Urinary PGE-M levels are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs.

Objective: Prostaglandin E2 (PGE2) promotes colorectal carcinogenesis. Overall systemic PGE2 production can be assessed by measuring its major metabolite, PGE-M, in urine. We examined the potential role of PGE-M as a biomarker for colorectal adenoma risk and chemopreventive response to anti-inflammatory drugs. Methods: We conducted a prospective case-control study nested within the Nurses9 Health Study. Among women who previously provided a urine sample, we identified 420 cases diagnosed with colorectal adenoma during follow-up and matched them to 420 endoscopy-negative controls. We measured urinary PGE-M using a liquid chromatographic/mass spectrometric assay. Results: Compared with women in the lowest quartile of urinary PGE-M, women in the highest quartile had a multivariate odds ratio(OR) of 1.40(95% confidence interval(CI), 0.92-2.14) for any adenoma; 0.91(95% CI,0.48-1.72) for low-risk adenoma (solitary adenoma <1cm in greatest diameter with tubular/unspecified histology); and 1.66 (95%CI,1.04-2.67) for high-risk adenoma (adenoma ≥1cm in greatest diameter and/or tubulovillous, villous or high grade dysplasia histology or multiple adenomas of any size or histology). Regular use of anti-inflammatory drugs (≥2 standard tablets of aspirin/NSAIDs per week) was associated with a significant reduction in adenoma risk (multivariate OR, 0.61;95% CI, 0.43-0.87) in women with high baseline PGE-M (quartiles 2-4), but not low PGE-M (quartile 1). Conclusions: Urinary PGE-M is associated with an increased risk of high-risk adenoma. Anti-inflammatory drugs appear to reduce adenoma risk among women with high, but not low PGE-M. Urinary PGE-M may serve as a biomarker to define subsets of the population who may obtain differential chemopreventive benefit from anti-inflammatory drugs. -