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Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis

N. Papadimitriou, N. Dimou, KK. Tsilidis, B. Banbury, RM. Martin, SJ. Lewis, N. Kazmi, TM. Robinson, D. Albanes, K. Aleksandrova, SI. Berndt, D. Timothy Bishop, H. Brenner, DD. Buchanan, B. Bueno-de-Mesquita, PT. Campbell, S. Castellví-Bel, AT....

. 2020 ; 11 (1) : 597. [pub] 20200130

Language English Country Great Britain

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Grant support
P30 ES010126 NIEHS NIH HHS - United States
U01 CA206110 NCI NIH HHS - United States
C18281/A19169 Cancer Research UK - United Kingdom
R01 CA201407 NCI NIH HHS - United States
S10 OD020069 NIH HHS - United States
P30 CA008748 NCI NIH HHS - United States
U01 CA167551 NCI NIH HHS - United States

Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.

Behavioral and Epidemiology Research Group American Cancer Society Atlanta GA USA

Bristol Medical School Department of Population Health Sciences University of Bristol Bristol UK

Cancer Epidemiology Unit Nuffield Department of Population Health University of Oxford OX3 7LF Oxford UK

Cancer Risk Factors and Life Style Epidemiology Unit Institute for Cancer Research Prevention and Clinical Network ISPRO Florence Italy

Center for Gastrointestinal Biology and Disease University of North Carolina Chapel Hill NC USA

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC Australia

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC Australia Cancer Epidemiology and Intelligence Division Cancer Council Victoria Melbourne VIC Australia

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC Australia Cancer Epidemiology and Intelligence Division Cancer Council Victoria Melbourne VIC Australia Genetic Epidemiology Laboratory Department of Pathology The University of Melbourne Parkville VIC Australia

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC Australia Cancer Epidemiology and Intelligence Division Cancer Council Victoria Melbourne VIC Australia Physical Activity Laboratory Baker Heart and Diabetes Institute Melbourne VIC Australia

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC Australia Colorectal Oncogenomics Group Genetic Epidemiology Laboratory Department of Pathology The University of Melbourne Parkville VIC Australia Genetic Medicine and Family Cancer Clinic The Royal Melbourne Hospital Parkville VIC Australia

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC Australia Department of Epidemiology School of Public Health and Institute of Health and Environment Seoul National University Seoul South Korea

CESP Fac de médecine Univ Paris Sud Fac de médecine UVSQ 1 Université Paris Saclay 94805 Villejuif France Gustave Roussy F 94805 Villejuif France

CESP Fac de médecine Univ Paris Sud Fac de médecine UVSQ 1 Université Paris Saclay 94805 Villejuif France Gustave Roussy F 94805 Villejuif France Laboratoire de Mathématiques Appliquées MAP5 Université Paris Descartes Paris France

CIBER de Epidemiología y Salud Pública Madrid Spain Andalusian School of Public Health Biomedical Research Institute ibs GRANADA University of Granada Granada Spain

CIBER de Epidemiología y Salud Pública Madrid Spain Cancer Prevention and Control Program Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Barcelona Spain Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain

CIBER de Epidemiología y Salud Pública Madrid Spain Department of Epidemiology Murcia Regional Health Council IMIB Arrixaca Murcia Spain

Clinical Genetics Service Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA Department of Medicine Weill Cornell Medical College New York NY USA

Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden

Department of Community Medicine and Epidemiology Lady Davis Carmel Medical Center Haifa Israel Ruth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa Israel Clalit National Cancer Control Center Haifa Israel

Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK

Department of Epidemiology Harvard T H Chan School of Public Health Harvard University Boston MA USA Department of Nutrition T H H Chan School of Public Health Boston MA USA Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA USA

Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Department of Family Medicine University of Virginia Charlottesville VA USA

Department of Health Science Research Mayo Clinic Scottsdale AZ USA

Department of Hygiene and Epidemiology University of Ioannina School of Medicine Ioannina Greece Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK

