Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study,British Journal of Sports Medicine

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Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study
British Journal of Sports Medicine ( IF 18.4 ) Pub Date : 2022-10-01 , DOI: 10.1136/bjsports-2021-105132
Suzanne C Dixon-Suen ₁ , Sarah J Lewis _{2,

3} , Richard M Martin _{2,

3,

4} , Dallas R English _{1,

5} , Terry Boyle _{6,

7} , Graham G Giles _{1,

5,

8} , Kyriaki Michailidou _{9,

10} , Manjeet K Bolla ₁₁ , Qin Wang ₁₁ , Joe Dennis ₁₁ , Michael Lush ₁₁ , Abctb Investigators ₁₂ , Thomas U Ahearn ₁₃ , Christine B Ambrosone ₁₄ , Irene L Andrulis _{15,

16} , Hoda Anton-Culver ₁₇ , Volker Arndt ₁₈ , Kristan J Aronson ₁₉ , Annelie Augustinsson ₂₀ , Päivi Auvinen _{21,

22} , Laura E Beane Freeman ₁₃ , Heiko Becher ₂₃ , Matthias W Beckmann ₂₄ , Sabine Behrens ₂₅ , Marina Bermisheva ₂₆ , Carl Blomqvist _{27,

28} , Natalia V Bogdanova _{29,

30} , Stig E Bojesen _{31,

32} , Bernardo Bonanni ₃₃ , Hermann Brenner _{18,

34} , Thomas Brüning ₃₅ , Saundra S Buys ₃₆ , Nicola J Camp ₃₆ , Daniele Campa _{25,

37} , Federico Canzian ₃₈ , Jose E Castelao ₃₉ , Melissa H Cessna _{40,

41} , Jenny Chang-Claude _{25,

42} , Stephen J Chanock ₁₃ , Christine L Clarke ₄₃ , Don M Conroy ₄₄ , Fergus J Couch ₄₅ , Angela Cox ₄₆ , Simon S Cross ₄₇ , Kamila Czene ₄₈ , Mary B Daly ₄₉ , Peter Devilee _{50,

51} , Thilo Dörk ₃₀ , Miriam Dwek ₅₂ , Diana M Eccles ₅₃ , A Heather Eliassen _{54,

55} , Christoph Engel _{56,

57} , Mikael Eriksson ₄₈ , D Gareth Evans _{58,

59} , Peter A Fasching _{24,

60} , Olivia Fletcher ₆₁ , Henrik Flyger ₆₂ , Lin Fritschi ₆₃ , Marike Gabrielson ₄₈ , Manuela Gago-Dominguez _{64,

65} , Montserrat García-Closas ₁₃ , José A García-Sáenz ₆₆ , Mark S Goldberg _{67,

68} , Pascal Guénel ₆₉ , Melanie Gündert _{70,

71} , Eric Hahnen _{72,

73} , Christopher A Haiman ₇₄ , Lothar Häberle ₂₄ , Niclas Håkansson ₇₅ , Per Hall _{48,

76} , Ute Hamann ₇₇ , Steven N Hart ₇₈ , Michelle Harvie ₇₉ , Peter Hillemanns ₃₀ , Antoinette Hollestelle ₈₀ , Maartje J Hooning ₈₀ , Reiner Hoppe _{81,

82} , John Hopper ₅ , Anthony Howell ₈₃ , David J Hunter _{55,

84} , Anna Jakubowska _{85,

86} , Wolfgang Janni ₈₇ , Esther M John _{88,

89} , Audrey Jung ₂₅ , Rudolf Kaaks ₂₅ , Renske Keeman ₉₀ , Cari M Kitahara ₉₁ , Stella Koutros ₁₃ , Peter Kraft _{55,

