Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study.

Autor:	Dixon-Suen SC; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia., Lewis SJ; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK., Martin RM; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; NIHR Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK., English DR; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia., Boyle T; Allied Health and Human Performance, University of South Australia, Adelaide, South Australia, Australia.; Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, South Australia, Australia., Giles GG; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia., Michailidou K; Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.; Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Bolla MK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Wang Q; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Dennis J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Lush M; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Investigators A; Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia., Ahearn TU; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Ambrosone CB; Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA., Andrulis IL; Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Anton-Culver H; Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, California, USA., Arndt V; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Aronson KJ; Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, Ontario, Canada., Augustinsson A; Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden., Auvinen P; Department of Oncology, Cancer Center, Kuopio University Hospital, Kuopio, Finland.; Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland., Beane Freeman LE; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Becher H; Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Beckmann MW; Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany., Behrens S; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Bermisheva M; Institute of Biochemistry and Genetics, FSBSI Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russian Federation., Blomqvist C; Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.; Department of Oncology, Örebro University Hospital, Örebro, Sweden., Bogdanova NV; Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Bojesen SE; Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark., Bonanni B; Division of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Milan, Italy., Brenner H; 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., Brüning T; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr University Bochum, Bochum, Germany., Buys SS; Department of Internal Medicine and Huntsman Cancer Institute, The University of Utah, Salt Lake City, Utah, USA., Camp NJ; Department of Internal Medicine and Huntsman Cancer Institute, The University of Utah, Salt Lake City, Utah, USA., Campa D; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Biology, University of Pisa, Pisa, Italy., Canzian F; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany., Castelao JE; Oncology and Genetics Unit, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain., Cessna MH; Department of Pathology, Intermountain Medical Center, Intermountain Healthcare, Salt Lake City, Utah, USA.; Intermountain Biorepository, Intermountain Healthcare, Salt Lake City, Utah, USA., Chang-Claude J; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Clarke CL; Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia., Conroy DM; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Couch FJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Cox A; Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, The University of Sheffield, Sheffield, UK., Cross SS; Academic Unit of Pathology, Department of Neuroscience, The University of Sheffield, Sheffield, UK., Czene K; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Daly MB; Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA., Devilee P; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., Dörk T; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Dwek M; School of Life Sciences, University of Westminster, London, UK., Eccles DM; Faculty of Medicine, University of Southampton, Southampton, UK., Eliassen AH; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Engel C; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.; LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany., Eriksson M; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Evans DG; Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Fasching PA; Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.; David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California Los Angeles, Los Angeles, California, USA., Fletcher O; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK., Flyger H; Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark., Fritschi L; School of Population Health, Curtin University, Perth, Western Australia, Australia., Gabrielson M; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Gago-Dominguez M; Genomic Medicine Group, International Cancer Genetics and Epidemiology Group, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain.; Moores Cancer Center, University of California San Diego, La Jolla, California, USA., García-Closas M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., García-Sáenz JA; Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain., Goldberg MS; Department of Medicine, McGill University, Montréal, Québec, Canada.; Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montréal, Québec, Canada., Guénel P; Team 'Exposome and Heredity', Center for Research in Epidemiology and Population Health (CESP), Gustave Roussy, INSERM, University Paris-Saclay, Villejuif, France., Gündert M; Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, University of Heidelberg, Heidelberg, Germany., Hahnen E; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Haiman CA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Häberle L; Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany., Håkansson N; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden., Hall P; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Department of Oncology, Södersjukhuset, Stockholm, Sweden., Hamann U; Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Hart SN; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Harvie M; Prevent Breast Cancer Research Unit, Manchester University Hospital Foundation NHS Trust, Manchester, UK., Hillemanns P; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Hollestelle A; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Hooning MJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Hoppe R; Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.; University of Tübingen, Tübingen, Germany., Hopper J; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia., Howell A; Division of Cancer Sciences, The University of Manchester, Manchester, UK., Hunter DJ; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Nuffield Department of Population Health, University of Oxford, Oxford, UK., Jakubowska A; Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.; Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University in Szczecin, Szczecin, Poland., Janni W; Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany., John EM; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, USA.; Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA., Jung A; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Kaaks R; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Keeman R; Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Kitahara CM; Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA., Koutros S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Kraft P; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Kristensen