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Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study.

Authors :
Dixon-Suen SC
Lewis SJ
Martin RM
English DR
Boyle T
Giles GG
Michailidou K
Bolla MK
Wang Q
Dennis J
Lush M
Investigators A
Ahearn TU
Ambrosone CB
Andrulis IL
Anton-Culver H
Arndt V
Aronson KJ
Augustinsson A
Auvinen P
Beane Freeman LE
Becher H
Beckmann MW
Behrens S
Bermisheva M
Blomqvist C
Bogdanova NV
Bojesen SE
Bonanni B
Brenner H
Brüning T
Buys SS
Camp NJ
Campa D
Canzian F
Castelao JE
Cessna MH
Chang-Claude J
Chanock SJ
Clarke CL
Conroy DM
Couch FJ
Cox A
Cross SS
Czene K
Daly MB
Devilee P
Dörk T
Dwek M
Eccles DM
Eliassen AH
Engel C
Eriksson M
Evans DG
Fasching PA
Fletcher O
Flyger H
Fritschi L
Gabrielson M
Gago-Dominguez M
García-Closas M
García-Sáenz JA
Goldberg MS
Guénel P
Gündert M
Hahnen E
Haiman CA
Häberle L
Håkansson N
Hall P
Hamann U
Hart SN
Harvie M
Hillemanns P
Hollestelle A
Hooning MJ
Hoppe R
Hopper J
Howell A
Hunter DJ
Jakubowska A
Janni W
John EM
Jung A
Kaaks R
Keeman R
Kitahara CM
Koutros S
Kraft P
Kristensen VN
Kubelka-Sabit K
Kurian AW
Lacey JV
Lambrechts D
Le Marchand L
Lindblom A
Loibl S
Lubiński J
Mannermaa A
Manoochehri M
Margolin S
Martinez ME
Mavroudis D
Menon U
Mulligan AM
Murphy RA
Collaborators N
Nevanlinna H
Nevelsteen I
Newman WG
Offit K
Olshan AF
Olsson H
Orr N
Patel A
Peto J
Plaseska-Karanfilska D
Presneau N
Rack B
Radice P
Rees-Punia E
Rennert G
Rennert HS
Romero A
Saloustros E
Sandler DP
Schmidt MK
Schmutzler RK
Schwentner L
Scott C
Shah M
Shu XO
Simard J
Southey MC
Stone J
Surowy H
Swerdlow AJ
Tamimi RM
Tapper WJ
Taylor JA
Terry MB
Tollenaar RAEM
Troester MA
Truong T
Untch M
Vachon CM
Joseph V
Wappenschmidt B
Weinberg CR
Wolk A
Yannoukakos D
Zheng W
Ziogas A
Dunning AM
Pharoah PDP
Easton DF
Milne RL
Lynch BM
Source :
British journal of sports medicine [Br J Sports Med] 2022 Oct; Vol. 56 (20), pp. 1157-1170. Date of Electronic Publication: 2022 Sep 06.
Publication Year :
2022

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.<br />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 (n <subscript>snps</subscript> =5) or sedentary time (n <subscript>snps</subscript> =6), or accelerometer-measured (n <subscript>snps</subscript> =1) or self-reported (n <subscript>snps</subscript> =5) vigorous physical activity.<br />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).<br />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.<br />Competing Interests: Competing interests: MWB conducts research funded by Amgen, Novartis and Pfizer. PAF conducts research funded by Amgen, Novartis and Pfizer. He received honoraria from Roche, Novartis and Pfizer. AWK declares research funding to her institution from Myriad Genetics for an unrelated project (funding dates 2017-2019). SL declares grants and honoraria paid to her institution from Amgen, Novartis, Pfizer, Roche, and, outside the submitted work, grants and/or honoraria paid to her institution from AbbVie, Celgene, Seattle Genetics, PrIME/Medscape, Daiichi-Sankyo, Lilly, Samsung, BMS, Puma, Immunomedics, AstraZeneca, Pierre Fabre, Merck, GlaxoSmithKlein, EirGenix, and Bayer, and personal fees from Chugai; SL also has a patent EP14153692.0 pending. UM declares stock ownership in Abcodia Ltd. RAM has been a consultant for Pharmavite. No other authors have conflicts to declare.<br /> (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Details

Language :
English
ISSN :
1473-0480
Volume :
56
Issue :
20
Database :
MEDLINE
Journal :
British journal of sports medicine
Publication Type :
Academic Journal
Accession number :
36328784
Full Text :
https://doi.org/10.1136/bjsports-2021-105132