Dietary fat, arachidonic acid metabolism and lipid peroxidation have all been implicated in colorectal carcinogenesis. Fatty acids, prostaglandins (PGE,, PGF,,) and malondialdehyde O A ) , the stable end-product of lipid peroxidation of polyunsaturated fatty ad& (PUFAs), were studied in paired tumour and normal m u m a of 20 patients with colorectal cancer. Levels of arachidonic acid and total PUFAs were increased in the phospholipid fraction of tumours (P<@OS). Levels of PGE, and MDA were also ~ higher in tumours (P<o.OOl) and there was a significant correlation between M D A and PGE, concentrations (rs = 0.69, P <0.01). In contrast to previously reported In vitro studies, this work suggests that lipid peroxidation may be enhanced in human colorectal tumours. As PGEl and M D A have been shown to be involved in cardnogenesis, thege m a y be considered potential therapeutic targets for preventing or treating colorectal carcinoma.
Colorectal carcinoma is the second most common cause of death from cancer in westernized countries1. Epidemioand e~perimental~-~ studies indicate that diets high in saturated fat promote colorectal carcinoma, whereas the effects of dietary n-6 unsaturated fats are less ~l e a r ~J -~~.
In contrast, dietary n-3 fats are protectivell-lZ or even thera-pe~tic"9~~. Possible mechanisms accounting for these differing effects include direct luminal activityI5, alteration of bile acid metabolism4, changes in immunitylh, effects on lipid peroxidation" and modulation of prostaglandin synthesid8. Interest in prostaglandins has recently heightened after reports that aspirin and other non-steroidal antiinflammatory drugs (NSAIDs) may reduce the incidence and mortality rate from colorectal cancer1Y-21, and induce polyp regression in patients with familial adenomatous polyposis (FAP)zz-2h. Arachidonic acid (20:4, n-6), levels of which are increased in the total lipid extract from humanz7 and experi-mentalz8 colorectal tumours, is the precursor for the series 2 prostaglandins implicated in immune suppressionzY and the promotion of metastasisM. Moreover, raised PGE, levels occur in colorectal t u m 0 ~r s ~~J ~.
Lipid peroxidation may have a role in carcin~genesis'~.
There may be an inverse correlation between tissue lipid peroxidation and antioxidant levels, although the experimental data are c~nflicting~~-~~. The stimulation of