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.
Authors' Affiliations: University of Aberdeen, Aberdeen, United Kingdom; Departments of.
Navya
N
Bezawada
Nutrition, Epidemiology, Harvard School of Public Health;
Mingyang
M
Song
Nutrition.
Kana
K
Wu
Division of Gastroenterology, Massachusetts General Hospital;
Raaj S
RS
Mehta
Division of Clinical Pharmacology, Vanderbilt University, Tennessee.
Ginger L
GL
Milne
Epidemiology, Harvard School of Public Health; Department of Pathology; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; and.
Shuji
S
Ogino
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; and.
Charles S
CS
Fuchs
Nutrition, Epidemiology, Harvard School of Public Health; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital;
Edward L
EL
Giovannucci
Division of Gastroenterology, Massachusetts General Hospital; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital; achan@mgh.harvard.edu.
Andrew T
AT
Chan
D000236:Adenoma / Q000209:etiology / Q000517:prevention & control* / Q000652:urine*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000209:etiology / Q000517:prevention & control* / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011453:Prostaglandins / Q000652:urine*; D012307:Risk Factors
D000893:Anti-Inflammatory Agents; D014408:Biomarkers, Tumor; D011453:Prostaglandins; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid