Tissue prostaglandin levels in familial adenomatous polyposis patients treated with sulindac.
BACKGROUND
Recent work has demonstrated a correlation between frequency of aspirin ingestion and colorectal cancer prevention. Sulindac, another nonsteroidal anti-inflammatory drug (NSAID), has been shown to cause polyp regression and a fall in cell proliferation in patients with familial adenomatous polyposis, who are destined to develop colorectal cancer unless the colon is removed. However, the mode of action of NSAIDs in colorectal carcinogenesis prevention remains to be determined, 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 analyzed for prostaglandin (PG) E2 and F2 alpha levels before and after treatment.


RESULTS
A significant fall in prostaglandin E2 and F2 alpha levels was seen in patients who were on sulindac; this correlated with a visual improvement in number and size of polyps in the same patients (P = 0.0096; PGE2, P = 0.036; PGF2 alpha, Spearman's rank correlation).


CONCLUSIONS
Nonsteroidal anti-inflammatory drugs may prevent colorectal cancer by their inhibition of prostaglandin synthesis. Prostaglandins may be implicated in carcinogenesis through an increase in cell proliferation, through immunosuppression, by increasing neovascularization, or via a mutagenic effect.
Nugent
K P
KP
St. Mark's Hospital, Northwick Park, Harrow, Middlesex, United Kingdom.
Spigelman
A D
AD
Phillips
R K
RK
D011125:Adenomatous Polyposis Coli / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001706:Biopsy; D015237:Dinoprost / Q000276:immunology / Q000378:metabolism*; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D012074:Remission Induction; D013467:Sulindac / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013467:Sulindac; D015237:Dinoprost; D015232:Dinoprostone