Nonsteroidal anti-inflammatory drugs, apoptosis, and colorectal adenomas.
OBJECTIVE
Observational studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal neoplasia. The mechanism of this effect could be via modification of apoptotic activity in colonic mucosa. We examined grossly normal rectal mucosa in patients with adenomas and adenoma-free controls to assess the associations between NSAID use, adenomatous polyps, and apoptosis.


METHODS
Study participants were drawn from consecutive patients who underwent colonoscopy between August, 1998, and February, 2000. Biopsy specimens were taken from normal-appearing rectal mucosa 10 cm from the anal verge. Apoptosis was scored from coded, H&E-stained sections using morphologic methods. Proliferation was scored using whole crypt mitotic counts. Univariate and multivariate regression analyses were conducted to estimate crude and adjusted odds ratios (ORs).


RESULTS
There were 226 patients with adenomas and 493 adenoma-free controls. After adjusting for sex, age, race, and body mass index (BMI), individuals in the highest tertile of regular NSAID use were substantially less likely to have adenomas (OR 0.4; 95% CI: 0.2-0.7) compared with occasional or nonusers. Similarly, compared with the lowest tertile, persons in the highest tertile of rectal mucosal apoptotic activity were much less likely to have adenomas (OR 0.12; 95% CI: 0.07-0.20). NSAID use and apoptotic activity were not correlated (r = 0.10). Mucosal proliferation was not related to adenomas or NSAID use.


CONCLUSIONS
Our observations suggest that NSAID use and higher levels of mucosal apoptosis are independently associated with a lower prevalence of adenomas. The study shows a strong field effect for apoptosis.
Martin
Christopher
C
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, 27599, USA.
Connelly
Alexandra
A
Keku
Temitope O
TO
Mountcastle
Sally B
SB
Galanko
Joseph
J
Woosley
John T
JT
Schliebe
Barbara
B
Lund
P Kay
PK
Sandler
Robert S
RS
D000236:Adenoma / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D035061:Control Groups; D019610:Cytoprotection; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D012007:Rectum / Q000473:pathology / Q000503:physiopathology; D012044:Regression Analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal