Data from Urinary PGE-M Levels Are Associated with Risk of Colorectal Adenomas and Chemopreventive Response to Anti-Inflammatory Drugs

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. We conducted a prospective case–control study nested within the Nurses' 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 an LC/MS assay. Compared with women in the lowest quartile of urinary PGE-M, women in the highest quartile had a multivariate 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 <1 cm in greatest diameter with tubular/unspecified histology); and 1.66 (95% CI, 1.04–2.67) for high-risk adenoma (adenoma ≥1 cm 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).Urinary PGE-M is associated with an increased risk of high-risk adenoma. Anti-inflammatory drugs seem 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. Cancer Prev Res; 7(7); 758–65. ©2014 AACR.