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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Height and body mass index as Modifiers of breast cancer risk in BRCA1/2 mutation carriers: A Mendelian randomization study
Journal of the National Cancer Institute, Volume 111, No. 4, Year 2019
Notification
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Description
Background: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. Methods: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants.We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. Results: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P=1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P=.47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P=.007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P=.02). BMI was primarily associated with premenopausal breast cancer. Conclusion: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management. © The Author(s) 2018. Published by Oxford University Press. All rights reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC6449171/bin/djy132_supp.zip
Authors & Co-Authors
Qian, Frank
United States, Chicago
The University of Chicago
Wang, Shengfeng
United States, Chicago
The University of Chicago
China, Beijing
Peking University Health Science Center
Mitchell, Jonathan A.
United States, Philadelphia
The Children's Hospital of Philadelphia
McGuffog, Lesley
United Kingdom, Cambridge
University of Cambridge
Barrowdale, Daniel
United Kingdom, Cambridge
University of Cambridge
Leslie, Goska
United Kingdom, Cambridge
University of Cambridge
Oosterwijk, Jan C.
Netherlands, Groningen
Rijksuniversiteit Groningen
Chung, Wendy Kay
United States, New York
Columbia University
Evans, D. Gareth R.
United Kingdom, Manchester
Health Innovation Manchester
Engel, Christoph
Germany, Leipzig
Universität Leipzig
Kast, Karin
Germany, Dresden
Technische Universität Dresden
Aalfs, Cora M.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Adank, Muriel A.
Netherlands, Amsterdam
The Netherlands Cancer Institute
Adlard, Julian W.
United Kingdom, Leeds
Chapel Allerton Hospital
Agnarsson, Bjarni Agnar
Hungary, Budapest
Országos Onkológiai Intézet Budapest
Iceland, Reykjavik
Haskoli Islands
Aittomäki, Kristiina A.U.
Finland, Helsinki
Helsingin Yliopisto
Alducci, Elisa
Italy, Padua
Istituto Oncologico Veneto Iov - Irccs
Andrulis, Irene L.
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Canada, Toronto
University of Toronto
Arun, Banu K.
United States, Houston
The University of Texas Md Anderson Cancer Center
Ausems, Margreet G.E.M.
Netherlands, Utrecht
University Medical Center Utrecht
Azzollini, Jacopo
Italy, Milan
Fondazione Irccs Istituto Nazionale Dei Tumori, Milan
Barouk-Simonet, Emmanuelle
France, Bordeaux
Institut Bergonie
Barwell, Julian G.
United Kingdom, Wakefield
Nhs England
Belotti, Muriel
France, Paris
Institut Curie
Benit́ez, Javier J.
Spain, Madrid
Centro Nacional de Investigaciones Oncológicas
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Berger, Andreas
Austria, Vienna
Medizinische Universität Wien
Borg, Åke
Sweden, Lund
Lunds Universitet
Bradbury, Angela R.
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Brunet, Joan Maria
Spain, Madrid
Centro de Investigación Biomédica en Red de Cáncer
Buys, Saundra S.
United States, Salt Lake City
The University of Utah
Caldés, Trinidad
Spain, Madrid
Centro de Investigación Biomédica en Red de Cáncer
Caligo, Maria Adelaide
Italy, Pisa
Università Di Pisa
Campbell, I. G. G.
Australia, Melbourne
Peter Maccallum Cancer Centre
Caputo, S. M.
France, Paris
Institut Curie
Chiquette, Jocelyne
Canada, Quebec
Chu de Québec-université Laval
Claes, Kathleen B.M.
Belgium, Ghent
Universiteit Gent
Margriet Collée, J.
Netherlands, Rotterdam
Erasmus Mc
Couch, Fergus J.
United States, Rochester
Mayo Clinic
Coupier, Isabelle
France, Montpellier
Hopital Arnaud de Villeneuve
Daly, Mary B.
United States, Philadelphia
Fox Chase Cancer Center
Davidson, Rosemarie H.
United Kingdom, Glasgow
Queen Elizabeth University Hospital, Glasgow
Díez, Orland
Spain, Barcelona
Vall D‘hebron Institut de Oncologia
Domchek, Susan M.
France, Paris
Institut Curie
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Donaldson, Alan
United Kingdom, Bristol
St. Michael's Hospital
Dorfling, Cecilia M.
South Africa, Pretoria
University of Pretoria
Eeles, Ros A.
United Kingdom, London
The Institute of Cancer Research
Feliubadaló, Lidia
Spain, Madrid
Centro de Investigación Biomédica en Red de Cáncer
Forétova, Lenka
Czech Republic, Brno
Masaryk Memorial Cancer Institute
Fowler, Jeffrey Mc Cabe
United States, Columbus
The Ohio State University
Friedman, Eitan A.
