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.
|Journal||British Journal of Sports Medicine|
|Publication status||Accepted/In press - 3 Jul 2022|
Research Beacons, Institutes and Platforms
- Manchester Cancer Research Centre
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Mitchell, N., Mecklenburgh, J., Rutter, E., Huuse, M., Finch, E., Chandler, M., Chang, Y., Zhao, Z., Shi, W., Bashir, Y., Ardo, B., Newton, A., Cox, D., Lloyd, C., Putuhena, H., Sarkar, A., Nnorom, S., Owolabi, O., Malah, M., Soutter, E., Dunlevy, E., Balila, A., Alhammami, S., Olobayo, O., Serié, C., Chenrai, P., Sharples, A., Le, A., Lamb, R., Harding, R., Gulmammadov, R., Calves, G., Bureau, D. & Muniz Pichel, L.