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      Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta‐analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls

      research-article
      1 , , 1 , 2 , 3 , 4 ,   5 , 6 , 7 ,   8 , 9 , 10 , 11 , 12 , 12 , 13 , 13 , 14 , 14 , 14 , 15 , 16 , 17 , 18 , 19 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 25 , 1 , 26 , 27 , 1
      International Journal of Cancer
      John Wiley & Sons, Inc.
      prostate cancer risk, phytoestrogens, isoflavones, lignans, pooled analysis

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          Abstract

          Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic 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, p trend = 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 prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.

          Abstract

          What's new?

          The role of phytoestrogens in prostate cancer development is uncertain. Here, the authors analysed participant data from seven prospective studies on the association between pre‐diagnostic circulating concentrations of isoflavones (mainly found in soybeans) and lignans (mainly found in cereal, nuts, and vegetables) and prostate cancer risk. They found no strong associations but point to the fact that further data are needed to examine associations based on disease aggressiveness, especially in populations with high isoflavone intakes.

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          Most cited references34

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          Interaction between phenolics and gut microbiota: role in human health.

          Dietary phenolic compounds are often transformed before absorption. This transformation modulates their biological activity. Different studies have been carried out to understand gut microbiota transformations of particular polyphenol types and identify the responsible microorganisms. Although there are potentially thousands of different phenolic compounds in the diet, they are typically transformed to a much smaller number of metabolites. The aim of this review was to discuss the current information about the microbial degradation metabolites obtained from different phenolics and their formation pathways, identifying their differences and similarities. The modulation of gut microbial population by phenolics was also reviewed in order to understand the two-way phenolic-microbiota interaction. Clostridium and Eubacterium genera, which are phylogenetically associated, are other common elements involved in the metabolism of many phenolics. The health benefits from phenolic consumption should be attributed to their bioactive metabolites and also to the modulation of the intestinal bacterial population.
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            Equol: history, chemistry, and formation.

            Equol, first isolated from equine urine in 1932 and identified 50 years later in human urine as a metabolite of the soy isoflavones, daidzin and daidzein, is produced by intestinal bacteria in some, but not all, adults. This observation led to the term equol-producers to define those adults that could make equol in response to consuming soy isoflavones and the hypothesis that the health benefits of soy-based diets may be greater in equol-producers than in equol nonproducers. By virtue of a chiral center, equol occurs as a diastereoisomer and intestinal bacteria are enantiospecific in synthesizing exclusively the S-(-)equol enantiomer, an enantiomer that has selective affinity for the estrogen receptor-beta. Both enantiomers are of interest from a clinical and pharmacological perspective and are currently being developed as nutraceutical and pharmacological agents. The wide range of biological activities these enantiomers possess warrants their investigation for the treatment of a number of hormone-related conditions involving estrogen-dependent and androgen-related conditions. The following review describes the history, chemistry, and factors governing the intestinal bacterial formation of equol.
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              Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies.

              Sex hormones in serum have been hypothesized to influence the risk of prostate cancer. We performed a collaborative analysis of the existing worldwide epidemiologic data to examine these associations in a uniform manner and to provide more precise estimates of risks. Data on serum concentrations of sex hormones from 18 prospective studies that included 3886 men with incident prostate cancer and 6438 control subjects were pooled by the Endogenous Hormones and Prostate Cancer Collaborative Group. Relative risks (RRs) of prostate cancer by fifths of serum hormone concentration were estimated by use of conditional logistic regression with stratification by study, age at recruitment, and year of recruitment. All statistical tests were two-sided. No associations were found between the risk of prostate cancer and serum concentrations of testosterone, calculated free testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, androstanediol glucuronide, estradiol, or calculated free estradiol. The serum concentration of sex hormone-binding globulin was modestly inversely associated with prostate cancer risk (RR in the highest vs lowest fifth = 0.86, 95% confidence interval = 0.75 to 0.98; P(trend) = .01). There was no statistical evidence of heterogeneity among studies, and adjustment for potential confounders made little difference to the risk estimates. In this collaborative analysis of the worldwide data on endogenous hormones and prostate cancer risk, serum concentrations of sex hormones were not associated with the risk of prostate cancer.
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                Author and article information

