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.
Original language | English |
---|---|
Article number | 105132 |
Pages (from-to) | 1157-1170 |
Number of pages | 14 |
Journal | British Journal of Sports Medicine |
Volume | 56 |
Issue number | 20 |
DOIs | |
Publication status | Published - Oct 2022 |
Keywords
- Breast
- Genetics
- Physical activity
- Sedentary Behaviour
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In: British Journal of Sports Medicine, Vol. 56, No. 20, 105132, 10.2022, p. 1157-1170.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Physical activity, sedentary time and breast cancer risk
T2 - A Mendelian randomisation study
AU - Dixon-Suen, Suzanne C.
AU - Lewis, Sarah J.
AU - Martin, Richard M.
AU - English, Dallas R.
AU - Boyle, Terry
AU - Giles, Graham G.
AU - Michailidou, Kyriaki
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Dennis, Joe
AU - Lush, Michael
AU - Ahearn, Thomas U.
AU - Ambrosone, Christine B.
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Aronson, Kristan J.
AU - Augustinsson, Annelie
AU - Auvinen, Päivi
AU - Beane Freeman, Laura E.
AU - Becher, Heiko
AU - Beckmann, Matthias W.
AU - Behrens, Sabine
AU - Bermisheva, Marina
AU - Blomqvist, Carl
AU - Bogdanova, Natalia V.
AU - Bojesen, Stig E.
AU - Bonanni, Bernardo
AU - Brenner, Hermann
AU - Brüning, Thomas
AU - Buys, Saundra S.
AU - Camp, Nicola J.
AU - Campa, Daniele
AU - Canzian, Federico
AU - Castelao, Jose E.
AU - Cessna, Melissa H.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Clarke, Christine L.
AU - Conroy, Don M.
AU - Couch, Fergus J.
AU - Cox, Angela
AU - Cross, Simon S.
AU - Czene, Kamila
AU - Daly, Mary
AU - Devilee, Peter
AU - Dörk, Thilo
AU - Dwek, Miriam
AU - Eccles, Diana M.
AU - Eliassen, A. Heather
AU - Engel, Christoph
AU - Eriksson, Mikael
AU - Evans, D. Gareth
AU - Fasching, Peter A.
AU - Fletcher, Olivia
AU - Flyger, Henrik
AU - Fritschi, Lin
AU - Gabrielson, Marike
AU - Gago-Dominguez, Manuela
AU - García-Closas, Montserrat
AU - García-Sáenz, José A.
AU - Goldberg, Mark S.
AU - Guénel, Pascal
AU - Gündert, Melanie
AU - Hahnen, Eric
AU - Haiman, Christopher A.
AU - Häberle, Lothar
AU - Håkansson, Niclas
AU - Hall, Per
AU - Hamann, Ute
AU - Hart, Steven N.
AU - Harvie, Michelle
AU - Hillemanns, Peter
AU - Hollestelle, Antoinette
AU - Hooning, Maartje J.
AU - Hoppe, Reiner
AU - Hopper, John
AU - Howell, Anthony
AU - Hunter, David J.
AU - Jakubowska, Anna
AU - Janni, Wolfgang
AU - John, Esther M.
AU - Jung, Audrey
AU - Kaaks, Rudolf
AU - Keeman, Renske
AU - Kitahara, Cari M.
AU - Koutros, Stella
AU - Kraft, Peter
AU - Kristensen, Vessela N.
AU - Kubelka-Sabit, Katerina
AU - Kurian, Allison W.
AU - Lacey, James V.
AU - Lambrechts, Diether
AU - Le Marchand, Loic
AU - Lindblom, Annika
AU - Loibl, Sibylle
AU - Lubiński, Jan
AU - Mannermaa, Arto
AU - Manoochehri, Mehdi
AU - Margolin, Sara
AU - Martinez, Maria Elena
AU - Mavroudis, Dimitrios
AU - Menon, Usha
AU - Mulligan, Anna Marie
AU - Murphy, Rachel A.
AU - Nevanlinna, Heli
AU - Nevelsteen, Ines
AU - Newman, William G.
AU - Offit, Kenneth
AU - Olshan, Andrew F.
AU - Olsson, Håkan
AU - Orr, Nick
AU - Patel, Alpa
AU - Peto, Julian
AU - Plaseska-Karanfilska, Dijana
AU - Presneau, Nadege
AU - Rack, Brigitte
AU - Radice, Paolo
AU - Rees-Punia, Erika
AU - Rennert, Gad
AU - Rennert, Hedy S.
AU - Romero, Atocha
AU - Saloustros, Emmanouil
AU - Sandler, Dale P.
AU - Schmidt, Marjanka K.
AU - Schmutzler, Rita K.
AU - Schwentner, Lukas
AU - Scott, Christopher
AU - Shah, Mitul
AU - Shu, Xiao-Ou
AU - Simard, Jacques
AU - Southey, Melissa C.
AU - Stone, Jennifer
AU - Surowy, Harald
AU - Swerdlow, Anthony J.
AU - Tamimi, Rulla M.
AU - Tapper, William J.
AU - Taylor, Jack A.
AU - Terry, Mary Beth
AU - Tollenaar, Rob A.E.M.
AU - Troester, Melissa A.
AU - Truong, Thérèse
AU - Untch, Michael
AU - Vachon, Celine M.
AU - Joseph, Vijai
AU - Wappenschmidt, Barbara
AU - Weinberg, Clarice R.
AU - Wolk, Alicja
AU - Yannoukakos, Drakoulis
AU - Zheng, Wei
AU - Ziogas, Argyrios
AU - Dunning, Alison M.
AU - Pharoah, Paul D.P.
AU - Easton, Douglas F.
AU - Milne, Roger L.
AU - Lynch, Brigid M.
AU - ABCTB Investigators
AU - NBCS Collaborators
AU - on behalf of the Breast Cancer Association Consortium
N1 - Funding Information: MWB conducts research funded by Amgen, Novartis and Pfizer. PAF conducts research funded by Amgen, Novartis and Pfizer. He received honoraria from Roche, Novartis and Pfizer. AWK declares research funding to her institution from Myriad Genetics for an unrelated project (funding dates 2017-2019). SL declares grants and honoraria paid to her institution from Amgen, Novartis, Pfizer, Roche, and, outside the submitted work, grants and/or honoraria paid to her institution from AbbVie, Celgene, Seattle Genetics, PrIME/Medscape, Daiichi-Sankyo, Lilly, Samsung, BMS, Puma, Immunomedics, AstraZeneca, Pierre Fabre, Merck, GlaxoSmithKlein, EirGenix, and Bayer, and personal fees from Chugai; SL also has a patent EP14153692.0 pending. UM declares stock ownership in Abcodia Ltd. RAM has been a consultant for Pharmavite. No other authors have conflicts to declare. Publisher Copyright: © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - Breast
KW - Genetics
KW - Physical activity
KW - Sedentary Behaviour
UR - http://www.scopus.com/inward/record.url?scp=85137660444&partnerID=8YFLogxK
U2 - 10.1136/bjsports-2021-105132
DO - 10.1136/bjsports-2021-105132
M3 - Article
C2 - 36328784
AN - SCOPUS:85137660444
SN - 0306-3674
VL - 56
SP - 1157
EP - 1170
JO - British Journal of Sports Medicine
JF - British Journal of Sports Medicine
IS - 20
M1 - 105132
ER -