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Prospective Study of Urinary Prostaglandin E₂ Metabolite and Colorectal Cancer Risk

Qiuyin Cai, Yu-Tang Gao, Wong-Ho Chow, Xiao-Ou Shu, Gong Yang, Bu-Tian Ji, Wanqing Wen, Nathaniel Rothman, Hong-Lan Li, Jason D. Morrow, Wei Zheng

From the Department of Medicine, Center for Epidemiology Research, and Vanderbilt-Ingram Cancer Center; Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN; Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China; and the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD

Address reprint requests to Wei Zheng, MD, PhD, Vanderbilt Center for Epidemiology Research, Vanderbilt University School of Medicine, Medical Center North, S-1121, 1161 21st Ave South, Nashville, TN 37232-2587; e-mail: wei.zheng{at}vanderbilt.edu

Purpose: Overexpression of cyclooxygenase-2 (COX-2) has been shown to play a major role in colorectal cancer pathogenesis. However, no human study has directly investigated whether biomarkers of COX-2 overexpression may predict colorectal cancer risk. We evaluated the association of urinary prostaglandin E₂ metabolite (PGE-M) levels and colorectal cancer risk

Methods: A nested case-control study was conducted within the Shanghai Women's Health Study, in which 74,942 Chinese women ages 40 to 70 years were recruited from 1997 to 2000. Urinary PGE-M in 150 cohort members who developed colorectal cancer during the follow-up were compared with 150 matched controls.

Results: The baseline level of urinary PGE-M was more than 50% higher in cases than in controls. The relative risks (RRs) of developing colorectal cancer were elevated from 1.0 to 2.5 (95% CI, 1.1 to 5.8), 4.5 (95% CI, 1.9 to 10.9), and 5.6 (95% CI, 2.4 to 13.5) with increasing quartiles of urinary PGE-M levels (P for trend < .001). The positive association was observed for both colon cancer (RR = 4.9; 95% CI, 1.7 to 14.7 for the highest v lowest quartile; P for trend = .009) and rectal cancer (RR = 7.2; 95% CI, 1.7 to 30.7; P for trend = .048), and for colorectal cancer cases diagnosed in the first 30 months (RR = 7.6; 95% CI, 1.8 to 32.0; P for trend = .035) and subsequent months (RR = 4.4, 95% CI, 1.5 to 13.3; P for trend = .012) of follow-up.

Conclusion: Given its strong association with colorectal cancer risk, urinary PGE-M may be a promising biomarker for risk assessment of this common malignancy.

Supported by National Institutes of Health Grants No. CA70867, CA95103, GM15431, CA77839, DK48831, RR00095, and CA97386.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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