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RE: Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk

Abstract : Obesity is a risk factor for breast cancer in postmenopausal women. In their recent article, Gunter et al. found that associations between breast cancer risk and circulating levels of adipokines were null to modest. Importantly, they underscored that adipokines primarily function in a paracrine manner. Hence, adipokine plasma levels might be a poor surrogate for breast tissue levels (1). This is reminiscent of the situation observed with vitamin D. Obesity is inversely associated with vitamin D levels (2), and vitamin D inadequacy is observed in postmenopausal women (2). Moreover, 1,25-dihydroxyvitamin D (1,25D), the active metabolite of vitamin D, limits adipose tissue inflammation and suppresses leptin stimulation of cancer growth (3). As for adipokines, studies that have investigated the association between circulating levels of vitamin D and breast cancer risk gave mixed results (4,5). Could vitamin D and adipokines be two faces of the same coin? Vitamin D is barely active and requires two successive hydroxylations to produce 1,25D. The first hydroxylation is catalyzed in the liver by CYP2R1, the second one in the kidney by CYP27B1. This is the vitamin D endocrine system in which 1,25D is released in blood circulation and controls calcium homeostasis and skeletal health. Circulating 25(OH)-vitamin D levels between 50 and 75 nmol/L are considered indicative of vitamin D sufficiency. A paradigm shift recently occurred with the discovery of autocrine/paracrine vitamin D signaling in many tissues. In autocrine/paracrine systems, molecules are produced, act, and are degraded locally. Therefore, the autocrine/paracrine vitamin D signaling does not affect circulating levels of vitamin D metabolites. Two important features of the autocrine/paracrine vitamin D system are: 1) the regulation of CYP2R1 and CYP27B1 expression by inflammatory stimuli (6) and 2) the local storage of vitamin D in fat tissue (6). Hence, hydroxylated metabolites of vitamin D can be produced locally in response to inflammatory stimuli if sufficient local storage of vitamin D exists. Note that vitamin D
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Submitted on : Friday, April 15, 2016 - 1:18:25 PM
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Nelly Wion-Barbot, Didier Wion. RE: Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk. JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), 2016, 108 (1), pp.djv320. ⟨10.1093/jnci/djv320⟩. ⟨inserm-01302887⟩

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