Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

Journal article

Publication Details

Author(s): Zhao Z, Wen W, Michailidou K, Bolla MK, Wang Q, Zhang B, Long J, Shu XO, Schmidt MK, Milne RL, Garcia-Closas M, Chang-Claude J, Lindstrom S, Bojesen SE, Ahsan H, Aittomaki K, Andrulis IL, Anton-Culver H, Arndt V, Beckmann M, Beeghly-Fadiel A, Benitez J, Blomqvist C, Bogdanova NV, Borresen-Dale AL, Brand J, Brauch H, Brenner H, Burwinkel B, Cai Q, Casey G, Chenevix-Trench G, Couch FJ, Cox A, Cross SS, Czene K, Doerk T, Dumont M, Fasching P, Figueroa J, Flesch-Janys D, Fletcher O, Flyger H, Fostira F, Gammon M, Giles GG, Guenel P, Haiman CA, Hamann U, Harrington P, Hartman M, Hooning MJ, Hopper JL, Jakubowska A, Jasmine F, John EM, Johnson N, Kabisch M, Khan S, Kibriya M, Knight JA, Kosma VM, Kriege M, Kristensen V, Le Marchand L, Lee E, Li J, Lindblom A, Lophatananon A, Luben R, Lubinski J, Malone KE, Mannermaa A, Manoukian S, Margolin S, Marme F, Mclean C, Meijers-Heijboer H, Meindl A, Miao H, Muir K, Neuhausen SL, Nevanlinna H, Neven P, Olson JE, Perkins B, Peterlongo P, Phillips KA, Pylkas K, Rudolph A, Santella R, Sawyer EJ, Schmutzler RK, Schoemaker M, Shah M, Shrubsole M, Southey MC, Swerdlow AJ, Toland AE, Tomlinson I, Torres D, Therese Truong , Ursin G, Van Der Luijt RB, Verhoef S, Wang-Gohrke S, Whittemore AS, Winqvist R, Zamora MP, Zhao H, Dunning AM, Simard J, Hall P, Kraft P, Pharoah P, Hunter D, Easton DF, Zheng W
Journal: Cancer Causes & Control
Publication year: 2016
Volume: 27
Journal issue: 5
Pages range: 679-93
ISSN: 0957-5243


PURPOSE: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors.
METHODS: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies.
RESULTS: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92-0.95, p = 4.13E-13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02-1.06, p = 1.26E-05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95-0.99, p = 8.05E-04).
CONCLUSIONS: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.

FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe

External institutions with authors

Antoni van Leeuwenhoek
Cancer Council Victoria
Cancer Prevention Institute of California (CPIC)
Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC))
City of Hope Medical Center
Columbia University
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
Fondazione IRCCS: Istituto Nazionale dei Tumori
Fred Hutchinson Cancer Research Center
Harvard University
Helsingin yliopisto / University of Helsinki
Hospital Universitario La Paz
IFOM - FIRC Institute of Molecular Oncology
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
King’s College London
Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri
Mayo Clinic
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National Centre for Scientific Research (NCSR) "Demokritos"
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
National University of Singapore (NUS)
Ohio State University
Oslo University Hospital / Oslo Universitetssykehus
Oulun Yliopisto / University of Oulo
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Ruprecht-Karls-Universität Heidelberg
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Stanford University
Technische Universität München (TUM)
The Alfred Hospital
The Institute of Cancer Research (ICR)
The University of Melbourne
Universitätsklinikum Hamburg-Eppendorf (UKE)
Universitätsklinikum Köln
Universität Ulm
Université Laval (UL)
University Medical Centre Utrecht (UMC Utrecht)
University of California Irvine
University of Cambridge
University of Chicago
University of Copenhagen
University of Hawaii (U.H.)
University of North Carolina at Chapel Hill
University of Oslo
University of Oxford
University of Sheffield
University of Southern California (USC)
University of Warwick
Vanderbilt University
Vrije Universiteit Amsterdam (VU) / University Amsterdam

How to cite

Zhao, Z., Wen, W., Michailidou, K., Bolla, M.K., Wang, Q., Zhang, B.,... Zheng, W. (2016). Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry. Cancer Causes & Control, 27(5), 679-93.

Zhao, Zhiguo, et al. "Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry." Cancer Causes & Control 27.5 (2016): 679-93.


Last updated on 2019-21-07 at 07:54