{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T04:09:51Z","timestamp":1776485391634,"version":"3.51.2"},"reference-count":29,"publisher":"Georg Thieme Verlag KG","issue":"04","funder":[{"name":"HYPERCAN Study","award":["AIRC \u201c5xMILLE\u201d no. 12237"],"award-info":[{"award-number":["AIRC \u201c5xMILLE\u201d no. 12237"]}]},{"name":"POR FESR","award":["459 del 27\/11\/2018"],"award-info":[{"award-number":["459 del 27\/11\/2018"]}]},{"DOI":"10.13039\/100008648","name":"Pfizer Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008648","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Italian Ministry of University and Research","award":["1588"],"award-info":[{"award-number":["1588"]}]},{"name":"Instrumentation Laboratory"},{"name":"Italian Ministry of Health","award":["RF-2018-12367074"],"award-info":[{"award-number":["RF-2018-12367074"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background\u2003Elevated levels of key enzymes of the fibrinolytic system, such as tissue plasminogen activator (tPA), are reported as predictors of poor outcome in cancer patients. Limited information is available about their potential predictive value for breast cancer (BC) risk in the general population.<\/jats:p><jats:p>Aim\u2003We examined the association of tPA levels with BC risk in a case\u2013cohort study including women from the prospective Moli-sani cohort.<\/jats:p><jats:p>Methods\u2003A sample of 710 women (mean age: 54.6\u2009\u00b1\u200912.1 years) was selected as a subcohort and compared with 84 BC cases, in a median follow-up of 4.2 years. Incident cases of BC were validated through medical records. tPA plasma levels were measured using an enzyme-linked immunosorbent assay kit. Hazard ratio (HR) and 95% confidence interval (CI), adjusted for relevant covariates, were estimated by a Cox regression model using the Prentice method.<\/jats:p><jats:p>Results\u2003Compared with the lowest quartile (&lt;4.9\u2009ng\/mL), women in the highest quartile of tPA (&gt;11.2\u2009ng\/mL) had increased risk of BC (HRIVvsI: 2.20, 95% CI: 1.13\u20134.28) after adjusted for age, smoking, education, menopause, and residence. Further adjustment for biochemical markers did not modify this association. The risk of BC increased by 34% for each increase in 1 standard deviation of log-transformed tPA levels (p\u2009=\u20090.046). Elevated levels of tPA were associated mainly with estrogen-receptor-positive BC (2.08, 95% CI: 1.18\u20133.66).<\/jats:p><jats:p>Conclusion\u2003Higher levels of tPA, reported to predict cardiovascular risk, are a potential biomarker for BC risk, supporting the hypothesis of a \u201ccommon soil\u201d linking the pathogenic mechanisms of hormone-dependent tumors and cardiovascular disease.<\/jats:p>","DOI":"10.1055\/s-0040-1718531","type":"journal-article","created":{"date-parts":[[2020,10,18]],"date-time":"2020-10-18T22:35:01Z","timestamp":1603060501000},"page":"449-456","source":"Crossref","is-referenced-by-count":10,"title":["Tissue Plasminogen Activator Levels and Risk of Breast Cancer in a Case\u2013Cohort Study on Italian Women: Results from the Moli-sani Study"],"prefix":"10.1055","volume":"121","author":[{"given":"Simona","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Parisi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia","family":"De Curtis","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Gamba","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariarosaria","family":"Persichillo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Panzera","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Cerletti","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"de Gaetano","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Falanga","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy"},{"name":"School of Medicine, University of Milan Bicocca, Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Benedetta","family":"Donati","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Licia","family":"Iacoviello","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy"},{"name":"Department of Medicine and Surgery, Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the Moli-sani Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,10,18]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"R L Siegel","year":"2019","journal-title":"CA Cancer J Clin"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.02.010","article-title":"Epidemiology of breast cancer, a paradigm of the \u201ccommon soil\u201d hypothesis","author":"L Iacoviello","year":"2020","journal-title":"Semin Cancer Biol"},{"issue":"S 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