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      Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe

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          Abstract

          Background:

          We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence.

          Methods:

          This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models.

          Results:

          After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02–1.21) for BMI, 1.13 (95% CI 1.04–1.23) for WC, 1.09 (95% CI 0.98–1.21) for HC, and 1.15 (95% CI 1.00–1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer ( P interaction<0.001), where never HT users showed an ∼20% increased risk per s.d. of BMI, WC, and HC compared to ever users.

          Conclusions:

          BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modification by HT use.

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          Most cited references22

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          Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

          In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Adiposity and cancer risk: new mechanistic insights from epidemiology.

            Excess body adiposity, commonly expressed as body mass index (BMI), is a risk factor for many common adult cancers. Over the past decade, epidemiological data have shown that adiposity-cancer risk associations are specific for gender, site, geographical population, histological subtype and molecular phenotype. The biological mechanisms underpinning these associations are incompletely understood but need to take account of the specificities observed in epidemiology to better inform future prevention strategies.
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              The role of adiponectin in cancer: a review of current evidence.

              Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies.
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                Author and article information

                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                23 May 2017
                25 April 2017
                : 116
                : 11
                : 1486-1497
                Affiliations
                [1 ]Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO) , 150 Cours Albert Thomas, 69008 Lyon, France
                [2 ]Section of Cancer Surveillance, International Agency for Research on Cancer (IARC-WHO) , 150 Cours Albert Thomas, 69008 Lyon, France
                [3 ]UKCRC Centre of Excellence for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast , University Road, Belfast BT7 1NN, UK
                [4 ]Network Aging Research (NAR), Heidelberg University , Bergheimer Straße 20, 69115 Heidelberg, Germany
                [5 ]Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ) , Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
                [6 ]Nuffield Department of Primary Care Health Sciences, University of Oxford , Woodstock Rd, Oxford OX2 6GG, UK
                [7 ]Hellenic Health Foundation , 13 Kaisareias & Alexandroupoleos, Athens 115 27, Greece
                [8 ]WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens , Mikras Asias 75, Athens 115 27, Greece
                [9 ]Department Agrotechnology and Food Sciences, Division of Human Nutrition, Wageningen University , PO Box 17, 6700AA Wageningen, The Netherlands
                [10 ]Department of Epidemiology and Preventive Medicine, University of Regensburg , Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
                [11 ]Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus , 45110 Ioannina, Greece
                [12 ]Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, South Kensington Campus , London SW7 2AZ, UK
                [13 ]Danish Cancer Society Research Center , Strandboulevarden 49, DK 2100 Copenhagen Ø Denmark
                [14 ]Icahn School of Medicine at Mount Sinai , 1 Gustave L. Levy Place, New York, NY 10029-5674, USA
                [15 ]Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM) , PO Box 1, 3720 BA Bilthoven, The Netherlands
                [16 ]Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya , 50603 Kuala Lumpur, Malaysia
                [17 ]Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca , Ronda de Levante, 11, 30008, Murcia, Spain
                [18 ]CIBER Epidemiología y Salud Pública (CIBERESP) , Melchor Fernández Almagro, 3-5, Madrid 28029, Spain
                [19 ]Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) , Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
                [20 ]German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) , Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
                [21 ]Department of Community Medicine, UiT The Arctic University of Norway , 9037 Tromsø, Norway
                Author notes
                Article
                bjc2017106
                10.1038/bjc.2017.106
                5520086
                28441380
                c6d279f3-2708-4be7-b43d-39f1633f84db
                Copyright © 2017 Cancer Research UK

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                : 12 November 2016
                : 03 March 2017
                : 27 March 2017
                Categories
                Epidemiology

                Oncology & Radiotherapy
                chances consortium,ageing,cohort,obesity,body fat distribution,cancer,prevention
                Oncology & Radiotherapy
                chances consortium, ageing, cohort, obesity, body fat distribution, cancer, prevention

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