title: Association between urinary prostaglandin E2 metabolite and breast cancer risk: a prospective, case-cohort study of postmenopausal women.
abstract: Overweight or obese women are at increased risk of developing and dying from breast cancer. Obesity-driven inflammation may stimulate prostaglandin E2 (PGE2)-mediated aromatase activation and estrogen biosynthesis in breast tissues. We hypothesized that increased production of PGE2 would contribute to elevated breast cancer risk in postmenopausal women. We carried out a case-cohort study with 307 incident breast cancer cases and 300 subcohort members from the Sister Study cohort. HRs and 95% confidence intervals (CI) were estimated for the association between urinary levels of a major PGE2 metabolite (PGE-M) and breast cancer risk using Prentice's pseudo-likelihood approach. Several lifestyle factors were associated with urinary levels of PGE-M: smoking, high-saturated fat diet, and obesity increased urinary PGE-M, and use of nonsteroidal antiinflammatory drugs (NSAID) decreased urinary PGE-M. Although there was no association between urinary PGE-M and postmenopausal breast cancer risk in the overall analysis or among regular users of NSAIDs, there was a positive association among postmenopausal women who did not regularly use NSAIDs with HRs of 2.1 [95% confidence interval (CI): 1.0-4.3]; 2.0 (95% CI: 1.0-3.9); and 2.2 (95% CI: 1.1-4.3) for the second, third, and highest quartiles of PGE-M. Our findings suggest a link between systemic PGE2 formation and postmenopausal breast cancer, and a possible modification of the association by lifestyle and pharmacologic interventions. If confirmed in larger studies, these results may have useful implications for the development of preventive strategies.
authors: Georgia Regents University Cancer Center, Medical College of Georgia, Section of Hematology/Oncology, Department of Medicine, 1410 Laney Walker Blvd., Augusta, GA 30912, USA. sankim@gru.edu
authors: Sangmi
authors: S
authors: Kim
authors: Jack A
authors: JA
authors: Taylor
authors: Ginger L
authors: GL
authors: Milne
authors: Dale P
authors: DP
authors: Sandler
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000652:urine*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D016022:Case-Control Studies; D015232:Dinoprostone / Q000652:urine; D005260:Female; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000188:drug therapy; D017698:Postmenopause / Q000187:drug effects*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; D015232:Dinoprostone
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