| Summary: | Evidence from animal and in vitro studies indicates that n-3 fatty acids may inhibit carcinogenesis, and epidemiological studies suggest a reduced risk of oesophageal cancer in populations with high consumption of fish. One of the possible mechanisms for this chemopreventive effect is the suppression of eicosanoid production through inhibition ofthe enzyme cyclo-oxygenase (COX)-2. The major predisposing factor for the development of oesophageal adenocarcinoma is the replacement of normal squamous epithelium by columnar lined epithelium, also known as Barrett's oesophagus. Individuals with this condition have a thirty to forty fold-increased risk of developing oesophageal adenocarcinoma compared to the general population. In this study, the effects of dietary supplementation with the n-3 fatty acid eicosapentaenoic acid (EPA) on tissue eicosanoid levels (PGE2 and LTB4) and cyclo-oxygenase-2 (COX2) activity in Barrett's oesophagus have been determined. Methods Fifty-two participants with known Barrett's oesophagus agreed to take part in this study. Six participants withdrew during the study period. Endoscopic biopsies were obtained from a recorded level within the area ofBarrett's, and then 27 randomly assigned patients consumed EPA capsules (1.5g/day) for six months, the others acting as controls. At the end ofthis period, patients were re-endoscoped and biopsies taken at the same level. Tissue samples were analysed for mucosal lipid profile, PGE2, LTB4, COX-2 protein and RNA levels. Levels of cellular proliferation were also measured by Ki-67 immunohistochemistry. Supplied by The British Library - 'The world's knowledge' /-y 3 Results There was a significant increase in mucosal EPA content after dietary supplementation (6 months vs. baseline: 2.4% vs. 0.8% of total lipid content~ p<O.OOl). After EPA supplementation, there was a significant reduction in levels ofCOX-2 protein in Barrett's biopsies as measured by immunoblotting (p<O.05) but no change in COX-2 RNA levels. Levels ofPGE2 and LTB4 were well correlated between biopsies (r=O.6 p<O.Ol) but supplementation had no influence on these levels or on Ki-67 activity as measured by immunohistochemistry. Conclusion In this study, supplementation with EPA significantly altered the proportions ofn-3 fatty acids and reduced COX-2 levels in Barrett's tissue. However, total eicosanoid levels and proliferative activity remained unchanged - any chemopreventive effect of fish oils is likely to be independent of these mechanisms.
|
|---|
