1. Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry
- Author
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Javier Benitez, Alicia Beeghly-Fadiel, Roger L. Milne, Graham G. Giles, Florentia Fostira, Senno Verhoef, Qin Wang, Simon S. Cross, Jenny Chang-Claude, Jacques Simard, Vessela N. Kristensen, Hoda Anton-Culver, Kathleen E. Malone, Veli-Matti Kosma, Pascal Guénel, Esther M. John, Stig E. Bojesen, Jan Lubinski, Patricia Harrington, Giske Ursin, Muhammad G. Kibriya, Artitaya Lophatananon, Mieke Kriege, Fergus J. Couch, Maria Kabisch, Judith S. Brand, Ute Hamann, Henrik Flyger, Susan L. Neuhausen, Elinor J. Sawyer, Mikael Hartman, Robert Luben, Thilo Dörk, Wanqing Wen, Hiltrud Brauch, Marilie D. Gammon, Xiao-Ou Shu, Ben Shan Zhang, Minouk J. Schoemaker, M. Pilar Zamora, Jirong Long, Rita K. Schmutzler, Natalia Bogdanova, Sofia Khan, Siranoush Manoukian, Anne Lise Børresen-Dale, Barbara Burwinkel, Regina M. Santella, Ian Tomlinson, Manjeet K. Bolla, Shan Wang-Gohrke, Nichola Johnson, Thérèse Truong, Rob B. van der Luijt, Amanda E. Toland, Carl Blomqvist, Catriona McLean, Georgia Chenevix-Trench, Anthony J. Swerdlow, Jingmei Li, Habibul Ahsan, David J. Hunter, Kristiina Aittomäki, Hui Zhao, Hui Miao, Wei Zheng, Olivia Fletcher, Alison M. Dunning, Marjanka K. Schmidt, Kenneth Muir, Per Hall, Farzana Jasmine, Eunjung Lee, Melissa C. Southey, Robert Winqvist, Janet E. Olson, Anna Jakubowska, Paul D.P. Pharoah, Martine Dumont, Dieter Flesch-Janys, Barbara Perkins, Douglas F. Easton, Christopher A. Haiman, Jonine D. Figueroa, Julia A. Knight, Kamila Czene, Loic Le Marchand, Katri Pylkäs, Angela Cox, Maartje J. Hooning, Kyriaki Michailidou, John L. Hopper, Qiuyin Cai, Volker Arndt, Heli Nevanlinna, Sara Lindström, Hanne Meijers-Heijboer, Sara Margolin, Zhiguo Zhao, Mitul Shah, Matthias W. Beckmann, Alfons Meindl, Martha J. Shrubsole, Paolo Peterlongo, Frederik Marmé, Peter Kraft, Irene L. Andrulis, Annika Lindblom, Diana Torres, Anja Rudolph, Arto Mannermaa, Graham Casey, Alice S. Whittemore, Hermann Brenner, Patrick Neven, Kelly-Anne Phillips, Peter A. Fasching, Montserrat Garcia-Closas, Human genetics, CCA - Cancer biology, Wang, Jean [0000-0002-9139-0627], Luben, Robert [0000-0002-5088-6343], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, and Medical Oncology
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,endocrine system diseases ,Epidemiology ,Genome-wide association study ,Type 2 diabetes ,Breast cancer ,0302 clinical medicine ,Risk Factors ,Ethnicity ,Odds Ratio ,GWAS ,Non-U.S. Gov't ,Research Support, Non-U.S. Gov't ,Middle Aged ,3. Good health ,030220 oncology & carcinogenesis ,Public Health and Health Services ,Female ,medicine.medical_specialty ,Oncology and Carcinogenesis ,European Continental Ancestry Group ,Non-P.H.S ,Ethnic Groups ,Breast Neoplasms ,Research Support ,Polymorphism, Single Nucleotide ,Article ,White People ,N.I.H ,03 medical and health sciences ,Research Support, N.I.H., Extramural ,SDG 3 - Good Health and Well-being ,Internal medicine ,Genetic susceptibility ,Journal Article ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,business.industry ,Case-control study ,Genetic Variation ,Extramural ,nutritional and metabolic diseases ,Cancer ,Odds ratio ,medicine.disease ,Obesity ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,U.S. Gov't ,business ,Research Support, U.S. Gov't, Non-P.H.S ,Demography - 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.\ud 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.\ud 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).\ud 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.
- Published
- 2016