Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 141, Issue 12, Pages 2423-2429Publisher
WILEY
DOI: 10.1002/ijc.31007
Keywords
pancreatic cancer; prostaglandin E2 metabolite; biomarkers; cancer risk; body mass index
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Funding
- US National Cancer Institute at the National Institutes Health [R37CA070867, UM1CA173640, R01CA082729, UM1CA182910]
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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(2) 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.
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