Physical Activity, Sedentary Time and Breast Cancer Risk: A Mendelian Randomisation Study

Citation

Dixon-Suen, Suzanne C.; Lewis, Sarah J.; Martin, Richard M.; English, Dallas R.; Boyle, Terry; Giles, Graham G.; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; & Dennis, Joe, et al. (2022). Physical Activity, Sedentary Time and Breast Cancer Risk: A Mendelian Randomisation Study. British Journal of Sports Medicine, 56(20), 1157-1170. PMCID: PMC9876601

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,

URL

http://dx.doi.org/10.1136/bjsports-2021-105132

Reference Type

Journal Article

Year Published

2022

Journal Title

British Journal of Sports Medicine

Author(s)

Dixon-Suen, Suzanne C.
Lewis, Sarah J.
Martin, Richard M.
English, Dallas R.
Boyle, Terry
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 K.
Beane Freeman, Laura E.
Becher, Heiko
Beckmann, Matthias W.
Behrens, Sabine
Bermisheva, Marina
Blomqvist, Carl
Bogdanova, Natalia V.
Bojesen, Stig Egil
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 L.
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
Lubi
ński, Jan
Mannermaa, Arto
Manoochehri, Mehdi
Margolin, Sara
Martinez, Maria Elena
Mavroudis, Dimitrios
Menon, Usha
Mulligan, Anna Marie
Murphy, Rachel A.
NBCS
Collaborators,
Nevanlinna, Heli
Nevelsteen, Ines
Newman, William G.
Offit, Kenneth
Olshan, Andrew F.
Olsson, H
åkan
Orr, Nick
Patel, Alpa V.
Peto, Julian
Plaseska-Karanfilska, Dijana
Presneau, Nadege
Rack, Brigitte
Radice, Paolo
Rees-Punia, Erika
Rennert, Gad
Rennert, Hedy S.
Romero, Atocha
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 A. E. M.
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 D. P.
Easton, Douglas F.
Milne, Roger L.
Lynch, Brigid M.

Article Type

Regular

PMCID

PMC9876601

Data Set/Study

Breast Cancer Association Consortium (BCAC)
UK Biobank Study

Continent/Country

United States of America
United Kingdom

State

Nonspecific

Race/Ethnicity

European Ancestry

ORCiD

Olshan - 0000-0001-9115-5128