A molecular/epidemiologic analysis of expression of cyclooxygenases 1 and 2, use of nonsteroidal antiinflammatory drugs, and risk of colorectal adenoma.
Nonsteroidal antiinflammatory drugs (NSAIDs) are postulated to protect against colorectal cancer and adenomas at least in part by a cyclooxygenase (COX-mediated mechanism. The results reported herein address the questions of what factors are associated with expression (relative messenger RNA levels) of COX-1 and COX-2 in colorectal adenomas and whether there is heterogeneity in the protective effect of NSAIDs by levels of COX expression. Paraffin-embedded tissue samples and data describing selected risk factors were obtained from cases enrolled in a case-control study of colorectal adenomatous polyps. RNA was isolated from paraffin-embedded specimens. Samples of complementary DNA were quantified using a fluorescence-based real-time detection method. We tested for differences in levels of COX expression among selected subgroups of cases using a standard Student t test. Odds ratios for the effects of NSAID variables were calculated using unconditional logistic regression in order to make use of all available data on COX expression. Results suggest that use of NSAIDs is associated with lower levels of COX-2 expression and that the protective effect of NSAIDs on polyp occurrence is stronger in the subgroup of cases with higher expression of COX-2 and a higher COX-2/COX-1 ratio. The results suggest that at least part of the protective effect of NSAIDs on the risk of colorectal adenoma involves a COX-mediated pathway.
Haile
Robert W
RW
USC/Norris Cancer Center, Keck School of Medicine, Department of Preventive Medicine, University of Southern California, 1441 Eastlake Ave, Suite 4455, Los Angeles, CA 90033, USA. haile@usc.edu
Yochim
Ji Min
JM
Cortessis
Victoria K
VK
Lin
Jesse
J
Levine
A Joan
AJ
Diep
Anh
A
Danenberg
Kathy
K
Danenberg
Peter
P
D000236:Adenoma / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016022:Case-Control Studies; D003111:Colonic Polyps / Q000453:epidemiology / Q000235:genetics; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015994:Incidence; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D016017:Odds Ratio; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012307:Risk Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008565:Membrane Proteins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases