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Qi Guo, Stephen Burgess, Constance Turman, Manjeet K Bolla, Qin Wang, Michael Lush, Jean Abraham, Kristiina Aittomäki, Irene L Andrulis, Carmel Apicella, Volker Arndt, Myrto Barrdahl, Javier Benitez, Christine D Berg, Carl Blomqvist, Stig E Bojesen, Bernardo Bonanni, Judith S Brand, Hermann Brenner, Annegien Broeks, Barbara Burwinkel, Carlos Caldas, Daniele Campa, Federico Canzian, Jenny Chang-Claude, Stephen J Chanock, Suet-Feung Chin, Fergus J Couch, Angela Cox, Simon S Cross, Cezary Cybulski, Kamila Czene, Hatef Darabi, Peter Devilee, W Ryan Diver, Alison M Dunning, Helena M Earl, Diana M Eccles, Arif B Ekici, Mikael Eriksson, D Gareth Evans, Peter A Fasching, Jonine Figueroa, Dieter Flesch-Janys, Henrik Flyger, Susan M Gapstur, Mia M Gaudet, Graham G Giles, Gord Glendon, Mervi Grip, Jacek Gronwald, Lothar Haeberle, Christopher A Haiman, Per Hall, Ute Hamann, Susan Hankinson, Jaana M Hartikainen, Alexander Hein, Louise Hiller, Frans B Hogervorst, Bernd Holleczek, Maartje J Hooning, Robert N Hoover, Keith Humphreys, David J Hunter, Anika Hüsing, Anna Jakubowska, Arja Jukkola-Vuorinen, Rudolf Kaaks, Maria Kabisch, Vesa Kataja, Julia A Knight, Linetta B Koppert, Veli-Matti Kosma, Vessela N Kristensen, Diether Lambrechts, Loic Le Marchand, Jingmei Li, Annika Lindblom, Sara Lindström, Jolanta Lissowska, Jan Lubinski, Mitchell J Machiela, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Federik Marme, John WM Martens, Catriona McLean, Primitiva Menéndez, Roger L Milne, Anna Marie Mulligan, Taru A Muranen, Heli Nevanlinna, Patrick Neven, Sune F Nielsen, Børge G Nordestgaard, Janet E Olson, Jose IA Perez, Paolo Peterlongo, Kelly-Anne Phillips, Christopher J Poole, Katri Pylkäs, Paolo Radice, Nazneen Rahman, Thomas Rüdiger, Anja Rudolph, Elinor J Sawyer, Fredrick Schumacher, Petra Seibold, Caroline Seynaeve, Mitul Shah, Ann Smeets, Melissa C Southey, Rob A E M Tollenaar, Ian Tomlinson, Helen Tsimiklis, Hans-Ulrich Ulmer, Celine Vachon, Ans MW van den Ouweland, Laura J Van’t Veer, Hans Wildiers, Walter Willett, Robert Winqvist, M Pilar Zamora, Georgia Chenevix-Trench, Thilo Dörk, Douglas F Easton, Montserrat García-Closas, Peter Kraft, John L Hopper, Wei Zheng, Marjanka K Schmidt, Paul DP Pharoah, Body mass index and breast cancer survival: a Mendelian randomization analysis, International Journal of Epidemiology, Volume 46, Issue 6, December 2017, Pages 1814–1822, https://doi.org/10.1093/ije/dyx131

Body mass index and breast cancer survival : a Mendelian randomization analysis

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Author: Guo, Qi1; Burgess, Stephen1,2; Turman, Constance3;
Bolla, Manjeet K.4; Wang, Qin4; Lush, Michael4; Abraham, Jean5,6; Aittomaki, Kristiina7; Andrulis, Irene L.8,9; Apicella, Carmel10; Arndt, Volker11; Barrdahl, Myrto12; Benitez, Javier13,14; Berg, Christine D.15; Blomqvist, Carl16; Bojesen, Stig E.; Bonanni, Bernardo17; Brand, Judith S.18; Brenner, Hermann11,19,20,21; Broeks, Annegien22; Burwinkel, Barbara23,24; Caldas, Carlos6,25,26,27; Campa, Daniele28; Canzian, Federico29; Chang-Claude, Jenny12,30; Chanock, Stephen J.15; Chin, Suet-Feung27; Couch, Fergus J.31; Cox, Angela32; Cross, Simon S.33; Cybulski, Cezary34; Czene, Kamila18; Darabi, Hatef18; Devilee, Peter35,36; Diver, W. Ryan37; Dunning, Alison M.5; Earl, Helena M.6,25,26; Eccles, Diana M.38; Ekici, Arif B.39; Eriksson, Mikael18; Evans, D. Gareth40; Fasching, Peter A.41,42; Figueroa, Jonine15,43; Flesch-Janys, Dieter44,45; Flyger, Henrik46; Gapstur, Susan M.37; Gaudet, Mia M.37; Giles, Graham G.10,47; Glendon, Gord8; Grip, Mervi48; Gronwald, Jacek34; Haeberle, Lothar41; Haiman, Christopher A.49; Hall, Per18; Hamann, Ute50; Hankinson, Susan51; Hartikainen, Jaana M.52,53,54; Hein, Alexander41; Hiller, Louise55; Hogervorst, Frans B.56; Holleczek, Bernd57; Hooning, Maartje J.58; Hoover, Robert N.15; Humphreys, Keith18; Hunter, David J.3,59; Husing, Anika12; Jakubowska, Anna34; Jukkola-Vuorinen, Arja60; Kaaks, Rudolf12; Kabisch, Maria50; Kataja, Vesa52,61; Knight, Julia A.62,63; Koppert, Linetta B.64; Kosma, Veli-Matti52,53,54; Kristensen, Vessela N.65,66,67; Lambrechts, Diether68,69; Le Marchand, Loic70; Li, Jingmei18; Lindblom, Annika71; Lindstrom, Sara3,72; Lissowska, Jolanta73; Lubinski, Jan34; Machiela, Mitchell J.15; Mannermaa, Arto52,53,54; Manoukian, Siranoush74; Margolin, Sara75; Marme, Federik23,76; Martens, John W. M.58; McLean, Catriona77; Menendez, Primitiva78; Milne, Roger L.10,47; Mulligan, Anna Marie79,80; Muranen, Taru A.81; Nevanlinna, Heli81; Neven, Patrick82; Nielsen, Sune F.83,84,85; Nordestgaard, Borge G.; Olson, Janet E.86; Perez, Jose I. A.87; Peterlongo, Paolo88; Phillips, Kelly-Anne10,89,90,91; Poole, Christopher J.55; Pylkas, Katri92,93; Radice, Paolo94; Rahman, Nazneen95; Rudiger, Thomas96; Rudolph, Anja12; Sawyer, Elinor J.97; Schumacher, Fredrick98; Seibold, Petra12; Seynaeve, Caroline58; Shah, Mitul5; Smeets, Ann82; Southey, Melissa C.99; Tollenaar, Rob A. E. M.100; Tomlinson, Ian101,102; Tsimiklis, Helen99; Ulmer, Hans-Ulrich103; Vachon, Celine86; van den Ouweland, Ans M. W.104; Van't Veer, Laura J.22; Wildiers, Hans82; Willett, Walter105; Winqvist, Robert92,93; Zamora, M. Pilar106; Chenevix-Trench, Georgia107; Dork, Thilo108; Easton, Douglas F.4,5; Garcia-Closas, Montserrat15; Kraft, Peter3,59; Hopper, John L.10; Zheng, Wei109; Schmidt, Marjanka K.22,110; Pharoah, Paul D. P.4,5
Organizations: 1Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England.
2Univ Cambridge, MRC, Biostat Unit, Cambridge, England.
3Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA.
4Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
5Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
6Cambridge Expt Canc Med Ctr, Cambridge, England.
7Univ Helsinki, Helsinki Univ Hosp, Dept Clin Genet, Helsinki, Finland.
8Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
9Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
10Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
11German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
12German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
13Spanish Natl Canc Res Ctr, Human Canc Genet Program, Madrid, Spain.
14Ctr Invest Red Enfermedades Raras CIBERER, Valencia, Spain.
15Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA.
16Univ Helsinki, Helsinki Univ Hosp, Dept Oncol, Helsinki, Finland.
17Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
18Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
19German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
20Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
21German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
22Antoni van Leeuwenhoek Hosp, Div Mol Pathol, Netherlands Canc Inst, Amsterdam, Netherlands.
23Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
24German Canc Res Ctr, Mol Epidemiol Grp, C080, Heidelberg, Germany.
25Univ Cambridge, Cambridge Breast Unit, NHS Fdn Hosp, Cambridge, England.
26Univ Cambridge, NIHR Cambridge Biomed Res Ctr, NHS Fdn Hosp, Cambridge, England.
27Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Breast Canc Funct Genom Lab, Cambridge, England.
28Univ Pisa, Dept Biol, Pisa, Italy.
29German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
30Univ Canc Ctr Hamburg, Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.
31Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
32Univ Sheffield, Acad Unit Mol Oncol, Dept Oncol & Metab, Sheffield, S Yorkshire, England.
33Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England.
34Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
35Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
36Leiden Univ, Dept Human Genet, Med Ctr, Leiden, Netherlands.
37Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
38Univ Southampton, Fac Med, Canc Sci Acad Unit, Southampton, Hants, England.
39Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Inst Human Genet, Comprehens Canc Ctr Erlangen EMN, Erlangen, Germany.
40Univ Manchester, Genom Med, Manchester Acad Hlth Sci Ctr, Cent Manchester Fdn Trust,St Marys Hosp, Manchester, Lancs, England.
41Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen EMN, Erlangen, Germany.
42Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
43Univ Edinburgh, Med Sch, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
44Univ Med Ctr Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
45Univ Med Ctr Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany.
46Univ Copenhagen, Herlev & Gentofte Hosp, Dept Breast Surg, Herlev, Denmark.
47Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia.
48Univ Oulu, Oulu Univ Hosp, Dept Surg, Oulu, Finland.
49Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
50German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
51Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA.
52Univ Eastern Finland, Translat Canc Res Area, Kuopio, Finland.
53Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
54Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, Kuopio, Finland.
55Univ Warwick, Warwick Clin Trials Unit, Coventry, W Midlands, England.
56Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
57Saarland Canc Registry, Saarbrucken, Germany.
58Erasmus MC Canc Inst, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
59Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
60Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland.
61Jyvaskyla Cent Hosp, Cent Finland Hlth Care Dist, Jyvaskyla, Finland.
62Mt Sinai Hosp, Prosserman Ctr Hlth Res, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
63Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada.
64Erasmus MC Canc Inst, Dept Surg Oncol, Family Canc Clin, Rotterdam, Netherlands.
65Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway.
66Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway.
67Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway.
68VIB Ctr Canc Biol, Leuven, Belgium.
69Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium.
70Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
71Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
72Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
73M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Oncol Inst, Warsaw, Poland.
74Fondazione IRCCS Ist Ricovero Cura & Carattere Sc, INT, Dept Med Oncol & Hematol, Unit Med Genet, Milan, Italy.
75Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
76Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
77Alfred Hosp, Anat Pathol, Melbourne, Vic, Australia.
78Hosp Monte Naranco, Serv Anat Patol, Oviedo, Spain.
79Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
80Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
81Univ Helsinki, Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
82Univ Hosp Leuven, Leuven Multidisciplinary Breast Ctr, Dept Oncol, Leuven Canc Inst, Leuven, Belgium.
83Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Herlev, Denmark.
84Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark.
85Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
86Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
87Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain.
88FIRC Italian Fdn Canc Res, IFOM, Inst Mol Oncol, Milan, Italy.
89Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Australia.
90Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Australia.
91Univ Melbourne, Dept Med, St Vincents Hosp, Fitzroy, Vic, Australia.
92Univ Oulu, Bioctr Oulu, Canc & Translat Med Res Unit, Lab Canc Genet & Tumor Biol, Oulu, Finland.
93Northern Finland Lab Ctr Oulu, Lab Canc Genet & Tumor Biol, Oulu, Finland.
94Fdn IRCCS Ist Ricovero & Cura Carattere Sci, INT, Dept Res, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy.
95Inst Canc Res, Div Genet & Epidemiol, London, England.
96Staedt Klinikum Karlsruhe, Inst Pathol, Karlsruhe, Germany.
97Kings Coll London, Guys Hosp, Res Oncol, London, England.
98Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
99Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
100Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands.
101Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
102Univ Oxford, Oxford NIHR Biomed Res Ctr, Oxford, England.
103Frauenklin Stadtklin Baden Baden, Baden, Switzerland.
104Erasmus Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands.
105Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
106Hosp Univ La Paz, Serv Oncol Med, Madrid, Spain.
107QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia.
108Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
109Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
110Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202103258467
Language: English
Published: Oxford University Press, 2017
Publish Date: 2021-03-25
Description:

Abstract

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.

Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.

Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01–1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89–1.13, P = 0.95).

Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.

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Series: International journal of epidemiology
ISSN: 0300-5771
ISSN-E: 1464-3685
ISSN-L: 0300-5771
Volume: 46
Issue: 6
Pages: 1814 - 1822
DOI: 10.1093/ije/dyx131
OADOI: https://oadoi.org/10.1093/ije/dyx131
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
3141 Health care science
Subjects:
Mendelian randomization
body mass index
breast cancer survival
epidemiology
genetics
Article
Copyright information: © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cite
  https://creativecommons.org/licenses/by/4.0/