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

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 (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 27

Pages Range: 679-93

Journal Issue: 5

DOI: 10.1007/s10552-016-0741-6

Abstract

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.

Authors with CRIS profile

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Vanderbilt University United States (USA) (US) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Robert-Bosch-Krankenhaus Germany (DE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) The Institute of Cancer Research (ICR) United Kingdom (GB) National Centre for Scientific Research (NCSR) "Demokritos" Greece (GR) University of North Carolina at Chapel Hill United States (USA) (US) Cancer Council Victoria Australia (AU) National University of Singapore (NUS) Singapore (SG) The University of Melbourne Australia (AU) Cancer Prevention Institute of California (CPIC) United States (USA) (US) Mount Sinai Hospital (MSH) Canada (CA) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Fred Hutchinson Cancer Research Center Canada (CA) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Stanford University United States (USA) (US) Oulun Yliopisto / University of Oulo Finland (FI) Hospital Universitario La Paz Spain (ES) Harvard University United States (USA) (US) University of Cambridge United Kingdom (GB) Antoni van Leeuwenhoek Netherlands (NL) University of Copenhagen Denmark (DK) University of Chicago United States (USA) (US) Helsingin yliopisto / University of Helsinki Finland (FI) University of California Irvine United States (USA) (US) University of Southern California (USC) United States (USA) (US) Mayo Clinic United States (USA) (US) University of Sheffield United Kingdom (GB) Karolinska Institute Sweden (SE) Université Laval (UL) Canada (CA) National Cancer Institute (NCI) United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Copenhagen University Hospital Denmark (DK) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) University of Hawaii (U.H.) United States (USA) (US) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Ruprecht-Karls-Universität Heidelberg Germany (DE) The Alfred Hospital Australia (AU) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) Technische Universität München (TUM) Germany (DE) University of Warwick United Kingdom (GB) City of Hope Medical Center United States (USA) (US) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Columbia University United States (USA) (US) King’s College London United Kingdom (GB) Universitätsklinikum Köln Germany (DE) Ohio State University United States (USA) (US) University of Oxford United Kingdom (GB) University of Oslo Norway (NO) Universität Ulm Germany (DE) Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC)) Belgium (BE)

How to cite

APA:

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. https://dx.doi.org/10.1007/s10552-016-0741-6

MLA:

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.

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