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

Guo Q, Burgess S, Turman C, Bolla MK, Wang Q, Lush M, Abraham J, Aittomaki K, Andrulis IL, Apicella C, Arndt V, Barrdahl M, Benitez J, Berg CD, Blomqvist C, Bojesen SE, Bonanni B, Brand JS, Brenner H, Broeks A, Burwinkel B, Caldas C, Campa D, Canzian F, Chang-Claude J, Chanock SJ, Chin SF, Couch FJ, Cox A, Cross SS, Cybulski C, Czene K, Darabi H, Devilee P, Diver WR, Dunning AM, Earl HM, Eccles DM, Ekici AB, Eriksson M, Evans DG, Fasching P, Figueroa J, Flesch-Janys D, Flyger H, Gapstur SM, Gaudet MM, Giles GG, Glendon G, Grip M, Gronwald J, Häberle L, Haiman CA, Hall P, Hamann U, Hankinson S, Hartikainen JM, Hein A, Hiller L, Hogervorst FB, Holleczek B, Hooning MJ, Hoover RN, Humphreys K, Hunter DJ, Husing A, Jakubowska A, Jukkola-Vuorinen A, Kaaks R, Kabisch M, Kataja V, Knight JA, Koppert LB, Kosma VM, Kristensen VN, Lambrechts D, Le Marchand L, Li J, Lindblom A, Lindstrom S, Lissowska J, Lubinski J, Machiela MJ, Mannermaa A, Manoukian S, Margolin S, Marme F, Martens JWM, Mclean C, Menendez P, Milne RL, Mulligan AM, Muranen TA, Nevanlinna H, Neven P, Nielsen SF, Nordestgaard BG, Olson JE, Perez JIA, Peterlongo P, Phillips KA, Poole CJ, Pylkas K, Radice P, Rahman N, Rudiger T, Rudolph A, Sawyer EJ, Schumacher F, Seibold P, Seynaeve C, Shah M, Smeets A, Southey MC, Tollenaar RAEM, Tomlinson I, Tsimiklis H, Ulmer HU, Vachon C, Van Den Ouweland AMW, Van'T Veer LJ, Wildiers H, Willett W, Winqvist R, Zamora MP, Chenevix-Trench G, Dork T, Easton DF, Garcia-Closas M, Kraft P, Hopper JL, Zheng W, Schmidt MK, Pharoah PDP (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 46

Pages Range: 1814-1822

Journal Issue: 6

DOI: 10.1093/ije/dyx131

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.

Authors with CRIS profile

Involved external institutions

University of Cambridge United Kingdom (GB) Harvard University United States (USA) (US) Helsingin yliopisto / University of Helsinki Finland (FI) Mount Sinai Hospital (MSH) Canada (CA) The University of Melbourne Australia (AU) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) National Cancer Institute (NCI) United States (USA) (US) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Karolinska Institute Sweden (SE) Antoni van Leeuwenhoek Netherlands (NL) Ruprecht-Karls-Universität Heidelberg Germany (DE) University of Pisa / Università di Pisa (UniPi) Italy (IT) Mayo Clinic United States (USA) (US) University of Sheffield United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Leiden University Netherlands (NL) American Cancer Society United States (USA) (US) University of Southampton United Kingdom (GB) University of Manchester United Kingdom (GB) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) University of Copenhagen Denmark (DK) Oulun Yliopisto / University of Oulo Finland (FI) University of Southern California (USC) United States (USA) (US) University of Massachusetts Amherst (UMass) United States (USA) (US) University of Eastern Finland Finland (FI) University of Warwick United Kingdom (GB) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) Erasmus University Medical Center (MC) Netherlands (NL) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University of Hawaii (U.H.) United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Istituto di ricovero e cura a carattere scientifico (IRCCS) Italy (IT) The Alfred Hospital Australia (AU) University of Toronto Canada (CA) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Copenhagen University Hospital Denmark (DK) Hospital Monte Naranco Spain (ES) IFOM - FIRC Institute of Molecular Oncology Italy (IT) The Institute of Cancer Research (ICR) United Kingdom (GB) Städtisches Klinikum Karlsruhe Germany (DE) University of Oxford United Kingdom (GB) King’s College London United Kingdom (GB) Case Western Reserve University United States (USA) (US) Klinikum Mittelbaden Baden-Baden Balg Germany (DE) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) Hospital Universitario La Paz Spain (ES) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Vanderbilt University United States (USA) (US)

How to cite

APA:

Guo, Q., Burgess, S., Turman, C., Bolla, M.K., Wang, Q., Lush, M.,... Pharoah, P.D.P. (2017). Body mass index and breast cancer survival: a Mendelian randomization analysis. International Journal of Epidemiology, 46(6), 1814-1822. https://dx.doi.org/10.1093/ije/dyx131

MLA:

Guo, Qi, et al. "Body mass index and breast cancer survival: a Mendelian randomization analysis." International Journal of Epidemiology 46.6 (2017): 1814-1822.

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