Urinary prostaglandin E2 metabolite and gastric cancer risk in the Shanghai women's health study.
Chronic inflammation has been implicated in the etiology of gastric cancer. Prostaglandin E(2) (PGE(2)) is one of the major end-products of the cyclooxygenase-2 pathway, an enzyme that is an important mediator of inflammation. Using a novel method of quantifying the primary urinary metabolite of PGE(2) (PGE-M; 11alpha-hydroxy-9,15-dioxo-2,3,4,5-tetranorprostane-1,20-dioic acid), we evaluated urinary PGE-M concentrations in association with subsequent risk of development of gastric cancer in the Shanghai Women's Health Study, a large population-based prospective cohort, using a nested case-control study design. Controls were matched (1:1) to 153 gastric cancer cases by menopausal status; age, time, and date of sample collection; time interval since last meal; and availability of urine sample. Odds ratios (95% confidence intervals) were calculated using conditional logistic regression adjusted for potential confounders. Baseline urinary PGE-M levels were slightly higher among gastric cancer cases with a median of 6.4 ng/mg creatinine (interquartile range, 3.4-11.2) compared with 5.4 ng/mg creatinine among controls (interquartile range, 2.8-9.0), but this difference was not statistically significant (P = 0.34, Wilcoxon). With increasing quartiles of urinary PGE-M levels, the odds ratios (95% confidence intervals) for risk of gastric cancer increased in quartiles 2 to 4: 1.00 (0.48-2.08), 1.40 (0.67-2.91), and 1.98 (0.95-4.13), with a statistically significant test for trend (P = 0.04). The association persisted after additional adjustment for Helicobacter pylori status and was slightly strengthened among non-nonsteroidal anti-inflammatory drug users, subjects with positive H. pylori status, and for cases diagnosed within 46 months after study enrollment. Our findings suggest that higher levels of urinary PGE-M, a marker of inflammation, may be associated with gastric cancer risk.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. donglm@mail.nih.gov
Linda M
LM
Dong
Xiao-Ou
XO
Shu
Yu-Tang
YT
Gao
Ginger
G
Milne
Bu-Tian
BT
Ji
Gong
G
Yang
Hong-Lan
HL
Li
Nathaniel
N
Rothman
Wei
W
Zheng
Wong-Ho
WH
Chow
Christian C
CC
Abnet
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D002681:China; D015331:Cohort Studies; D005260:Female; D016481:Helicobacter Infections / Q000473:pathology / Q000601:surgery / Q000652:urine; D016480:Helicobacter pylori / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011453:Prostaglandins / Q000652:urine*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000473:pathology / Q000601:surgery / Q000652:urine*; D016387:Women's Health
D014408:Biomarkers, Tumor; D011453:Prostaglandins; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid