Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation studyShow others and affiliations
2022 (English)In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 56, no 20, p. 1157-1170Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2022. Vol. 56, no 20, p. 1157-1170
Keywords [en]
Breast, Genetics, Physical activity, Sedentary Behaviour
National Category
Cancer and Oncology Public Health, Global Health and Social Medicine
Identifiers
URN: urn:nbn:se:uu:diva-489540DOI: 10.1136/bjsports-2021-105132ISI: 000840803100001PubMedID: 36328784OAI: oai:DiVA.org:uu-489540DiVA, id: diva2:1715173
Funder
Region StockholmKarolinska InstituteSwedish Cancer SocietyKing Gustaf V Jubilee FundBerth von Kantzows foundation2022-12-012022-12-012025-02-20Bibliographically approved