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Caffeine as a bioactive compound of coffee has not yet been studied in deep <jats:italic>in vitro<\/jats:italic>. Our study aimed at evaluating in a population cohort the effect of Italian\u2010style coffee consumption on prostate cancer risk and at investigating <jats:italic>in vitro<\/jats:italic> the potential antiproliferative and antimetastatic activity of caffeine on prostate cancer cell lines. 6,989 men of the Moli\u2010sani cohort aged \u226550 years were followed for a mean of 4.24\u2009\u00b1\u20091.35 years and 100 new prostate cancer cases were identified. The European Prospective Investigation into Cancer and Nutrition\u2010Food Frequency Questionnaire was used for the dietary assessment and the evaluation of Italian\u2010style coffee consumption. Two human prostate cancer cell lines, PC\u20103 and DU145, were tested with increasing concentrations of caffeine, and their proliferative\/metastatic features were evaluated. The newly diagnosed prostate cancer participants presented lower coffee consumption (60.1\u2009\u00b1\u200951.3 g\/day) compared to the disease\u2010free population (74.0\u2009\u00b1\u200951.7 g\/day) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Multiadjusted analysis showed that the subjects at highest consumption (&gt;3 cups\/day) had 53% lower prostate cancer risk as compared to participants at the lowest consumption (0\u20132 cups\/day) (<jats:italic>p<\/jats:italic>\u2009=\u20090.02). Both human prostate cancer cell lines treated with caffeine showed a significant reduction in their proliferative and metastatic behaviors (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In conclusion, reduction by Italian\u2010style coffee consumption of prostate cancer risk (&gt;3 cups\/day) was observed in epidemiological level. Caffeine appeared to exert both antiproliferative and antimetastatic activity on two prostate cancer cell lines, thus providing a cellular confirmation for the cohort study results.<\/jats:p>","DOI":"10.1002\/ijc.30720","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T05:03:56Z","timestamp":1493010236000},"page":"72-82","source":"Crossref","is-referenced-by-count":35,"title":["Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli\u2010sani cohort and cellular models"],"prefix":"10.1002","volume":"141","author":[{"given":"George","family":"Pounis","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Prevention IRCCS Istituto Neurologico Mediterraneo \u2013 NEUROMED Pozzilli (IS) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Tabolacci","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0, ISS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention IRCCS Istituto Neurologico Mediterraneo \u2013 NEUROMED Pozzilli (IS) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Cordella","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0, ISS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marialaura","family":"Bonaccio","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention IRCCS Istituto Neurologico Mediterraneo \u2013 NEUROMED Pozzilli (IS) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Rago","sequence":"additional","affiliation":[{"name":"Epicomed Research Srl. 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