Association between urinary prostaglandin E2 metabolite and breast cancer risk: a prospective, case-cohort study of postmenopausal women
Menée auprès de 307 patientes ménopausées atteintes d'un cancer du sein et auprès de 300 femmes saines ayant une sœur atteinte de la maladie, cette étude prospective américaine évalue l'association entre le niveau urinaire d'un métabolite de la prostaglandine E2 et le risque de cancer du sein
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. Hazard ratios (HRs) and 95% confidence intervals (CIs) 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 anti-inflammatory drugs (NSAIDs) 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% 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 pharmacological interventions. If confirmed in larger studies, these results may have useful implications for the development of preventive strategies.
Cancer Prevention Research , résumé, 2013