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

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    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.
    Investigators, A.
    Ahearn, T. U.
    Ambrosone, C. B.
    Andrulis, I. L.
    Anton-Culver, H.
    Arndt, V.
    Aronson, K. J.
    Augustinsson, A.
    Auvinen, P.
    Beane Freeman, L. E.
    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.
    García-Closas, M.
    García-Sáenz, J. A.
    Goldberg, M. S.
    Guénel, P.
    Gündert, M.
    Hahnen, E.
    Haiman, C. A.
    Häberle, L.
    Håkansson, N.
    Hall, P.
    Hamann, U.
    Hart, S. N.
    Harvie, M.
    Hillemanns, P.
    Hollestelle, A.
    Hooning, M. J.
    Hoppe, R.
    Hopper, J.
    Howell, Anthony
    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.
    Collaborators, N.
    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.
    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.
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    Affiliation
    Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
    Issue Date
    2022
    
    Metadata
    Show full item record
    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.
    Citation
    Dixon-Suen SC, Lewis SJ, Martin RM, English DR, Boyle T, Giles GG, et al. Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study. Br J Sports Med. 2022 Oct;56(20):1157-70. PubMed PMID: 36328784. Epub 2022/11/04. eng.
    Journal
    British Journal of Sports Medicine
    URI
    http://hdl.handle.net/10541/625754
    DOI
    10.1136/bjsports-2021-105132
    PubMed ID
    36328784
    Additional Links
    https://dx.doi.org/10.1136/bjsports-2021-105132
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1136/bjsports-2021-105132
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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