Physical activity, sedentary time and breast cancer risk: A Mendelian randomization study
Authors
Journal Title
British Journal of Sports Medicine
ISSN
0306-3674
Publisher
BMJ Publishing Group
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Pharoah, P. Physical activity, sedentary time and breast cancer risk: A Mendelian randomization study. British Journal of Sports Medicine https://doi.org/10.17863/CAM.86162
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.
Sponsorship
Cancer Research Uk (None)
Wellcome Trust (203477/Z/16/Z)
Embargo Lift Date
2025-07-04
Identifiers
This record's DOI: https://doi.org/10.17863/CAM.86162
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338752
Rights
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/
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