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

Dixon-Suen, Suzanne C and Lewis, Sarah J and Martin, Richard M and English, Dallas R and Boyle, Terry and Giles, Graham G and Michailidou, Kyriaki and Bolla, Manjeet K and Wang, Qin and Dennis, Joe and Lush, Michael and Investigators, Abctb and Ahearn, Thomas U and Ambrosone, Christine B and Andrulis, Irene L and Anton-Culver, Hoda and Arndt, Volker and Aronson, Kristan J and Augustinsson, Annelie and Auvinen, Päivi and Beane Freeman, Laura E and Becher, Heiko and Beckmann, Matthias W and Behrens, Sabine and Bermisheva, Marina and Blomqvist, Carl and Bogdanova, Natalia V and Bojesen, Stig E and Bonanni, Bernardo and Brenner, Hermann and Brüning, Thomas and Buys, Saundra S and Camp, Nicola J and Campa, Daniele and Canzian, Federico and Castelao, Jose E and Cessna, Melissa H and Chang-Claude, Jenny and Chanock, Stephen J and Clarke, Christine L and Conroy, Don M and Couch, Fergus J and Cox, Angela and Cross, Simon S and Czene, Kamila and Daly, Mary B and Devilee, Peter and Dörk, Thilo and Dwek, Miriam and Eccles, Diana M and Eliassen, A Heather and Engel, Christoph and Eriksson, Mikael and Evans, D Gareth and Fasching, Peter A and Fletcher, Olivia and Flyger, Henrik and Fritschi, Lin and Gabrielson, Marike and Gago-Dominguez, Manuela and García-Closas, Montserrat and García-Sáenz, José A and Goldberg, Mark S and Guénel, Pascal and Gündert, Melanie and Hahnen, Eric and Haiman, Christopher A and Häberle, Lothar and Håkansson, Niclas and Hall, Per and Hamann, Ute and Hart, Steven N and Harvie, Michelle and Hillemanns, Peter and Hollestelle, Antoinette and Hooning, Maartje J and Hoppe, Reiner and Hopper, John and Howell, Anthony and Hunter, David J and Jakubowska, Anna and Janni, Wolfgang and John, Esther M and Jung, Audrey and Kaaks, Rudolf and Keeman, Renske and Kitahara, Cari M and Koutros, Stella and Kraft, Peter and Kristensen, Vessela N and Kubelka-Sabit, Katerina and Kurian, Allison W and Lacey, James V and Lambrechts, Diether and Le Marchand, Loic and Lindblom, Annika and Loibl, Sibylle and Lubiński, Jan and Mannermaa, Arto and Manoochehri, Mehdi and Margolin, Sara and Martinez, Maria Elena and Mavroudis, Dimitrios and Menon, Usha and Mulligan, Anna Marie and Murphy, Rachel A and Collaborators, Nbcs and Nevanlinna, Heli and Nevelsteen, Ines and Newman, William G and Offit, Kenneth and Olshan, Andrew F and Olsson, Håkan and Orr, Nick and Patel, Alpa and Peto, Julian and Plaseska-Karanfilska, Dijana and Presneau, Nadege and Rack, Brigitte and Radice, Paolo and Rees-Punia, Erika and Rennert, Gad and Rennert, Hedy S and Romero, Atocha and Saloustros, Emmanouil and Sandler, Dale P and Schmidt, Marjanka K and Schmutzler, Rita K and Schwentner, Lukas and Scott, Christopher and Shah, Mitul and Shu, Xiao-Ou and Simard, Jacques and Southey, Melissa C and Stone, Jennifer and Surowy, Harald and Swerdlow, Anthony J and Tamimi, Rulla M and Tapper, William J and Taylor, Jack A and Terry, Mary Beth and Tollenaar, Rob A E M and Troester, Melissa A and Truong, Thérèse and Untch, Michael and Vachon, Celine M and Joseph, Vijai and Wappenschmidt, Barbara and Weinberg, Clarice R and Wolk, Alicja and Yannoukakos, Drakoulis and Zheng, Wei and Ziogas, Argyrios and Dunning, Alison M and Pharoah, Paul D P and Easton, Douglas F and Milne, Roger L and Lynch, Brigid M (2022) Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study. British journal of sports medicine, 56 (20). pp. 1157-1170. ISSN 1473-0480

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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.


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=5) or sedentary time (n=6), or accelerometer-measured (n=1) or self-reported (n=5) vigorous physical activity.


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).


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.

Item Type: Article
Impact Factor Value: 18.473
Subjects: Medical and Health Sciences > Basic medicine
Medical and Health Sciences > Clinical medicine
Divisions: Faculty of Medical Science
Depositing User: Katerina Kubelka-Sabit
Date Deposited: 16 Jan 2023 12:10
Last Modified: 16 Jan 2023 12:10

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