TY - JOUR
T1 - Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study
AU - Dixon-Suen, Suzanne C
AU - Lewis, Sarah J
AU - Martin, Richard M
AU - English, Dallas R
AU - Boyle, Terry
AU - Giles, Graham G
AU - Michailidou, Kyriaki
AU - Bolla, Manjeet K
AU - Wang, Qin
AU - Dennis, Joe
AU - Lush, Michael
AU - Investigators, Abctb
AU - Ahearn, Thomas U
AU - Ambrosone, Christine B
AU - Andrulis, Irene L
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Aronson, Kristan J
AU - Augustinsson, Annelie
AU - Auvinen, Päivi
AU - Beane Freeman, Laura E
AU - Becher, Heiko
AU - Beckmann, Matthias W
AU - Behrens, Sabine
AU - Bermisheva, Marina
AU - Blomqvist, Carl
AU - Bogdanova, Natalia V
AU - Bojesen, Stig E
AU - Bonanni, Bernardo
AU - Brenner, Hermann
AU - Brüning, Thomas
AU - Buys, Saundra S
AU - Camp, Nicola J
AU - Campa, Daniele
AU - Canzian, Federico
AU - Castelao, Jose E
AU - Cessna, Melissa H
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J
AU - Clarke, Christine L
AU - Conroy, Don M
AU - Couch, Fergus J
AU - Cox, Angela
AU - Cross, Simon S
AU - Czene, Kamila
AU - Daly, Mary B
AU - Devilee, Peter
AU - Hunter, David J
AU - Orr, Nick
AU - Scott, Christopher
AU - Breast Cancer Association Consortium
PY - 2022/9/6
Y1 - 2022/9/6
N2 - 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. 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 (n =5) or sedentary time (n =6), or accelerometer-measured (n =1) or self-reported (n =5) vigorous physical activity. 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). 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.
AB - 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. 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 (n =5) or sedentary time (n =6), or accelerometer-measured (n =1) or self-reported (n =5) vigorous physical activity. 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). 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.
KW - Polymorphism, Single Nucleotide
KW - Exercise
KW - Mendelian Randomization Analysis
KW - Physical activity
KW - Risk Factors
KW - Female
KW - Breast
KW - Sedentary Behavior
KW - Genetics
KW - Sedentary Behaviour
KW - Humans
KW - Breast Neoplasms - epidemiology - genetics
U2 - 10.1136/bjsports-2021-105132
DO - 10.1136/bjsports-2021-105132
M3 - Article
C2 - 36328784
VL - 56
SP - 1157
EP - 1170
JO - British Journal of Sports Medicine
JF - British Journal of Sports Medicine
IS - 20
ER -
