Circulating isoflavone and lignan concentrations and prostate cancer risk: A meta-analysis of individual participant data from seven prospective studies including 2828 cases and 5593 controls.

Int J Cancer. 2018 Jul 4. doi: 10.1002/ijc.31640. [Epub ahead of print] Perez-Cornago A1, Appleby PN1, Boeing H2, Gil L3,4, Kyrø C5, Ricceri F6,7, Murphy N8, Trichopoulou A9, Tsilidis KK10,11, Khaw KT12, Luben RN12, Gislefoss RE13, Langseth H13, Drake I14, Sonestedt E14, Wallström P14,15, Stattin P16, Johansson A17, Landberg R18,19, Nilsson LM20, Ozasa K21, Tamakoshi A22, Mikami K23, Kubo T24, Sawada N25, Tsugane S25, Key TJ1, Allen NE26, Travis RC1. Author information 1 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. 2 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. 3 Public Health Division of Gipuzkoa-BIODONOSTIA, Basque Regional Health Department, Spain. 4 CIBER of Epidemiology and Public Health, Spain. 5 Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark. 6 Department of Clinical and Biological Sciences, University of Turin, Italy. 7 Unit of Epidemiology, Regional Health Service ASL TO3, Italy. 8 Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. 9 Hellenic Health Foundation, Alexandroupoleos 23, Athens, Greece. 10 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. 11 Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. 12 Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 13 Department of Research, Cancer Registry of Norway, Oslo, Norway. 14 Department of Clinical Sciences in Malmö, Lund University, Jan Waldenströms gata 35, 205 02, Malmö, Sweden. 15 Clinical Research Centre, Skåne University Hospital, 205 02, Malmö, Sweden. 16 Department of Surgical Sciences, Uppsala University, 751 87 Uppsala, Sweden. 17 Nutritional Research and Molecular Periodontology, Umeå University, Sweden. 18 Department of Biology and Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, 412 96 Gothenburg, Sweden. 19 Department of Public health and clinical medicine, Nutritional research, Umeå university, Umeå Sweden. 20 Department of Public health and clinical medicine, Nutritional research, Umeå university, & Arctic Research Centre at Umeå university, Umeå Sweden. 21 Department of Epidemiology, Radiation Effects Research Foundation, 5-2 Hijiyama-koen, Minami-ku, Hiroshima, 732-0815, Japan. 22 Department of Public Health, Hokkaido University Graduate School of Medicine, Kita 8, Nishi 5, Kita-ku, Sapporo, 060-0808, Japan. 23 Department of Urology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamikgyo-ku, Kyoto,602-8566, Japan. 24 Department of Preventive Medicine and Community Health, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-0804, Japan. 25 Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. 26 Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Big Data Institute, University of Oxford, Oxford OX3 7LF, United Kingdom. Abstract Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between pre-diagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs Q1=0.61, 95% confidence interval [CI]=0.39-0.97), although there was no significant trend (OR per 75 percentile increase=0.69, 95 CI=0.46-1.05, Ptrend =0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs Q1=0.70, 0.45-1.10, and 0.71, 0.45-1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that pre-diagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high. This article is protected by copyright. All rights reserved. KEYWORDS: isoflavones; lignans; phytoestrogens; pooled analysis; prostate cancer risk