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

• Published in: Cancer causes & control 2016-05, Vol.27 (5), p.679-693
• Main Authors: Zhao, Zhiguo, Wen, Wanqing, Bolla, Manjeet K., Zhang, Ben, Shu, Xiao-Ou, Schmidt, Marjanka K., Milne, Roger L., García-Closas, Montserrat, Chang-Claude, Jenny, Bojesen, Stig E., Ahsan, Habibul, Anton-Culver, Hoda, Arndt, Volker, Beeghly-Fadiel, Alicia, Benitez, Javier, Blomqvist, Carl, Bogdanova, Natalia V., Børresen-Dale, Anne-Lise, Brand, Judith, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Cai, Qiuyin, Casey, Graham, Chenevix-Trench, Georgia, Couch, Fergus J., Cross, Simon S., Czene, Kamila, Dörk, Thilo, Dumont, Martine, Fasching, Peter A., Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Gammon, Marilie, Giles, Graham G., Guénel, Pascal, Haiman, Christopher A., Hamann, Ute, Harrington, Patricia, Hartman, Mikael, Hopper, John L., Jakubowska, Anna, Jasmine, Farzana, John, Esther M., Johnson, Nichola, Kabisch, Maria, Khan, Sofia, Kibriya, Muhammad, Knight, Julia A., Kosma, Veli-Matti, Kriege, Mieke, Kristensen, Vessela, Lee, Eunjung, Li, Jingmei, Lophatananon, Artitaya, Luben, Robert, Lubinski, Jan, Malone, Kathleen E., Mannermaa, Arto, Margolin, Sara, Marme, Frederik, McLean, Catriona, Meijers-Heijboer, Hanne, Meindl, Alfons, Miao, Hui, Muir, Kenneth, Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Olson, Janet E., Perkins, Barbara, Phillips, Kelly-Anne, Pylkäs, Katri, Rudolph, Anja, Santella, Regina, Schmutzler, Rita K., Shah, Mitul, Southey, Melissa C., Swerdlow, