Physical activity, sedentary time and breast cancer risk: A Mendelian randomisation study Journal Article


Authors: Dixon-Suen, S. C.; Lewis, S. J.; Martin, R. M.; English, D. R.; Boyle, T.; Giles, G. G.; Michailidou, K.; Bolla, M. K.; Wang, Q.; Dennis, J.; Lush, M.; ABCTB Investigators; Ahearn, T. U.; Ambrosone, C. B.; Andrulis, I. L.; Anton-Culver, H.; Arndt, V.; Aronson, K. J.; Augustinsson, A.; Auvinen, P.; Freeman, L. E. B.; Becher, H.; Beckmann, M. W.; Behrens, S.; Bermisheva, M.; Blomqvist, C.; Bogdanova, N. V.; Bojesen, S. E.; Bonanni, B.; Brenner, H.; Brüning, T.; Buys, S. S.; Camp, N. J.; Campa, D.; Canzian, F.; Castelao, J. E.; Cessna, M. H.; Chang-Claude, J.; Chanock, S. J.; Clarke, C. L.; Conroy, D. M.; Couch, F. J.; Cox, A.; Cross, S. S.; Czene, K.; Daly, M. B.; Devilee, P.; Dörk, T.; Dwek, M.; Eccles, D. M.; Eliassen, A. H.; Engel, C.; Eriksson, M.; Evans, D. G.; Fasching, P. A.; Fletcher, O.; Flyger, H.; Fritschi, L.; Gabrielson, M.; Gago-Dominguez, M.; Garcia-Closas, M.; García-Sáenz, J. A.; Goldberg, M. S.; Guénel, P.; Gundert, M.; Hahnen, E.; Haiman, C. A.; Haberle, L.; Håkansson, N.; Hall, P.; Hamann, U.; Hart, S. N.; Harvie, M.; Hillemanns, P.; Hollestelle, A.; Hooning, M. J.; Hoppe, R.; Hopper, J.; Howell, A.; Hunter, D. J.; Jakubowska, A.; Janni, W.; John, E. M.; Jung, A.; Kaaks, R.; Keeman, R.; Kitahara, C. M.; Koutros, S.; Kraft, P.; Kristensen, V. N.; Kubelka-Sabit, K.; Kurian, A. W.; Lacey, J. V.; Lambrechts, D.; Le Marchand, L.; Lindblom, A.; Loibl, S.; Lubiński, J.; Mannermaa, A.; Manoochehri, M.; Margolin, S.; Martinez, M. E.; Mavroudis, D.; Menon, U.; Mulligan, A. M.; Murphy, R. A.; NBCS Collaborators; Nevanlinna, H.; Nevelsteen, I.; Newman, W. G.; Offit, K.; Olshan, A. F.; Olsson, H.; Orr, N.; Patel, A.; Peto, J.; Plaseska-Karanfilska, D.; Presneau, N.; Rack, B.; Radice, P.; Rees-Punia, E.; Rennert, G.; Rennert, H. S.; Romero, A.; Saloustros, E.; Sandler, D. P.; Schmidt, M. K.; Schmutzler, R. K.; Schwentner, L.; Scott, C.; Shah, M.; Shu, X. O.; Simard, J.; Southey, M. C.; Stone, J.; Surowy, H.; Swerdlow, A. J.; Tamimi, R. M.; Tapper, W. J.; Taylor, J. A.; Terry, M. B.; Tollenaar, R A. E. M.; Troester, M. A.; Truong, T.; Untch, M.; Vachon, C. M.; Joseph, V.; Wappenschmidt, B.; Weinberg, C. R.; Wolk, A.; Yannoukakos, D.; Zheng, W.; Ziogas, A.; Dunning, A. M.; Pharoah, P. D. P.; Easton, D. F.; Milne, R. L.; Lynch, B. M.; on behalf of the Breast Cancer Association Consortium
Article Title: Physical activity, sedentary time and breast cancer risk: A Mendelian randomisation study
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;similar to 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 (similar to 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: instruments; genetic-variants; causal inference
Journal Title: British Journal of Sports Medicine
Volume: 56
Issue: 20
ISSN: 0306-3674
Publisher: BMJ Group  
Date Published: 2022-10-01
Start Page: 1157
End Page: 1170
Language: English
ACCESSION: WOS:000840803100001
DOI: 10.1136/bjsports-2021-105132
PROVIDER: wos
PUBMED: 36328784
PMCID: PMC9876601
Notes: Article -- Source: Wos
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  1. Kenneth Offit
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  2. Vijai Joseph
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