Background Regular use of aspirin reduces the risk of a colorectalneoplasm, but the mechanism by which aspirin affects carcinogenesisin the colon is not well understood.
Methods We estimated cyclooxygenase-2 (COX-2) expression byimmunohistochemical assay of sections from paraffin-embeddedcolorectal-cancer specimens from two large cohorts of participantswho provided data on aspirin use from a questionnaire every2 years. We applied Cox regression to a competing-risks analysisto compare the effects of aspirin use on the relative risk ofcolorectal cancer in relation to the expression of COX-2 inthe tumor.
Results During 2,446,431 person-years of follow-up of 82,911women and 47,363 men, we found 636 incident colorectal cancersthat 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 relationto COX-2 expression (P for heterogeneity=0.02). Regular aspirinuse conferred a significant reduction in the risk of colorectalcancers that overexpressed COX-2 (multivariate relative risk,0.64; 95% confidence interval [CI], 0.52 to 0.78), whereas regularaspirin use had no influence on tumors with weak or absent expressionof COX-2 (multivariate relative risk, 0.96; 95% CI, 0.73 to1.26). The age-standardized incidence rate for cancers thatoverexpressed COX-2 was 37 per 100,000 person-years among regularaspirin users, as compared with 56 per 100,000 person-yearsamong those who did not use aspirin regularly; in contrast,the rate for cancers with weak or absent COX-2 expression was27 per 100,000 person-years among regular aspirin users, ascompared with 28 per 100,000 person-years among nonregular aspirinusers.
Conclusions Regular use of aspirin appears to reduce the riskof colorectal cancers that overexpress COX-2 but not the riskof colorectal cancers with weak or absent expression of COX-2.
Source Information
From the Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School (A.T.C.); the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School (S.O.); the Department of Medical Oncology, Dana–Farber Cancer Institute (S.O., C.S.F.); and the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (A.T.C., C.S.F.) — all in Boston.
Address reprint requests to Dr. Chan at the Gastrointestinal Unit, Massachusetts General Hospital, 55 Fruit St., GRJ 728A, Boston, MA 02114, or at achan{at}partners.org.
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