Physical activity, sedentary time and breast cancer risk: A Mendelian randomization study

D. Gareth Evans, Anthony Howell, William G. Newman, et al.

Research output: Contribution to journal › Article › peer-review

Abstract

Objectives: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomization (MR) assesses causality by simulating randomized 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 risk, overall (OR=0.59; 95%CI 0.42-0.83 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 0.45-0.87, ≥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 1.07-2.92 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 languageEnglish
JournalBritish Journal of Sports Medicine
Publication statusAccepted/In press - 3 Jul 2022

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-being

    Embargoed Document

  • BCAC_MR_PhysActSitting_risk_final_BJSM_SecondRev_CLEAN

    Accepted author manuscript, 285 KB

    Embargo ends: 1/01/32

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  • Geophysics

    Mitchell, N. (PI), Mecklenburgh, J. (PI), Rutter, E. (PI), Huuse, M. (PI), Finch, E. (PI), Chandler, M. (PI), Chang, Y.-C. (PGR student), Zhao, Z. (PGR student), Shi, W. (PGR student), Bashir, Y. (PGR student), Ardo, B. (PGR student), Newton, A. (PGR student), Cox, D. (PGR student), Lloyd, C. (PGR student), Putuhena, H. (PGR student), Sarkar, A. (PGR student), Nnorom, S. (PGR student), Owolabi, O. (PGR student), Malah, M. (PGR student), Soutter, E. (PGR student), Dunlevy, E. (PGR student), Balila, A. (PGR student), Alhammami, S. (PGR student), Olobayo, O. (PGR student), Serié, C. (PGR student), Chenrai, P. (PGR student), Sharples, A. (PGR student), Le, A. (PGR student), Lamb, R. (PGR student), Harding, R. (PGR student), Gulmammadov, R. (PGR student), Calves, G. (CoI), Bureau, D. (CoI) & Muniz Pichel, L. (PGR student)

    Project: Research

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