Aspirin and the risk of colorectal cancer in relation to the expression of COX-2.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Chan
Andrew T
AT
Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA. achan@partners.org
Ogino
Shuji
S
Fuchs
Charles S
CS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000517:prevention & control; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012306:Risk
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D051546:Cyclooxygenase 2; D001241:Aspirin