Department of Internal Medicine University of Utah Salt Lake City UT USA

Department of Medicine 1 University Hospital Dresden Technische Universität Dresden Dresden Germany

Department of Medicine and Epidemiology University of Pittsburgh Medical Center Pittsburgh PA USA

Department of Medicine Samuel Oschin Comprehensive Cancer Institute Cedars Sinai Medical Center Los Angeles CA USA Department of Preventive Medicine Keck School of Medicine University of Southern California Los Angeles CA USA

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Preventive Medicine USC Norris Comprehensive Cancer Center Keck School of Medicine University of Southern California Los Angeles CA USA

Department of Preventive Medicine USC Norris Comprehensive Cancer Center Keck School of Medicine University of Southern California Los Angeles CA USA Department of Cancer Epidemiology H Lee Moffitt Cancer Center and Research Institute Tampa FL USA

Department of Public Health and Primary Care University of Cambridge Cambridge UK

Department of Radiation Sciences Oncology Umea University 901 87 Umea Sweden

Department of Radiation Sciences Oncology Unit Umeå University Umeå Sweden Wallenberg Centre for Molecular Medicine Umeå University Umeå Sweden

Departments of Medicine and Genetics Case Comprehensive Cancer Center Case Western Reserve University and University Hospitals of Cleveland Cleveland OH USA

Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda MA USA

Division of Cancer Epidemiology German Cancer Research Center Hamburg Germany

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany

Division of Gastroenterology Massachusetts General Hospital and Harvard Medical School Boston MA USA Clinical and Translational Epidemiology Unit Massachusetts General Hospital and Harvard Medical School Boston MA USA

Division of Gastroenterology Massachusetts General Hospital and Harvard Medical School Boston MA USA Clinical and Translational Epidemiology Unit Massachusetts General Hospital and Harvard Medical School Boston MA USA Department of Epidemiology Harvard T H Chan School of Public Health Harvard University Boston MA USA Department of Nutrition T H H Chan School of Public Health Boston MA USA

Division of Human Genetics Department of Internal Medicine The Ohio State University Comprehensive Cancer Center Columbus OH USA

Division of Human Nutrition Wageningen University and Research Wageningen Netherlands

Division of Laboratory Genetics Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA

Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

Former senior scientist Dept for Determinants of Chronic Diseases PO Box 1 3720 BA Bilthoven Netherlands Former associate professor Department of Gastroenterology and Hepatology University Medical Centre Utrecht Netherlands Former visiting professor Dept of Epidemiology and Biostatistics The School of Public Health Imperial College London St Mary's Campus Norfolk Place London W2 1PG London UK Former academic Icon visiting professor Dept of Social and Preventive Medicine Faculty of Medicine University of Malaya Pantai Valley 50603 Kuala Lumpur Malaysia

Gastroenterology Department Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer University of Barcelona Barcelona Spain

German Institute of Human Nutrition Potsdam Rehbruecke Arthur Scheunert Allee 114 116 14558 Nuthetal Germany

Hellenic Health Foundation Athens Greece

Hellenic Health Foundation Athens Greece Dept of Clinical Sciences and Community Health Università degli Studi di Milano Milano Italy

Huntsman Cancer Institute and Department of Population Health Sciences University of Utah Salt Lake City UT USA

Institute of Cancer Research Department of Medicine 1 Medical University Vienna Vienna Austria

Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht University P O Box 85500 3508 GA UTRECHT Netherlands

Leeds Institute of Cancer and Pathology University of Leeds Leeds UK

Lunenfeld Tanenbaum Research Institute Mount Sinai Hospital University of Toronto Toronto ON Canada

Memorial University of Newfoundland Discipline of Genetics St John's Canada

MRC Integrative Epidemiology Unit Bristol Biomedical Research Centre University Hospitals Bristol NHS Foundation Trust and the University of Bristol Bristol UK

MRC Integrative Epidemiology Unit Population Health Sciences Bristol Medical School University of Bristol Bristol UK

Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA

Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA Department of Biostatistics University of Washington Seattle WA USA

Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA Department of Epidemiology University of Washington Seattle WA USA

Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA School of Public Health University of Washington Seattle WA USA

Section of Nutrition and Metabolism International Agency for Research on Cancer Lyon France

SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle WA USA

University of Hawaii Cancer Center Honolulu HI USA

University of Southern California Preventative Medicine Los Angeles CA USA

References provided by Crossref.org

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$a Brenner, Hermann $u Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
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$a Buchanan, Daniel D $u Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia.
700    1_
$a Bueno-de-Mesquita, Bas $u Former senior scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA, Bilthoven, Netherlands. Former associate professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. Former visiting professor, Dept. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, London, UK. Former academic Icon / visiting professor, Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, 50603, Kuala Lumpur, Malaysia.
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700    1_
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700    1_
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700    1_
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700    1_
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700    1_
$a Gallinger, Steven J $u Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
700    1_
$a Giles, Graham G $u Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia.
700    1_
$a Giovannucci, Edward $u Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. Department of Nutrition, T.H. H, Chan School of Public Health, Boston, MA, USA. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
700    1_
$a Gruber, Stephen B $u Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
700    1_
$a Gsur, Andrea $u Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.
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$a Hampe, Jochen $u Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
700    1_
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700    1_
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700    1_
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700    1_
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700    1_
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$a Hsu, Li $u Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Department of Biostatistics, University of Washington, Seattle, WA, USA.
700    1_
$a María Huerta, José $u CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
700    1_
$a Huyghe, Jeroen R $u Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
700    1_
$a Jenkins, Mark A $u Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
700    1_
$a Keku, Temitope O $u Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
700    1_
$a Kühn, Tilman $u Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
700    1_
$a La Vecchia, Carlo $u Hellenic Health Foundation, Athens, Greece. Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy.
700    1_
$a Le Marchand, Loic $u University of Hawaii Cancer Center, Honolulu, HI, USA.
700    1_
$a Li, Christopher I $u Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
700    1_
$a Li, Li $u Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.
700    1_
$a Lindblom, Annika $u Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
700    1_
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700    1_
$a Markowitz, Sanford D $u Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH, USA.
700    1_
$a Masala, Giovanna $u Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy.
700    1_
$a May, Anne M $u Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, 3508 GA, UTRECHT, Netherlands.
700    1_
$a Milne, Roger $u Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia. Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia.
700    1_
$a Monninkhof, Evelyn $u Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, 3508 GA, UTRECHT, Netherlands.
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700    1_
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$a Pharoah, Paul D P $u Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
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$a Platz, Elizabeth A $u Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
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$a Potter, John D $u Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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$a Rennert, Gad $u Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Clalit National Cancer Control Center, Haifa, Israel.
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$a Riboli, Elio $u Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
700    1_
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$a Schmit, Stephanie L $u Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
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$a Schoen, Robert E $u Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
700    1_
$a Severi, Gianluca $u CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ I, Université Paris-Saclay, 94805, Villejuif, France. Gustave Roussy, F-94805, Villejuif, France.
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$a Sieri, Sabina $u Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
700    1_
$a Slattery, Martha L $u Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
700    1_
$a Song, Mingyang $u Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. Department of Nutrition, T.H. H, Chan School of Public Health, Boston, MA, USA.
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$a Tangen, Catherine M $u SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
700    1_
$a Thibodeau, Stephen N $u Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
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$a Travis, Ruth C $u Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, OX3 7LF, Oxford, UK.
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700    1_
$a Ulrich, Cornelia M $u Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
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700    1_
$a Van Guelpen, Bethany $u Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden. Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
700    1_
$a Vodicka, Pavel $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic. Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
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$a White, Emily $u Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Department of Epidemiology, University of Washington, Seattle, WA, USA.
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$a Woods, Michael O $u Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
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$a Wu, Anna H $u University of Southern California, Preventative Medicine, Los Angeles, CA, USA.
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$a Peters, Ulrike $u Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Department of Epidemiology, University of Washington, Seattle, WA, USA.
700    1_
$a Gunter, Marc J $u Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
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