Aspirin and the Risk of Colorectal Cancer in Relation to the Expression of COX-2
- 24 May 2007
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 356 (21), 2131-2142
- https://doi.org/10.1056/nejmoa067208
Abstract
Regular use of aspirin reduces the risk of a colorectal neoplasm, but the mechanism by which aspirin affects carcinogenesis in the colon is not well understood. We estimated cyclooxygenase-2 (COX-2) expression by immunohistochemical assay of sections from paraffin-embedded colorectal-cancer specimens from two large cohorts of participants who provided data on aspirin use from a questionnaire every 2 years. We applied Cox regression to a competing-risks analysis to compare the effects of aspirin use on the relative risk of colorectal cancer in relation to the expression of COX-2 in the tumor. During 2,446,431 person-years of follow-up of 82,911 women and 47,363 men, we found 636 incident colorectal cancers that were accessible for determination of COX-2 expression. Of the tumors, 423 (67%) had moderate or strong COX-2 expression. The effect of aspirin use differed significantly in relation to COX-2 expression (P for heterogeneity=0.02). Regular aspirin use conferred a significant reduction in the risk of colorectal cancers that overexpressed COX-2 (multivariate relative risk, 0.64; 95% confidence interval [CI], 0.52 to 0.78), whereas regular aspirin use had no influence on tumors with weak or absent expression of COX-2 (multivariate relative risk, 0.96; 95% CI, 0.73 to 1.26). The age-standardized incidence rate for cancers that overexpressed COX-2 was 37 per 100,000 person-years among regular aspirin users, as compared with 56 per 100,000 person-years among those who did not use aspirin regularly; in contrast, the rate for cancers with weak or absent COX-2 expression was 27 per 100,000 person-years among regular aspirin users, as compared with 28 per 100,000 person-years among nonregular aspirin users. Regular use of aspirin appears to reduce the risk of colorectal cancers that overexpress COX-2 but not the risk of colorectal cancers with weak or absent expression of COX-2.Keywords
This publication has 37 references indexed in Scilit:
- Low-Dose Aspirin for the Prevention of AtherothrombosisThe New England Journal of Medicine, 2005
- COX-2: A Molecular Target for Colorectal Cancer PreventionJournal of Clinical Oncology, 2005
- Cyclooxygenase-2 ExpressionClinical Cancer Research, 2004
- Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trialGastroenterology, 2003
- A Randomized Trial of Aspirin to Prevent Colorectal AdenomasThe New England Journal of Medicine, 2003
- A Randomized Trial of Aspirin to Prevent Colorectal Adenomas in Patients with Previous Colorectal CancerThe New England Journal of Medicine, 2003
- Aspirin, non-steroidal anti-inflammatory drugs and colorectal neoplasia: future challenges in chemopreventionCancer Causes & Control, 2003
- Overexpression of cyclooxygenase-2 correlates with advanced stages of colorectal cancerThe American Journal of Gastroenterology, 2002
- The Effect of Celecoxib, a Cyclooxygenase-2 Inhibitor, in Familial Adenomatous PolyposisThe New England Journal of Medicine, 2000
- Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomasGastroenterology, 1994