the potential protective effect of statins. We conducted a case-control study examining aspirin and statin use in patients with EAC. Cancer cases were compared against age-sex-matched controls attending for diagnostic upper gastrointestinal endoscopy. Risk factor and drug exposure were established using standardized interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. A total of 112 cases and 448 controls were enrolled. Statin use was associated with a significantly lower incidence of EAC (odds ratio 0.52, 95% confidence interval 0.27-0.92). Aspirin use was also associated with apparent protection against EAC (odds ratio 0.68, 95% confidence interval 0.28-0.92), and a significantly greater effect was seen with the combination of statin plus aspirin (odds ratio 0.27, 95% confidence interval 0.05-0.67). There was a significant trend for greater risk reduction with longer duration and higher doses of statin use. Simvastatin comprised the majority of statin use, but similar effects were seen with simvastatin and non-simvastatin agents. In this observational study, patients regularly using statins or aspirin had a lower incidence of EAC. Statins may have clinically useful effects in preventing the development of EAC.

Reduced Risk of Barrett’s Esophagus in Statin Users: Case–Control Study and Meta-Analysis

“…The main strengths of our study are the accurate and full records of medication exposure as reported previously (14,15,23) and the ability to correlate this with clearly defined endoscopic findings within the context of an adequately powered study. The main weakness, inherent in any observational study, is that of uncorrected bias.…”

“…The differences between the groups were quantified using the calculated odds ratios and 95% confidence intervals, with the significance level set at P < 0.05. Unconditional logistic regression was used to correct for potentially confounding 8 factors: age, smoking, alcohol use, body mass index, waist circumference and all prescribed and over the counter mediations recorded (14,15,19).…”

“…Controls and cases were recruited as part of a larger project examining risk and prognostic factors for gastrointestinal diseases (14,15,19). All subjects were planned to undergo their first ever gastroscopy.…”

“…All subjects were planned to undergo their first ever gastroscopy. All subjects were interviewed by trained interviewers immediately preceding their endoscopy as previously reported (14,15,19). The standardised interview included demographic and social details, prescribed and over-the-counter medicine use.…”

“…Statins inhibit proliferation, induce apoptosis and inhibit growth factor signalling in Barrett's cell lines (10,11) and whilst COX-pathway inhibitors also have experimental anticancer effects, these are additive to those of statins (10)(11)(12). Several observational studies and two metaanalyses (13)(14)(15)(16)(17) have reported that statin use is associated with a lower rate of progression to cancer in patients with Barrett's oeosphagus and again this effect is significantly enhanced in combination with aspirin (16). In a meta-analysis, pooled adjusted odds ratios showed that statin use in the Barrett's population was associated with a 43% reduction in the risk of malignant progression (OR = 0.57 (95% CI 0.43-0.75)) and this effect was even more pronounced in those concurrently using low-dose aspirin (OR 0.26 (95% CI 0.1-0.68)) (16).…”