Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
Dixon-Suen, S.C. ; Augustinsson, A. LU ; Olsson, H. LU
and Lynch, B.M.
(2022)
In British journal of sports medicine
56(20).
p.1157-1170
- 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... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/33b1be06-6bf7-43ac-a73c-1357fab4e5bf
- author
- Dixon-Suen, S.C.
; Augustinsson, A.
LU
; Olsson, H.
LU
and Lynch, B.M.
- author collaboration
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British journal of sports medicine
- volume
- 56
- issue
- 20
- pages
- 1157 - 1170
- publisher
- BMJ Publishing Group
- external identifiers
-
- scopus:85137660444
- pmid:36328784
- ISSN
- 0306-3674
- DOI
- 10.1136/bjsports-2021-105132
- language
- English
- LU publication?
- yes
- id
- 33b1be06-6bf7-43ac-a73c-1357fab4e5bf
- date added to LUP
- 2023-01-12 16:09:20
- date last changed
- 2023-01-13 03:00:10
@article{33b1be06-6bf7-43ac-a73c-1357fab4e5bf,
abstract = {{Objectives <br/>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.<br/><br/>Methods <br/>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.<br/><br/>Results <br/>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).<br/><br/>Conclusion <br/>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.}},
author = {{Dixon-Suen, S.C. and Augustinsson, A. and Olsson, H. and Lynch, B.M.}},
issn = {{0306-3674}},
language = {{eng}},
number = {{20}},
pages = {{1157--1170}},
publisher = {{BMJ Publishing Group}},
series = {{British journal of sports medicine}},
title = {{Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study}},
url = {{http://dx.doi.org/10.1136/bjsports-2021-105132}},
doi = {{10.1136/bjsports-2021-105132}},
volume = {{56}},
year = {{2022}},
}