92} , Vessela N Kristensen _{93,

94} , Katerina Kubelka-Sabit ₉₅ , Allison W Kurian _{88,

89} , James V Lacey _{96,

97} , Diether Lambrechts _{98,

99} , Loic Le Marchand ₁₀₀ , Annika Lindblom _{101,

102} , Sibylle Loibl ₁₀₃ , Jan Lubiński ₈₅ , Arto Mannermaa _{104,

105} , Mehdi Manoochehri ₇₇ , Sara Margolin _{76,

106} , Maria Elena Martinez _{65,

107} , Dimitrios Mavroudis ₁₀₈ , Usha Menon ₁₀₉ , Anna Marie Mulligan _{110,

111} , Rachel A Murphy _{112,

113} , Nbcs Collaborators _{93,

94} , Heli Nevanlinna ₁₁₄ , Ines Nevelsteen ₁₁₅ , William G Newman _{58,

59} , Kenneth Offit _{116,

117} , Andrew F Olshan ₁₁₈ , Håkan Olsson ₂₀ , Nick Orr ₁₁₉ , Alpa Patel ₁₂₀ , Julian Peto ₁₂₁ , Dijana Plaseska-Karanfilska ₁₂₂ , Nadege Presneau ₅₂ , Brigitte Rack ₈₇ , Paolo Radice ₁₂₃ , Erika Rees-Punia ₁₂₀ , Gad Rennert ₁₂₄ , Hedy S Rennert ₁₂₄ , Atocha Romero ₁₂₅ , Emmanouil Saloustros ₁₂₆ , Dale P Sandler ₁₂₇ , Marjanka K Schmidt _{90,

128} , Rita K Schmutzler _{72,

73} , Lukas Schwentner ₈₇ , Christopher Scott ₇₈ , Mitul Shah ₄₄ , Xiao-Ou Shu ₁₂₉ , Jacques Simard ₁₃₀ , Melissa C Southey _{1,

8} , Jennifer Stone _{5,

131} , Harald Surowy _{70,

71} , Anthony J Swerdlow _{132,

133} , Rulla M Tamimi _{55,

134} , William J Tapper ₅₃ , Jack A Taylor _{127,

135} , Mary Beth Terry ₁₃₆ , Rob A E M Tollenaar ₁₃₇ , Melissa A Troester ₁₁₈ , Thérèse Truong ₆₉ , Michael Untch ₁₃₈ , Celine M Vachon ₁₃₉ , Vijai Joseph ₁₁₆ , Barbara Wappenschmidt _{72,

73} , Clarice R Weinberg ₁₄₀ , Alicja Wolk _{75,

141} , Drakoulis Yannoukakos ₁₄₂ , Wei Zheng ₁₂₉ , Argyrios Ziogas ₁₇ , Alison M Dunning ₄₄ , Paul D P Pharoah _{11,

