TISSUE PROSTAGLANDIN LEVELS IN FAMILIAL ADENOMATOUS POLYPOSIS PATIENTS TREATED WITH SULINDAC

BACKGROUND: Recent work has demonstrated a correlation between frequen cy of aspirin ingestion and colorectal cancer prevention. Sulindac, an other nonsteroidal anti-inflammatory drug (NSAID), has been shown to c ause polyp regression and a fall in cell proliferation in patients wit h familial adenomatous polyposis, who are destined to develop colorect al cancer unless the colon is removed. However, the mode of action of NSAIDs in colorectal carcinogenesis prevention remains to be determine d, although a prostaglandin-mediated mechanism seems likely. METHODS: Rectal or duodenal biopsies from 20 patients with familial adenomatous polyposis, who had been randomized to sulindac or placebo, were analy zed for prostaglandin (PG) E(2) and F-2 alpha levels before and after treatment. RESULTS: A significant fall in prostaglandin E(2) and F-2 a lpha levels was seen in patients who were on sulindac; this correlated with a visual improvement in number and size of polyps in the same pa tients (P = 0.0096; PGE(2), P = 0.036; PGF(2 alpha), Spearman's rank c orrelation). CONCLUSIONS: Nonsteroidal antiinflammatory drugs may prev ent colorectal cancer by their inhibition of prostaglandin synthesis. Prostaglandins may be implicated in carcinogenesis through an increase in cell proliferation, through immunosuppression, by increasing neova scularization, or via a mutagenic effect.