Israel, Tel Hashomer Tel Aviv
Chaim Sheba Medical Center Israel
Israel, Tel Aviv-yafo
Tel Aviv University
Frost, Debra
United Kingdom, Cambridge
University of Cambridge
Ganz, Patricia A.
United States, Los Angeles
University of California, Los Angeles
Garber, Judy Ellen
United States, Boston
Dana-farber Cancer Institute
García-Barberán, Vanesa
Spain, Madrid
Centro de Investigación Biomédica en Red de Cáncer
Glendon, Gord
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Godwin, Andrew K.
United States, Kansas City
University of Kansas Medical Center
Gómez-Garćia, Encarna B.
Netherlands, Maastricht
Maastricht Universitair Medisch Centrum+
Gronwald, Jacek
Poland, Szczecin
Pomeranian Medical University in Szczecin
Hahnen, Eric T.
Germany, Koln
Uniklinik Köln
Hamann, Ute
Germany, Heidelberg
German Cancer Research Center
Henderson, Alex
United Kingdom, Newcastle
University of Newcastle Upon Tyne, Faculty of Medical Sciences
Hendricks, Carolyn B.
United States, Duarte
City of Hope National Med Center
Hopper, John Llewelyn
Australia, Melbourne
University of Melbourne
Hulick, Peter J.
United States, Evanston
Northshore University Healthsystem
United States, Chicago
Pritzker School of Medicine
Imyanitov, Evgeny N.
Russian Federation, Saint Petersburg
N.n. Petrov Research Institute of Oncology of the Ussr Ministry of Health
Isaacs, Claudine J.
United States, Washington, D.c.
Georgetown University
Izatt, Louise
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Izquierdo, Ángel J.
Spain, Madrid
Centro de Investigación Biomédica en Red de Cáncer
Jakubowska, Anna
Poland, Szczecin
Pomeranian Medical University in Szczecin
Kaczmarek, Katarzyna
Poland, Szczecin
Pomeranian Medical University in Szczecin
Kang, Eunyoung
South Korea, Seongnam
Seoul National University Bundang Hospital
Karlan, Beth Y.
United States, Los Angeles
Cedars-sinai Medical Center
Kets, Carolien Marleen
Netherlands, Nijmegen
Radboud University Medical Center
Kim, Sungwon
South Korea, Seoul
The Catholic University of Korea Seoul St. Mary's Hospital
Kim, Zisun
South Korea, Seoul
Soonchunhyang University, College of Medicine
Kwong, Ava
Hong Kong, Hong Kong
Hong Kong Hereditary Breast Cancer Family Registry
Hong Kong, Hong Kong
The University of Hong Kong
China, Hong Kong
Hong Kong Sanatorium and Hospital
Laitman, Yael
Israel, Tel Hashomer Tel Aviv
Chaim Sheba Medical Center Israel
Lasset, Christine
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Lee, Min-hyuk
South Korea, Seoul
Soonchunhyang University, College of Medicine
Lee, Jongwon
South Korea, Seoul
Asan Medical Center
Lee, Jihyoun
South Korea, Seoul
Soonchunhyang University, College of Medicine
Lester, Jenny
Poland, Szczecin
Pomeranian Medical University in Szczecin
Lesueur, Fabienne El Khoury
France, Paris
Institut Curie
France, Paris
Cancer et Génome : Bioinformatique, Biostatistiques et Épidémiologie Des Systèmes Complexes
France, Paris
Université Psl
France, Paris
Mines Paris - Psl
Loud, Jennifer T.
United States, Rockville
National Cancer Institute Nci
Lubiński, Jan
United States, Los Angeles
Cedars-sinai Medical Center
Mebirouk, Noura
France, Paris
Institut Curie
France, Paris
Cancer et Génome : Bioinformatique, Biostatistiques et Épidémiologie Des Systèmes Complexes
France, Paris
Université Psl
France, Paris
Mines Paris - Psl
Meijers-Heijboer, Hanne E.J.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Meindl, Alfons
Germany, Munich
Technische Universität München
Miller, Austin
United States, Buffalo
Roswell Park Cancer Institute
Montagna, Marco
Italy, Padua
Istituto Oncologico Veneto Iov - Irccs
Mooij, Thea M.
Netherlands, Amsterdam
The Netherlands Cancer Institute
Morrison, Patrick J.
United Kingdom, Belfast
Queen's University Belfast
Mouret-Fourme, Emmanuelle
France, Paris
Institut Curie
Nathanson, Katherine L.
