Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study.
Authors
Lewis, Sarah J
Martin, Richard M
English, Dallas R
Giles, Graham G
Michailidou, Kyriaki
Bolla, Manjeet K
Wang, Qin
Dennis, Joe
Lush, Michael
Investigators, Abctb
Ahearn, Thomas U
Ambrosone, Christine B
Andrulis, Irene L
Anton-Culver, Hoda
Arndt, Volker
Aronson, Kristan J
Augustinsson, Annelie
Auvinen, Päivi
Beane Freeman, Laura E
Becher, Heiko
Beckmann, Matthias W
Behrens, Sabine
Bermisheva, Marina
Blomqvist, Carl
Bogdanova, Natalia V
Bojesen, Stig E
Bonanni, Bernardo
Brenner, Hermann
Brüning, Thomas
Buys, Saundra S
Camp, Nicola J
Campa, Daniele
Canzian, Federico
Castelao, Jose E
Cessna, Melissa H
Chang-Claude, Jenny
Chanock, Stephen J
Clarke, Christine L
Conroy, Don M
Couch, Fergus J
Cox, Angela
Cross, Simon S
Czene, Kamila
Daly, Mary B
Devilee, Peter
Dörk, Thilo
Dwek, Miriam
Eccles, Diana M
Eliassen, A Heather
Engel, Christoph
Eriksson, Mikael
Evans, D Gareth
Fasching, Peter A
Fletcher, Olivia
Flyger, Henrik
Fritschi, Lin
Gabrielson, Marike
Gago-Dominguez, Manuela
García-Closas, Montserrat
García-Sáenz, José A
Goldberg, Mark S
Guénel, Pascal
Gündert, Melanie
Hahnen, Eric
Haiman, Christopher A
Häberle, Lothar
Håkansson, Niclas
Hall, Per
Hamann, Ute
Hart, Steven N
Harvie, Michelle
Hillemanns, Peter
Hollestelle, Antoinette
Hooning, Maartje J
Hoppe, Reiner
Hopper, John
Howell, Anthony
Hunter, David J
Jakubowska, Anna
Janni, Wolfgang
John, Esther M
Jung, Audrey
Kaaks, Rudolf
Keeman, Renske
Kitahara, Cari M
Koutros, Stella
Kraft, Peter
Kristensen, Vessela N
Kubelka-Sabit, Katerina
Kurian, Allison W
Lacey, James V
Lambrechts, Diether
Le Marchand, Loic
Lindblom, Annika
Loibl, Sibylle
Lubiński, Jan
Mannermaa, Arto
Manoochehri, Mehdi
Margolin, Sara
Martinez, Maria Elena
Mavroudis, Dimitrios
Menon, Usha
Mulligan, Anna Marie
Murphy, Rachel A
Collaborators, Nbcs
Nevanlinna, Heli
Nevelsteen, Ines
Newman, William G
Offit, Kenneth
Olshan, Andrew F
Olsson, Håkan
Orr, Nick
Patel, Alpa
Peto, Julian
Plaseska-Karanfilska, Dijana
Presneau, Nadege
Rack, Brigitte
Radice, Paolo
Rees-Punia, Erika
Rennert, Gad
Rennert, Hedy S
Saloustros, Emmanouil
Sandler, Dale P
Schmidt, Marjanka K
Schmutzler, Rita K
Schwentner, Lukas
Scott, Christopher
Shah, Mitul
Shu, Xiao-Ou
Simard, Jacques
Southey, Melissa C
Stone, Jennifer
Surowy, Harald
Swerdlow, Anthony J
Tamimi, Rulla M
Tapper, William J
Taylor, Jack A
Terry, Mary Beth
Tollenaar, Rob AEM
Troester, Melissa A
Truong, Thérèse
Untch, Michael
Vachon, Celine M
Joseph, Vijai
Wappenschmidt, Barbara
Weinberg, Clarice R
Wolk, Alicja
Yannoukakos, Drakoulis
Zheng, Wei
Ziogas, Argyrios
Dunning, Alison M
Pharoah, Paul DP
Easton, Douglas F
Milne, Roger L
Breast Cancer Association Consortium
Publication Date
2022-10Journal Title
Br J Sports Med
ISSN
0306-3674
Publisher
BMJ
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Dixon-Suen, S. C., Lewis, S. J., Martin, R. M., English, D. R., Boyle, T., Giles, G. G., Michailidou, K., et al. (2022). Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study.. Br J Sports Med https://doi.org/10.1136/bjsports-2021-105132
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 (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.
Keywords
Breast, Genetics, Physical activity, Sedentary Behaviour, Female, Humans, Breast Neoplasms, Exercise, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Risk Factors, Sedentary Behavior
Sponsorship
Cancer Research Uk (None)
Wellcome Trust (203477/Z/16/Z)
Medical Research Council (G1000143)
National Cancer Institute (U19CA148537)
National Cancer Institute (R01CA128978)
National Cancer Institute (U19CA148065)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Cancer Research UK (A10710)
Cancer Research UK (A16563)
Cancer Research UK (A12014)
Cancer Research UK (A10118)
National Cancer Institute (P30CA023100)
Medical Research Council (G0401527)
Medical Research Council (MR/N003284/1)
European Commission (223175)
Identifiers
External DOI: https://doi.org/10.1136/bjsports-2021-105132
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338752
Rights
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/
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