VN; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Kubelka-Sabit K; Department of Histopathology and Cytology, Clinical Hospital Acibadem Sistina, Skopje, Macedonia (the former Yugoslav Republic of)., Kurian AW; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, USA.; Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA., Lacey JV; Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA.; City of Hope Comprehensive Cancer Center, City of Hope, Duarte, California, USA., Lambrechts D; VIB Center for Cancer Biology, VIB, Gent, Oost-Vlaanderen, Belgium.; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Le Marchand L; Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, Hawaii, USA., Lindblom A; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden., Loibl S; German Breast Group, Neu-Isenburg, Germany., Lubiński J; Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland., Mannermaa A; Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.; Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland., Manoochehri M; Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Margolin S; Department of Oncology, Södersjukhuset, Stockholm, Sweden.; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden., Martinez ME; Moores Cancer Center, University of California San Diego, La Jolla, California, USA.; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA., Mavroudis D; Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece., Menon U; MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK., Mulligan AM; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.; Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada., Murphy RA; Cancer Control Research, BC Cancer, Vancouver, British Columbia, Canada.; School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada., Collaborators N; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Nevanlinna H; Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland., Nevelsteen I; Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium., Newman WG; Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Offit K; Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York City, New York, USA.; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA., Olshan AF; Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Olsson H; Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden., Orr N; Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK., Patel A; Department of Population Science, American Cancer Society, Atlanta, Georgia, USA., Peto J; Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK., Plaseska-Karanfilska D; Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', MASA, Skopje, Macedonia (the former Yugoslav Republic of)., Presneau N; School of Life Sciences, University of Westminster, London, UK., Rack B; Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany., Radice P; Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Rees-Punia E; Department of Population Science, American Cancer Society, Atlanta, Georgia, USA., Rennert G; Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel., Rennert HS; Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel., Romero A; Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain., Saloustros E; Department of Oncology, University Hospital of Larissa, Larissa, Greece., Sandler DP; Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA., Schmidt MK; Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.; Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Schmutzler RK; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Schwentner L; Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany., Scott C; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Shah M; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Shu XO; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Simard J; Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval Research Center, Québec City, Québec, Canada., Southey MC; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia., Stone J; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Genetic Epidemiology Group, School of Population and Global Health, The University of Western Australia, Perth, Western Australia, Australia., Surowy H; Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, University of Heidelberg, Heidelberg, Germany., Swerdlow AJ; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.; Division of Breast Cancer Research, The Institute of Cancer Research, London, UK., Tamimi RM; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Department of Population Health Sciences, Weill Cornell Medicine, New York City, New York, USA., Tapper WJ; Faculty of Medicine, University of Southampton, Southampton, UK., Taylor JA; Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA.; Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA., Terry MB; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, New York, USA., Tollenaar RAEM; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands., Troester MA; Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Truong T; Team 'Exposome and Heredity', Center for Research in Epidemiology and Population Health (CESP), Gustave Roussy, INSERM, University Paris-Saclay, Villejuif, France., Untch M; Department of Gynecology and Obstetrics, Helios Clinics Berlin-Buch, Berlin, Germany., Vachon CM; Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA., Joseph V; Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York City, New York, USA., Wappenschmidt B; Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Weinberg CR; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA., Wolk A; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden., Yannoukakos D; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research-Demokritos, Athens, Greece., Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Ziogas A; Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, California, USA., Dunning AM; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Pharoah PDP; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Easton DF; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Milne RL; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia., Lynch BM; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia brigid.lynch@cancervic.org.au.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Jazyk:	angličtina
Zdroj:	British journal of sports medicine [Br J Sports Med] 2022 Oct; Vol. 56 (20), pp. 1157-1170. Date of Electronic Publication: 2022 Sep 06.
DOI:	10.1136/bjsports-2021-105132
Abstrakt:	Objectives: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics. Methods: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (n snps =5) or sedentary time (n snps =6), or accelerometer-measured (n snps =1) or self-reported (n snps =5) vigorous physical activity. Results: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). Conclusion: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women. Competing Interests: Competing interests: MWB conducts research funded by Amgen, Novartis and Pfizer. PAF conducts research funded by Amgen, Novartis and Pfizer. He received honoraria from Roche, Novartis and Pfizer. AWK declares research funding to her institution from Myriad Genetics for an unrelated project (funding dates 2017-2019). SL declares grants and honoraria paid to her institution from Amgen, Novartis, Pfizer, Roche, and, outside the submitted work, grants and/or honoraria paid to her institution from AbbVie, Celgene, Seattle Genetics, PrIME/Medscape, Daiichi-Sankyo, Lilly, Samsung, BMS, Puma, Immunomedics, AstraZeneca, Pierre Fabre, Merck, GlaxoSmithKlein, EirGenix, and Bayer, and personal fees from Chugai; SL also has a patent EP14153692.0 pending. UM declares stock ownership in Abcodia Ltd. RAM has been a consultant for Pharmavite. No other authors have conflicts to declare. (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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