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Floris, Giuseppe L.
United States, Duarte
City of Hope National Med Center
Nevanlinna, Heli A.
Finland, Helsinki
Helsingin Yliopisto
Niederacher, Dieter
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Nielsen, Finn Cilius
Denmark, Copenhagen
Copenhagen University Hospital
Nussbaum, Robert Luke
United States, San Francisco
University of California, San Francisco
Offit, Kenneth
United States, New York
Memorial Sloan-kettering Cancer Center
Oláh, Edith
Hungary, Budapest
Országos Onkológiai Intézet Budapest
Ong, Kairen
United Kingdom, Birmingham
Birmingham Women’s and Children’s Nhs Foundation Trust
Ottini, Laura
Italy, Rome
Sapienza Università Di Roma
Park, Suekyung
South Korea, Seoul
Seoul National University
Peterlongo, Paolo
Italy, Milan
Fondazione Ifom Istituto Firc Di Oncologia Molecolare
Pfeiler, Georg
Austria, Vienna
Medizinische Universität Wien
Phelan, Catherine M.
United States, Tampa
Moffitt Cancer Center
Poppe, Bruce
Belgium, Ghent
Universiteit Gent
Pradhan, Nisha
United States, New York
Memorial Sloan-kettering Cancer Center
Radice, Paolo
Italy, Milan
Fondazione Irccs Istituto Nazionale Dei Tumori, Milan
Ramus, Susan J.
Australia, Sydney
Unsw Sydney
Australia, Sydney
The Kinghorn Cancer Centre
Rantala, Johanna
Sweden, Stockholm
Karolinska Institutet
Robson, Mark E.
United States, New York
Memorial Sloan-kettering Cancer Center
Rodríguez, Gustavo C.
United States, Chicago
The University of Chicago
Schmutzler, Rita Katharina
Germany, Koln
Uniklinik Köln
Shah, Payal Deepak
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Simard, Jacques
Canada, Quebec
Université Laval
Singer, Christian Fridolin
Austria, Vienna
Medizinische Universität Wien
Sokolowska, Joanna
France, Nancy
Chu de Nancy
Stoppa-Lyonnet, Dominique
France, Paris
Institut Curie
France, Paris
Université Paris Cité
Sutter, Christian
Germany, Heidelberg
Universitätsklinikum Heidelberg
Teixeira, Manuel Rodrigues
Portugal, Porto
Instituto Português de Oncologia do Porto fg
Portugal, Porto
Universidade do Porto
Teo, Soo Hwang
Malaysia, Kuala Lumpur
University of Malaya Medical Centre
Thomassen, Mads Christella L.G.D.
Denmark, Odense
Odense Universitetshospital
Tischkowitz, Marc D.
Canada, Montreal
Université Mcgill
United Kingdom, Cambridge
Addenbrooke's Hospital
Toland, Amanda Ewart
United States, Columbus
The Ohio State University
Tucker, Kathy M.
Australia, Kensington
Unsw Medicine
Australia, Sydney
Prince of Wales Hospital
Tung, Nadine M.
United States, Boston
Beth Israel Deaconess Medical Center
van Asperen, Christi J.
Netherlands, Leiden
Universiteit Leiden
van Rensburg, Elizabeth J.
South Africa, Pretoria
University of Pretoria
Wang-Gohrke, Shan
Germany, Ulm
Universität Ulm
Wappenschmidt, Barbara
Germany, Koln
Uniklinik Köln
Weitzel, Jeffrey Nelson
United States, Duarte
City of Hope National Med Center
Yannoukakos, Drakoulis
Greece, Athens
National Centre for Scientific Research Demokritos
Rebbeck, Timothy Richard
United States, Boston
Harvard T.h. Chan School of Public Health
United States, Boston
Dana-farber Cancer Institute
Greene, Mark H.
United States, Rockville
National Cancer Institute Nci
Rookus, Matti A.
Netherlands, Amsterdam
The Netherlands Cancer Institute
d'Adamo, Adamo P.
United Kingdom, Cambridge
University of Cambridge
Chenevix-Trench, Georgia
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Antoniou, Antonis C.
United Kingdom, Cambridge
University of Cambridge
Goldgar, David E.
United States, Salt Lake City
The University of Utah
Olopade, Olufunmilayo Ibironke
United States, Chicago
The University of Chicago
Huo, Dezheng
United States, Chicago
The University of Chicago
Statistics
Citations: 25
Authors: 143
Affiliations: 111
Identifiers
Doi:
10.1093/jnci/djy132
ISSN:
00278874
Research Areas
Cancer
Genetics And Genomics
Study Design
Randomised Control Trial