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

cam.depositDate2022-07-04
cam.issuedOnline2022-09-06
cam.orpheus.counter5
cam.orpheus.successMon Aug 29 08:26:37 BST 2022 - Embargo updated
dc.contributor.authorDixon-Suen, Suzanne C
dc.contributor.authorLewis, Sarah J
dc.contributor.authorMartin, Richard M
dc.contributor.authorEnglish, Dallas R
dc.contributor.authorBoyle, Terry
dc.contributor.authorGiles, Graham G
dc.contributor.authorMichailidou, Kyriaki
dc.contributor.authorBolla, Manjeet K
dc.contributor.authorWang, Qin
dc.contributor.authorDennis, Joe
dc.contributor.authorLush, Michael
dc.contributor.authorInvestigators, Abctb
dc.contributor.authorAhearn, Thomas U
dc.contributor.authorAmbrosone, Christine B
dc.contributor.authorAndrulis, Irene L
dc.contributor.authorAnton-Culver, Hoda
dc.contributor.authorArndt, Volker
dc.contributor.authorAronson, Kristan J
dc.contributor.authorAugustinsson, Annelie
dc.contributor.authorAuvinen, Päivi
dc.contributor.authorBeane Freeman, Laura E
dc.contributor.authorBecher, Heiko
dc.contributor.authorBeckmann, Matthias W
dc.contributor.authorBehrens, Sabine
dc.contributor.authorBermisheva, Marina
dc.contributor.authorBlomqvist, Carl
dc.contributor.authorBogdanova, Natalia V
dc.contributor.authorBojesen, Stig E
dc.contributor.authorBonanni, Bernardo
dc.contributor.authorBrenner, Hermann
dc.contributor.authorBrüning, Thomas
dc.contributor.authorBuys, Saundra S
dc.contributor.authorCamp, Nicola J
dc.contributor.authorCampa, Daniele
dc.contributor.authorCanzian, Federico
dc.contributor.authorCastelao, Jose E
dc.contributor.authorCessna, Melissa H
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorChanock, Stephen J
dc.contributor.authorClarke, Christine L
dc.contributor.authorConroy, Don M
dc.contributor.authorCouch, Fergus J
dc.contributor.authorCox, Angela
dc.contributor.authorCross, Simon S
dc.contributor.authorCzene, Kamila
dc.contributor.authorDaly, Mary B
dc.contributor.authorDevilee, Peter
dc.contributor.authorDörk, Thilo
dc.contributor.authorDwek, Miriam
dc.contributor.authorEccles, Diana M
dc.contributor.authorEliassen, A Heather
dc.contributor.authorEngel, Christoph
dc.contributor.authorEriksson, Mikael
dc.contributor.authorEvans, D Gareth
dc.contributor.authorFasching, Peter A
dc.contributor.authorFletcher, Olivia
dc.contributor.authorFlyger, Henrik
dc.contributor.authorFritschi, Lin
dc.contributor.authorGabrielson, Marike
dc.contributor.authorGago-Dominguez, Manuela
dc.contributor.authorGarcía-Closas, Montserrat
dc.contributor.authorGarcía-Sáenz, José A
dc.contributor.authorGoldberg, Mark S
dc.contributor.authorGuénel, Pascal
dc.contributor.authorGündert, Melanie
dc.contributor.authorHahnen, Eric
dc.contributor.authorHaiman, Christopher A
dc.contributor.authorHäberle, Lothar
dc.contributor.authorHåkansson, Niclas
dc.contributor.authorHall, Per
dc.contributor.authorHamann, Ute
dc.contributor.authorHart, Steven N
dc.contributor.authorHarvie, Michelle
dc.contributor.authorHillemanns, Peter
dc.contributor.authorHollestelle, Antoinette
dc.contributor.authorHooning, Maartje J
dc.contributor.authorHoppe, Reiner
dc.contributor.authorHopper, John
dc.contributor.authorHowell, Anthony
dc.contributor.authorHunter, David J
dc.contributor.authorJakubowska, Anna
dc.contributor.authorJanni, Wolfgang
dc.contributor.authorJohn, Esther M
dc.contributor.authorJung, Audrey
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorKeeman, Renske
dc.contributor.authorKitahara, Cari M
dc.contributor.authorKoutros, Stella
dc.contributor.authorKraft, Peter
dc.contributor.authorKristensen, Vessela N
dc.contributor.authorKubelka-Sabit, Katerina
dc.contributor.authorKurian, Allison W
dc.contributor.authorLacey, James V
dc.contributor.authorLambrechts, Diether
dc.contributor.authorLe Marchand, Loic
dc.contributor.authorLindblom, Annika
dc.contributor.authorLoibl, Sibylle
dc.contributor.authorLubiński, Jan
dc.contributor.authorMannermaa, Arto
dc.contributor.authorManoochehri, Mehdi
dc.contributor.authorMargolin, Sara
dc.contributor.authorMartinez, Maria Elena
dc.contributor.authorMavroudis, Dimitrios
dc.contributor.authorMenon, Usha
dc.contributor.authorMulligan, Anna Marie
dc.contributor.authorMurphy, Rachel A
dc.contributor.authorCollaborators, Nbcs
dc.contributor.authorNevanlinna, Heli
dc.contributor.authorNevelsteen, Ines
dc.contributor.authorNewman, William G
dc.contributor.authorOffit, Kenneth
dc.contributor.authorOlshan, Andrew F
dc.contributor.authorOlsson, Håkan
dc.contributor.authorOrr, Nick
dc.contributor.authorPatel, Alpa
dc.contributor.authorPeto, Julian
dc.contributor.authorPlaseska-Karanfilska, Dijana
dc.contributor.authorPresneau, Nadege
dc.contributor.authorRack, Brigitte
dc.contributor.authorRadice, Paolo
dc.contributor.authorRees-Punia, Erika
dc.contributor.authorRennert, Gad
dc.contributor.authorRennert, Hedy S
dc.contributor.authorRomero, Atocha
dc.contributor.authorSaloustros, Emmanouil
dc.contributor.authorSandler, Dale P
dc.contributor.authorSchmidt, Marjanka K
dc.contributor.authorSchmutzler, Rita K
dc.contributor.authorSchwentner, Lukas
dc.contributor.authorScott, Christopher
dc.contributor.authorShah, Mitul
dc.contributor.authorShu, Xiao-Ou
dc.contributor.authorSimard, Jacques
dc.contributor.authorSouthey, Melissa C
dc.contributor.authorStone, Jennifer
dc.contributor.authorSurowy, Harald
dc.contributor.authorSwerdlow, Anthony J
dc.contributor.authorTamimi, Rulla M
dc.contributor.authorTapper, William J
dc.contributor.authorTaylor, Jack A
dc.contributor.authorTerry, Mary Beth
dc.contributor.authorTollenaar, Rob AEM
dc.contributor.authorTroester, Melissa A
dc.contributor.authorTruong, Thérèse
dc.contributor.authorUntch, Michael
dc.contributor.authorVachon, Celine M
dc.contributor.authorJoseph, Vijai
dc.contributor.authorWappenschmidt, Barbara
dc.contributor.authorWeinberg, Clarice R
dc.contributor.authorWolk, Alicja
dc.contributor.authorYannoukakos, Drakoulis
dc.contributor.authorZheng, Wei
dc.contributor.authorZiogas, Argyrios
dc.contributor.authorDunning, Alison M
dc.contributor.authorPharoah, Paul DP
dc.contributor.authorEaston, Douglas F
dc.contributor.authorMilne, Roger L
dc.contributor.authorLynch, Brigid M
dc.contributor.authorBreast Cancer Association Consortium
dc.contributor.orcidDixon-Suen, Suzanne C [0000-0003-3714-8386]
dc.contributor.orcidBoyle, Terry [0000-0001-6741-330X]
dc.contributor.orcidRomero, Atocha [0000-0002-1634-7397]
dc.contributor.orcidLynch, Brigid M [0000-0001-8060-547X]
dc.date.accessioned2022-07-04T23:30:35Z
dc.date.available2022-07-04T23:30:35Z
dc.date.issued2022-10
dc.date.updated2022-07-04T07:27:28Z
dc.description.abstractOBJECTIVES: 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.
dc.identifier.doi10.17863/CAM.86162
dc.identifier.eissn1473-0480
dc.identifier.issn0306-3674
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338752
dc.language.isoeng
dc.publisherBMJ
dc.publisher.departmentDepartment of Public Health And Primary Care, Cancer Genetic Epidemiology
dc.publisher.urlhttp://dx.doi.org/10.1136/bjsports-2021-105132
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectBreast
dc.subjectGenetics
dc.subjectPhysical activity
dc.subjectSedentary Behaviour
dc.subjectFemale
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectExercise
dc.subjectMendelian Randomization Analysis
dc.subjectPolymorphism, Single Nucleotide
dc.subjectRisk Factors
dc.subjectSedentary Behavior
dc.titlePhysical activity, sedentary time and breast cancer risk: a Mendelian randomisation study.
dc.typeArticle
dcterms.dateAccepted2022-06-29
prism.publicationNameBr J Sports Med
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idWellcome Trust (203477/Z/16/Z)
pubs.funder-project-idMedical Research Council (G1000143)
pubs.funder-project-idNational Cancer Institute (U19CA148537)
pubs.funder-project-idNational Cancer Institute (R01CA128978)
pubs.funder-project-idNational Cancer Institute (U19CA148065)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (634935)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (633784)
pubs.funder-project-idCancer Research UK (A10710)
pubs.funder-project-idCancer Research UK (A16563)
pubs.funder-project-idCancer Research UK (A12014)
pubs.funder-project-idCancer Research UK (A10118)
pubs.funder-project-idNational Cancer Institute (P30CA023100)
pubs.funder-project-idMedical Research Council (G0401527)
pubs.funder-project-idMedical Research Council (MR/N003284/1)
pubs.funder-project-idEuropean Commission (223175)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1136/bjsports-2021-105132

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