                Contributors
                aurora.perez-cornago@ndph.ox.ac.uk
                Journal
                Int J Cancer
                Int. J. Cancer
                10.1002/(ISSN)1097-0215
                IJC
                International Journal of Cancer
                John Wiley & Sons, Inc. (Hoboken, USA )
                0020-7136
                1097-0215
                29 September 2018
                01 December 2018
                : 143
                : 11 ( doiID: 10.1002/ijc.v143.11 )
                : 2677-2686
                Affiliations
                [ 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 San Sebastian Spain
                [ 4 ] CIBER of Epidemiology and Public Health Madrid Spain
                [ 5 ] Danish Cancer Society Research Center, Strandboulevarden 49 Copenhagen Denmark
                [ 6 ] Department of Clinical and Biological Sciences University of Turin Turin Italy
                [ 7 ] Unit of Epidemiology Regional Health Service ASL TO3 Grugliasco Italy
                [ 8 ] Section of Nutrition and Metabolism International Agency for Research on Cancer Lyon France
                [ 9 ] Hellenic Health Foundation 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 Malmö Sweden
                [ 15 ] Clinical Research Centre Skåne University Hospital Malmö Sweden
                [ 16 ] Department of Surgical Sciences Uppsala University Uppsala Sweden
                [ 17 ] Nutritional Research and Molecular Periodontology Umeå University Umeö Sweden
                [ 18 ] Department of Biology and Biological Engineering Food and Nutrition Science, Chalmers University of Technology Gothenburg Sweden
                [ 19 ] Department of Public Health and Clinical Medicine Nutritional Research, Umeå University Umeå Sweden
                [ 20 ] Arctic Research Centre, Umeå University Umeå Sweden
                [ 21 ] Department of Epidemiology Radiation Effects Research Foundation Minami‐ku Hiroshima Japan
                [ 22 ] Department of Public Health Hokkaido University Graduate School of Medicine Kita‐ku Sapporo Japan
                [ 23 ] Department of Urology Kyoto Prefectural University of Medicine Graduate School of Medical Science Kamikgyo‐ku Kyoto Japan
                [ 24 ] Department of Preventive Medicine and Community Health University of Occupational and Environmental Health Yahatanishi‐ku Kitakyushu Japan
                [ 25 ] Epidemiology and Prevention Group Center for Public Health Sciences, National Cancer Center Tokyo Japan
                [ 26 ] Clinical Trial Service Unit, Nuffield Department of Population Health Big Data Institute, University of Oxford Oxford United Kingdom
                [ 27 ] Epidemiological Studies Unit, Nuffield Department of Population Health Big Data Institute, University of Oxford Oxford United Kingdom
                Author notes
                [*] [* ] Correspondence to: Aurora Perez‐Cornago, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom, Tel.: +44‐1865‐289600, Fax: +44‐1865‐289610, E‐mail: aurora.perez-cornago@ 123456ndph.ox.ac.uk
                Author information
                https://orcid.org/0000-0002-5652-356X
                https://orcid.org/0000-0002-9083-8960
                https://orcid.org/0000-0001-8749-9737
                https://orcid.org/0000-0003-3347-8249
                https://orcid.org/0000-0002-6500-6310
                Article
                IJC31640
                10.1002/ijc.31640
                6283047
                29971774
                5803afae-2861-44ad-921f-cec93fd3c41e
                © 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 March 2018
                : 03 May 2018
                : 07 May 2018
                Page count
                Figures: 3, Tables: 3, Pages: 10, Words: 9141
                Funding
                Funded by: European Union
                Award ID: QRLT 2000–00266
                Funded by: Swedish Cancer foundation
                Funded by: Swedish Council for Working Life and Social Research, Swedish Cancer Society, the Albert Påhlsson Foundation for Scientific Research, the Gunnar Nilsson Cancer Foundation, Skåne University Hospital – Foundations and Donations, the Malmö General Hospital Foundation for the Combating of Cancer and the Ernhold Lundström Foundation for Scientific Research
                Funded by: Ministry of Education, Culture, Sports, Science and Technology
                Funded by: Ministry of Health, Labour and Welfare of Japan
                Funded by: Research on Risk of Chemical Substances
                Award ID: 17015049
                Award ID: H17‐kagakuippan‐014
                Funded by: Comprehensive 10‐Year Strategy for Cancer Control
                Award ID: H18‐sanjigan‐ippan‐001
                Funded by: Grants‐in‐Aid for Cancer Research
                Award ID: 19shi‐2
                Funded by: Grants‐in‐Aid for Scientific Research
                Award ID: 11181101
                Award ID: 6279102
                Award ID: 5151069
                Award ID: 4151063
                Award ID: 3151064
                Award ID: 2151065
                Award ID: 1010068
                Award ID: 63010074
                Award ID: 62010074
                Award ID: 61010076
                Funded by: Grant‐in‐Aid for Scientific Research on Priority Areas (2) from the Ministry of Education, Culture, Sports, Science and Technology of Japan
                Award ID: 14031221
                Funded by: The Nordic Cancer Union; Phytoprevent Project of the European Commission; Sigrid Juselius Foundation, Helsinki, Finland
                Funded by: Janus NBSBWG: The Norwegian Institute of Public Health
                Funded by: Medical Research Council and Cancer Research UK
                Funded by: EPIC‐Denmark: Danish Cancer Society
                Funded by: MORGEN‐EPIC cohort of the EPIC Bilthoven centre: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR) and Statistics Netherlands (the Netherlands).
                Funded by: EPIC‐Greece: the Hellenic Health Foundation. EPIC‐Italy: Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy.
                Funded by: Cancer Research UK
                Award ID: C570/A11691
                Award ID: C8221/A19170
                Categories
                Cancer Epidemiology
                Cancer Epidemiology
                Custom metadata
                2.0
                ijc31640
                1 December 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.3 mode:remove_FC converted:06.12.2018

                Oncology & Radiotherapy
                prostate cancer risk,phytoestrogens,isoflavones,lignans,pooled analysis
                Oncology & Radiotherapy
                prostate cancer risk, phytoestrogens, isoflavones, lignans, pooled analysis

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