44} , Douglas F Easton _{11,

44} , Roger L Milne _{1,

5,

8} , Brigid M Lynch _{5,

143,

144} ,

Affiliation

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
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.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
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.
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
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.
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
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.
Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, California, USA.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
Department of Oncology, Cancer Center, Kuopio University Hospital, Kuopio, Finland.
Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland.
Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Biochemistry and Genetics, FSBSI Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russian Federation.
Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Department of Oncology, Örebro University Hospital, Örebro, Sweden.
Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
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.
Division of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Milan, Italy.
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr University Bochum, Bochum, Germany.
Department of Internal Medicine and Huntsman Cancer Institute, The University of Utah, Salt Lake City, Utah, USA.
Department of Biology, University of Pisa, Pisa, Italy.
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Oncology and Genetics Unit, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain.
Department of Pathology, Intermountain Medical Center, Intermountain Healthcare, Salt Lake City, Utah, USA.
Intermountain Biorepository, Intermountain Healthcare, Salt Lake City, Utah, USA.
Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, The University of Sheffield, Sheffield, UK.
Academic Unit of Pathology, Department of Neuroscience, The University of Sheffield, Sheffield, UK.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
School of Life Sciences, University of Westminster, London, UK.
Faculty of Medicine, University of Southampton, Southampton, UK.
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.
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany.
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.
David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California Los Angeles, Los Angeles, California, USA.
The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
School of Population Health, Curtin University, Perth, Western Australia, Australia.
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.
Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain.
Department of Medicine, McGill University, Montréal, Québec, Canada.
Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montréal, Québec, Canada.
Team 'Exposome and Heredity', Center for Research in Epidemiology and Population Health (CESP), Gustave Roussy, INSERM, University Paris-Saclay, Villejuif, France.
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.
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.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology, Södersjukhuset, Stockholm, Sweden.
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Prevent Breast Cancer Research Unit, Manchester University Hospital Foundation NHS Trust, Manchester, UK.
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
University of Tübingen, Tübingen, Germany.
Division of Cancer Sciences, The University of Manchester, Manchester, UK.
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
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.
Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
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.
Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
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.
Department of Histopathology and Cytology, Clinical Hospital Acibadem Sistina, Skopje, Macedonia (the former Yugoslav Republic of).
Department of Computational and Quantitative Medicine, City of Hope, Duarte, California, USA.
City of Hope Comprehensive Cancer Center, City of Hope, Duarte, California, USA.
VIB Center for Cancer Biology, VIB, Gent, Oost-Vlaanderen, Belgium.
Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, Hawaii, USA.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
German Breast Group, Neu-Isenburg, Germany.
Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, USA.
Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece.
MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
Cancer Control Research, BC Cancer, Vancouver, British Columbia, Canada.
School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada.
Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
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.
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.
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
Department of Population Science, American Cancer Society, Atlanta, Georgia, USA.
Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', MASA, Skopje, Macedonia (the former Yugoslav Republic of).
Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Department of Oncology, University Hospital of Larissa, Larissa, Greece.
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA.
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval Research Center, Québec City, Québec, Canada.
Genetic Epidemiology Group, School of Population and Global Health, The University of Western Australia, Perth, Western Australia, Australia.
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
Department of Population Health Sciences, Weill Cornell Medicine, New York City, New York, USA.
Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA.
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, New York, USA.
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Department of Gynecology and Obstetrics, Helios Clinics Berlin-Buch, Berlin, Germany.
Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA.
Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA.
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research-Demokritos, Athens, Greece.
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

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 (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=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. Data are available upon reasonable request. The data used in this study are de-identified patient data from 76 studies participating in the Breast Cancer Association Consortium (BCAC). Enquiries about accessing BCAC data can be directed to the BCAC coordinators at the University of Cambridge:

中文翻译：

体力活动、久坐时间和乳腺癌风险：孟德尔随机研究

目的在观察性研究中，缺乏身体活动和久坐行为与较高的乳腺癌风险相关，但很难确定因果关系。孟德尔随机化 (MR) 通过使用基因型模拟随机试验组来评估因果关系。我们评估了使用基因型评估的终生体力活动或久坐时间是否可能与绝经前/绝经后的总体乳腺癌风险存在因果关系，并按肿瘤特征定义的病例组进行了评估。方法我们使用来自 130 957 名欧洲血统女性（69 838 例侵入性病例）的个体水平乳腺癌协会联盟病例对照数据进行了两样本逆方差加权 MR，并发表了英国生物库数据（n=91 105-377） 234）。遗传仪器是英国生物银行中与腕戴式加速度计测量的整体身体活动 (nsnps=5) 或久坐时间 (nsnps=6) 或加速度计测量 (nsnps=1) 或自我报告相关的单核苷酸多态性 (SNP) (nsnps=5) 剧烈的体力活动。结果对于大多数病例组而言，较高的基因预测总体活动与较低的乳腺癌总体风险相关（OR = 0.59；95% 置信区间 (CI) 每个标准差为 0.42 至 0.83（SD；~8 毫重力加速度））。基因预测的剧烈活动与绝经前/围绝经期乳腺癌风险较低相关（OR = 0.62；95% CI 0.45 至 0.87，自我报告的每周≥3 天 vs. 0 天），与大多数病例组的估计一致。遗传预测的久坐时间越长，激素受体阴性肿瘤风险越高（OR = 1.77；95% CI 1.07 至 2.92 per-SD（约 7% 久坐时间）），大多数病例组的估计值较高。结果对于检查多效性（包括加权中值 MR、MR-Egger）的敏感性分析是稳健的。结论我们的研究提供了强有力的证据，表明更多的整体体力活动、更大的剧烈活动和更少的久坐时间可能会降低乳腺癌风险。更广泛地采用积极的生活方式可能会减轻女性最常见癌症的负担。数据可根据合理要求提供。本研究中使用的数据是来自参与乳腺癌协会联盟 (BCAC) 的 76 项研究的去识别化患者数据。

更新日期：2022-09-29

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