Prospective study of urinary prostaglandin E2 metabolite and pancreatic cancer risk.

Cui Y, Shu XO, Li HL, Yang G, Wen W, Gao YT, Cai Q, Rothman N, Yin HY, Lan Q, Xiang YB, Zheng W
Int J Cancer. 2017 141 (12): 2423-2429

PMID: 28815606 · PMCID: PMC5749224 · DOI:10.1002/ijc.31007

The cyclooxygenase 2 (COX-2) pathway is upregulated in many pancreatic cancer cells, and it is believed that carcinogenetic effects of COX-2 upregulation are largely through prostaglandin E2 (PGE2) overproduction. We tested this hypothesis by evaluating the association between urinary PGE2 metabolites (PGE-M), a biomarker of in vivo PGE2 overproduction, and pancreatic cancer risk. We conducted a case-control study with 722 subjects (239 cases and 483 controls) nested within two prospective cohort studies, the Shanghai Women's Health Study (SWHS) and Shanghai Men's Health Study (SMHS). Pre-diagnosis urine samples were measured for PGE-M using a liquid chromatography/tandem mass spectrometric method. Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (95%CI), with adjustment for potential confounders. Compared to those with the lowest urine level of PGE-M (the first quartile), individuals with higher urine levels of PGE-M had an increased risk of developing pancreatic cancer, with adjusted ORs (95%CI) of 1.63 (0.98-2.73), 1.55 (0.90-2.69) and 1.94 (1.07-3.51), for the second to the fourth quartile groups, respectively (p for trend = 0.054). This dose-response positive association was more evident among those who had BMI <25 kg/m than overweight individuals (p for interaction = 0.058). After excluding cases diagnosed in the first year of follow-up and their matched controls, this positive association persisted (p for trend = 0.037) and the interaction became statistically significant (p for interaction = 0.017). Our study adds additional evidence that the COX-2 pathway is involved in pancreatic carcinogenesis and suggests that urinary PGE-M may serve as a biomarker for predicting pancreatic cancer risk.

© 2017 UICC.

MeSH Terms (17)

Adult Aged Body Mass Index Case-Control Studies China Chromatography, Liquid Cyclooxygenase 2 Female Humans Logistic Models Male Middle Aged Odds Ratio Pancreatic Neoplasms Prospective Studies Prostaglandins Tandem Mass Spectrometry

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