Systematic review: potential preventive effects of statins against oesophageal adenocarcinoma.
BACKGROUND
The incidence of oesophageal adenocarcinoma (OAC) has risen dramatically in recent decades, and its prognosis remains extremely poor. There is emerging evidence that statins may prevent OAC.


OBJECTIVE
To systematically review both the experimental and epidemiological evidence to determine whether statins reduce the risk of developing OAC.


METHODS
Relevant laboratory and epidemiological studies were identified by systematically searching the PUBMED and EMBASE electronic databases for data on statins and oesophageal cancer (OC). The evidence was assessed according to the nine Bradford Hill criteria (BHC) of causality. Pooled effect sizes (ES) were calculated for the risk of OC with prior statin use.


RESULTS
Many of the BHC were supported including: 'plausible biological mechanisms', 'coherence', 'strong associations', 'consistency', 'biological gradient', 'analogy' and 'temporality'. Three experimental studies reported that statins inhibited proliferation, induced apoptosis and may limit metastatic potential in OAC cell lines. Fixed effects meta-analysis of two prospective studies in Barrett's oesophagus cohorts, involving 1382 participants, showed an ES of 0.53 (95% CI = 0.36-0.78, P = 0.001, I(2)  = 0%) for risk of OAC with prior statin use. Meta-analysis of three prospective studies in general population cohorts, involving 35 214 participants, showed an ES of 0.86 (95% CI = 0.78-0.94, P = 0.001, I(2)  = 0%) for risk of OC with prior statin use. The most important criterion, 'experiment', is as yet unfulfilled as to date there are no clinical trials which investigate this hypothesis.


CONCLUSIONS
There is some evidence that statins may protect against the development of OAC, although to be conclusive, data from randomised clinical trials are required.
Norwich Medical School, University of East Anglia, Norwich, UK. Leo.Alexandre@uea.ac.uk
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L
Alexandre
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Clark
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Cheong
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Lewis
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Hart
D000230:Adenocarcinoma / Q000517:prevention & control*; D004938:Esophageal Neoplasms / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors