Physical activity, sedentary time and breast cancer risk: A Mendelian randomization study

Details

• Alternative Title:
  Br J Sports Med
• Personal Author:
  Dixon-Suen, Suzanne C. ; Lewis, Sarah J. ; Martin, Richard M. ; English, Dallas R. ; Boyle, Terry ; Giles, Graham G. ; Michailidou, Kyriaki ; Bolla, Manjeet K. ; Wang, Qin ; Dennis, Joe ; Lush, Michael ; Ahearn, Thomas U. ; Ambrosone, Christine B. ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Arndt, Volker ; Aronson, Kristan J. ; Augustinsson, Annelie ; Auvinen, Päivi ; Beane Freeman, Laura E. ; Becher, Heiko ; Beckmann, Matthias W. ; Behrens, Sabine ; Bermisheva, Marina ; Blomqvist, Carl ; Bogdanova, Natalia V. ; Bojesen, Stig E. ; Bonanni, Bernardo ; Brenner, Hermann ; Brüning, Thomas ; Buys, Saundra S. ; Camp, Nicola J. ; Campa, Daniele ; Canzian, Federico ; Castelao, Jose E. ; Cessna, Melissa H. ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Clarke, Christine L. ; Conroy, Don M. ; Couch, Fergus J. ; Cox, Angela ; Cross, Simon S. ; Czene, Kamila ; Daly, Mary B. ; Devilee, Peter ; Dörk, Thilo ; Dwek, Miriam ; Eccles, Diana M. ; Eliassen, A. Heather ; Engel, Christoph ; Eriksson, Mikael ; Evans, D. Gareth ; Fasching, Peter A. ; Fletcher, Olivia ; Flyger, Henrik ; Fritschi, Lin ; Gabrielson, Marike ; Gago-Dominguez, Manuela ; García-Closas, Montserrat ; García-Sáenz, José A. ; Goldberg, Mark S. ; Guénel, Pascal ; Gündert, Melanie ; Hahnen, Eric ; Haiman, Christopher A. ; Häberle, Lothar ; Håkansson, Niclas ; Hall, Per ; Hamann, Ute ; Hart, Steven N. ; Harvie, Michelle ; Hillemanns, Peter ; Hollestelle, Antoinette ; Hooning, Maartje J. ; Hoppe, Reiner ; Hopper, John L. ; Howell, Anthony ; Hunter, David J. ; Jakubowska, Anna ; Janni, Wolfgang ; John, Esther M. ; Jung, Audrey ; Kaaks, Rudolf ; Keeman, Renske ; Kitahara, Cari M. ; Koutros, Stella ; Kraft, Peter ; Kristensen, Vessela N. ; Kubelka-Sabit, Katerina ; Kurian, Allison W. ; Lacey, James V. ; Lambrechts, Diether ; Le Marchand, Loic ; Lindblom, Annika ; Loibl, Sibylle ; Lubiński, Jan ; Mannermaa, Arto ; Manoochehri, Mehdi ; Margolin, Sara ; Martinez, Maria Elena ; Mavroudis, Dimitrios ; Menon, Usha ; Mulligan, Anna Marie ; Murphy, Rachel A. ; Nevanlinna, Heli ; Nevelsteen, Ines ; Newman, William G. ; Offit, Kenneth ; Olshan, Andrew F. ; Olsson, Håkan ; Orr, Nick ; Patel, Alpa V. ; Peto, Julian ; Plaseska-Karanfilska, Dijana ; Presneau, Nadege ; Rack, Brigitte ; Radice, Paolo ; Rees-Punia, Erika ; Rennert, Gad ; Rennert, Hedy S. ; Romero, Atocha ; Saloustros, Emmanouil ; Sandler, Dale P. ; Schmidt, Marjanka K. ; Schmutzler, Rita K. ; Schwentner, Lukas ; Scott, Christopher ; Shah, Mitul ; Shu, Xiao-Ou ; Simard, Jacques ; Southey, Melissa C. ; Stone, Jennifer ; Surowy, Harald ; Swerdlow, Anthony J. ; Tamimi, Rulla M. ; Tapper, William J. ; Taylor, Jack A. ; Terry, Mary Beth ; Tollenaar, Rob A.E.M. ; Troester, Melissa A. ; Truong, Thérèse ; Untch, Michael ; Vachon, Celine M. ; Joseph, Vijai ; Wappenschmidt, Barbara ; Weinberg, Clarice R. ; Wolk, Alicja ; Yannoukakos, Drakoulis ; Zheng, Wei ; Ziogas, Argyrios ; Dunning, Alison M. ; Pharoah, Paul D.P. ; Easton, Douglas F. ; Milne, Roger L. ; Lynch, Brigid M.
• Corporate Authors:
  ABCTB Investigators ; NBCS Collaborators
• Description:
  Objectives:
  
  Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomization (MR) assesses causality by simulating randomized 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 risk, overall (OR=0.59; 95%CI 0.42–0.83 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 0.45–0.87, ≥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 1.07–2.92 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.
  
  
• Subjects:
  Breast Neoplasms Exercise Female Humans Mendelian Randomization Analysis Polymorphism, Single Nucleotide Risk Factors Sedentary Behavior
• Keywords:
  Breast Cancer Causal Inference Mendelian Randomization Physical Activity Sedentary Time
• Source:
  Br J Sports Med. 56(20):1157-1170
• Pubmed ID:
  36328784
• Pubmed Central ID:
  PMC9876601
• Document Type:
  Journal Article
• Funding:
  R01 CA176785/CA/NCI NIH HHSUnited States/ ; NU58DP006344/DP/NCCDPHP CDC HHSUnited States/ ; 29186/CRUK_/Cancer Research UKUnited Kingdom/ ; HHSN261201800015I/CA/NCI NIH HHSUnited States/ ; MR/N003284/1/MRC_/Medical Research CouncilUnited Kingdom/ ; 29019/CRUK_/Cancer Research UKUnited Kingdom/ ; HHSN261201800015C/CA/NCI NIH HHSUnited States/ ; R01 CA163353/CA/NCI NIH HHSUnited States/ ; UM1 CA164917/CA/NCI NIH HHSUnited States/ ; U01 CA199277/CA/NCI NIH HHSUnited States/ ; U01 CA179715/CA/NCI NIH HHSUnited States/ ; MC_PC_17228/MRC_/Medical Research CouncilUnited Kingdom/ ; R01 CA128931/CA/NCI NIH HHSUnited States/ ; HHSN261201800032C/CA/NCI NIH HHSUnited States/ ; U54 CA156733/CA/NCI NIH HHSUnited States/ ; MC_UU_00011/4/MRC_/Medical Research CouncilUnited Kingdom/ ; HHSN261201800009C/CA/NCI NIH HHSUnited States/ ; Z01 CP010119/ImNIH/Intramural NIH HHSUnited States/ ; UM1 CA164973/CA/NCI NIH HHSUnited States/ ; P01 CA087969/CA/NCI NIH HHSUnited States/ ; UM1 CA164920/CA/NCI NIH HHSUnited States/ ; R01 CA097396/CA/NCI NIH HHSUnited States/ ; UM1 CA176726/CA/NCI NIH HHSUnited States/ ; Z01 ES049030/ImNIH/Intramural NIH HHSUnited States/ ; R01 CA058860/CA/NCI NIH HHSUnited States/ ; HHSN261201800016C/CA/NCI NIH HHSUnited States/ ; MC_UU_00011/6/MRC_/Medical Research CouncilUnited Kingdom/ ; K07 CA092044/CA/NCI NIH HHSUnited States/ ; MC_UU_00011/1/MRC_/Medical Research CouncilUnited Kingdom/ ; P50 CA058223/CA/NCI NIH HHSUnited States/ ; R01 CA100374/CA/NCI NIH HHSUnited States/ ; P30 CA008748/CA/NCI NIH HHSUnited States/ ; R01 CA128978/CA/NCI NIH HHSUnited States/ ; U19 CA148537/CA/NCI NIH HHSUnited States/ ; G0401527/MRC_/Medical Research CouncilUnited Kingdom/ ; R01 CA116167/CA/NCI NIH HHSUnited States/ ; R01 CA177150/CA/NCI NIH HHSUnited States/ ; P50 CA116201/CA/NCI NIH HHSUnited States/ ; Z99 CA999999/ImNIH/Intramural NIH HHSUnited States/ ; R01 CA063464/CA/NCI NIH HHSUnited States/ ; HHSN261201800016I/CA/NCI NIH HHSUnited States/ ; UM1 CA186107/CA/NCI NIH HHSUnited States/ ; G1000143/MRC_/Medical Research CouncilUnited Kingdom/ ; 16561/CRUK_/Cancer Research UKUnited Kingdom/ ; P30 CA023100/CA/NCI NIH HHSUnited States/ ; U01 CA063464/CA/NCI NIH HHSUnited States/ ; R01 CA077398/CA/NCI NIH HHSUnited States/ ; R01 CA054281/CA/NCI NIH HHSUnited States/ ; R01 CA132839/CA/NCI NIH HHSUnited States/ ; P30 CA068485/CA/NCI NIH HHSUnited States/ ; U01 CA058860/CA/NCI NIH HHSUnited States/ ; U01 CA164920/CA/NCI NIH HHSUnited States/ ; R35 CA253187/CA/NCI NIH HHSUnited States/ ; 14136/CRUK_/Cancer Research UKUnited Kingdom/ ; U19 CA148112/CA/NCI NIH HHSUnited States/ ; HHSN261201800032I/CA/NCI NIH HHSUnited States/ ; U01 CA098758/CA/NCI NIH HHSUnited States/ ; Z01 ES044005/ImNIH/Intramural NIH HHSUnited States/ ; U19 CA148065/CA/NCI NIH HHSUnited States/ ; WT_/Wellcome TrustUnited Kingdom/ ; MC_UU_00011/3/MRC_/Medical Research CouncilUnited Kingdom/ ; P30 CA033572/CA/NCI NIH HHSUnited States/ ; Z01 ES049033/ImNIH/Intramural NIH HHSUnited States/ ; R01 CA192393/CA/NCI NIH HHSUnited States/ ; P30 CA071789/CA/NCI NIH HHSUnited States/ ; R37 CA054281/CA/NCI NIH HHSUnited States/ ; U01 CA164973/CA/NCI NIH HHSUnited States/ ; R01 CA140286/CA/NCI NIH HHSUnited States/ ; MR/M012190/1/MRC_/Medical Research CouncilUnited Kingdom/ ; P30 CA042014/CA/NCI NIH HHSUnited States/ ; MC_QA137853/MRC_/Medical Research CouncilUnited Kingdom/ ; HHSN261201800009I/CA/NCI NIH HHSUnited States/
• Volume:
  56
• Issue:
  20
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:c7b162b6084f26b3c2aed2da5d69c0ed000202a3e48a3490b1909b367c92c91c448a7f170550399c581668c61f728643b012178c735ce241fae4880ba70c690b
• Download URL:
  https://stacks.cdc.gov/view/cdc/162088/cdc_162088_DS1.pdf
• File Type:
  [PDF - 458.21 KB ]