COX-2 expression in adenoma: an imperfect marker for chemoprevention
- Massachusetts General Hospital, Gastrointestinal Unit, Boston, Massachusetts, USA
- Correspondence to Dr Andrew T Chan, Massachusetts General Hospital, Gastrointestinal Unit, 55 Fruit Street, GRJ-722, Boston, MA 02114, USA;
Four randomised, placebo-controlled studies have each shown that daily aspirin use reduces the occurrence of colorectal adenomatous polyps among individuals with a history of prior colorectal adenomas or cancer.1–4 In one of these trials, conducted by the Association pour la Prevention par l'Aspirine du Cancer Colorectal (APACC), 272 patients were randomised to two doses of a soluble aspirin salt (lysine acetylsalicylate) at 160 mg or 300 mg or placebo after removal of at least three adenomas or one adenoma at least 6 mm in diameter in a clearing colonoscopy. Compared with placebo, aspirin treatment at either dose was associated with a 37% reduction in risk of any recurrent adenoma and 70% reduction in risk of recurrent adenoma greater than 5 mm at the year 1 surveillance colonoscopy.3 In this issue of Gut, Benamouzig and colleagues (see page 622) now present a secondary analysis of a subset of 136 participants in the APACC trial.5 The authors examined immunohistochemical expression of cyclooxygenase-2 (COX-2) in the adenomas resected at the baseline clearing colonoscopy in relation to aspirin use and risk of adenoma recurrence at the year 1 or 4 surveillance colonoscopy. Aspirin is likely, at least in part, to prevent colorectal neoplasia through inhibition of COX-2, the rate-limiting step for the conversion of arachidonic acid to prostaglandins and related eicosanoids. COX-2 promotes inflammation and cell proliferation, and colorectal cancers often over-express this enzyme.6 Thus, the study by Benamouzig et al is a unique opportunity to examine whether the likelihood of overall adenoma recurrence as well as the effect of aspirin on recurrence varies according to tumorous expression of COX-2 in the baseline adenoma.
As a caveat, a formal presentation of the final main results of the APACC trial incorporating the outcomes at the year 4 colonoscopy has not yet been published except …