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

Suzanne C. Dixon-Suen, Sarah J. Lewis, Richard M. Martin, Dallas R. English, Terry Boyle, Graham G. Giles, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang, Joe Dennis, Michael Lush, Abctb Investigators, Thomas U. Ahearn, Christine B. Ambrosone, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J. Aronson, Annelie Augustinsson, Päivi AuvinenLaura E.Beane Freeman, Heiko Becher, Matthias W. Beckmann, Sabine Behrens, Marina Bermisheva, Carl Blomqvist, Natalia V. Bogdanova, Stig E. Bojesen, Bernardo Bonanni, Hermann Brenner, Thomas Brüning, Saundra S. Buys, Nicola J. Camp, Daniele Campa, Federico Canzian, Jose E. Castelao, Melissa H. Cessna, Jenny Chang-Claude, Stephen J. Chanock, Christine L. Clarke, Don M. Conroy, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Miriam Dwek, Diana M. Eccles, A. Heather Eliassen, Christoph Engel, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Lin Fritschi, Marike Gabrielson, Manuela Gago-Dominguez, Montserrat García-Closas, José A. García-Sáenz, Mark S. Goldberg, Pascal Guénel, Melanie Gündert, Eric Hahnen, Christopher A. Haiman, Lothar Häberle, Niclas Håkansson, Per Hall, Ute Hamann, Steven N. Hart, Michelle Harvie, Peter Hillemanns, Antoinette Hollestelle, Maartje J. Hooning, Reiner Hoppe, John Hopper, Anthony Howell, David J. Hunter, Anna Jakubowska, Wolfgang Janni, Esther M. John, Audrey Jung, Rudolf Kaaks, Renske Keeman, Cari M. Kitahara, Stella Koutros, Peter Kraft, Vessela N. Kristensen, Katerina Kubelka-Sabit, Allison W. Kurian, James V. Lacey, Diether Lambrechts, Loic Le Marchand, Annika Lindblom, Sibylle Loibl, Jan Lubiński, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Maria Elena Martinez, Dimitrios Mavroudis, Usha Menon, Anna Marie Mulligan, Rachel A. Murphy, Nbcs Collaborators, Heli Nevanlinna, Ines Nevelsteen, William G. Newman, Kenneth Offit, Andrew F. Olshan, Håkan Olsson, Nick Orr, Alpa Patel, Julian Peto, Dijana Plaseska-Karanfilska, Nadege Presneau, Brigitte Rack, Paolo Radice, Erika Rees-Punia, Gad Rennert, Hedy S. Rennert, Atocha Romero, Emmanouil Saloustros, Dale P. Sandler, Marjanka K. Schmidt, Rita K. Schmutzler, Lukas Schwentner, Christopher Scott, Mitul Shah, Xiao Ou Shu, Jacques Simard, Melissa C. Southey, Jennifer Stone, Harald Surowy, Anthony J. Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Mary Beth Terry, Rob A.E.M. Tollenaar, Melissa A. Troester, Thérèse Truong, Michael Untch, Celine M. Vachon, Vijai Joseph, Barbara Wappenschmidt, Clarice R. Weinberg, Alicja Wolk, Drakoulis Yannoukakos, Wei Zheng, Argyrios Ziogas, Alison M. Dunning, Paul D.P. Pharoah, Douglas F. Easton, Roger L. Milne, Brigid M. Lynch

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1157-1170
Number of pages14
JournalBritish journal of sports medicine
Volume56
Issue number20
DOIs
StatePublished - Sep 6 2022

Keywords

  • Breast
  • Genetics
  • Physical activity
  • Sedentary Behaviour

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

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