{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:46:48Z","timestamp":1789472808094,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,30]],"date-time":"2024-06-30T00:00:00Z","timestamp":1719705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"the Italian Ministry of Health with Ricerca Finalizzata","doi-asserted-by":"publisher","award":["GR-2013-02358807"],"award-info":[{"award-number":["GR-2013-02358807"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ricerca Corrente, and 5 \u00d7 1000 funds","award":["GR-2013-02358807"],"award-info":[{"award-number":["GR-2013-02358807"]}]},{"name":"the IBIS-II study from Cancer Research UK","award":["GR-2013-02358807"],"award-info":[{"award-number":["GR-2013-02358807"]}]},{"name":"the Breast Cancer Research Foundation, and AstraZeneca","award":["GR-2013-02358807"],"award-info":[{"award-number":["GR-2013-02358807"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Obesity is a risk factor for postmenopausal breast cancer (BC), and evidence suggests a role for adiponectin in the relationship between obesity and BC. We investigated whether adiponectin or other biomarkers mediate the effect of body mass index (BMI) on postmenopausal BC risk in a cohort study nested in the IBIS-II Prevention Trial. We measured adiponectin, leptin, IGF-I, IGFBP-1, high-sensitivity C-reactive protein, glycemia, insulin, HOMA-IR index, and SHBG in baseline and 12-month serum samples from 123 cases and 302 matched controls in the placebo arm of the IBIS-II Prevention trial. We conducted the main mediation analysis considering baseline BMI as an exposure and the 12-month adiponectin increase as a mediator after adjustment for the Tyrer\u2013Cuzick score and the lipid-lowering medications\/supplements use. In the multivariable Cox model, both the 12-month adiponectin increase (HR, 0.60; 95%CI, 0.36\u20131.00) and BMI were associated with BC risk (HR, 1.05; 95%CI, 1.00\u20131.09), with a 40% reduction in women with a 12-month increase in adiponectin. A significantly higher cumulative hazard of BC events was observed in obese women (BMI &gt; 30) with decreased adiponectin (p = 0.0087). No mediating effect of the adiponectin increase on the total effect of BMI on BC risk was observed (natural indirect effect: HR, 1.00; 95%CI, 0.98\u20131.02). Raising adiponectin levels might be an attractive target for postmenopausal BC prevention.<\/jats:p>","DOI":"10.3390\/nu16132098","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T04:53:27Z","timestamp":1719809607000},"page":"2098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Mediation Analysis of Obesity and Adiponectin Association with Postmenopausal Breast Cancer Risk: A Nested Cohort Study in the International Breast Cancer Intervention Study II (IBIS-II) Prevention Trial"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-2933","authenticated-orcid":false,"given":"Debora","family":"Macis","sequence":"first","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5956-4340","authenticated-orcid":false,"given":"Federica","family":"Bellerba","sequence":"additional","affiliation":[{"name":"Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4939-6240","authenticated-orcid":false,"given":"Valentina","family":"Aristarco","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4131-2030","authenticated-orcid":false,"given":"Harriet","family":"Johansson","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-1688","authenticated-orcid":false,"given":"Aliana","family":"Guerrieri-Gonzaga","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2162-4002","authenticated-orcid":false,"given":"Matteo","family":"Lazzeroni","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Sestak","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Population Health, Queen Mary University of London, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Cuzick","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Population Health, Queen Mary University of London, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2635-4491","authenticated-orcid":false,"given":"Andrea","family":"DeCensi","sequence":"additional","affiliation":[{"name":"Wolfson Institute of Population Health, Queen Mary University of London, London EC1M 6BQ, UK"},{"name":"Division of Medical Oncology, Ente Ospedaliero Galliera, 16128 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-2128","authenticated-orcid":false,"given":"Bernardo","family":"Bonanni","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-4548","authenticated-orcid":false,"given":"Sara","family":"Gandini","sequence":"additional","affiliation":[{"name":"Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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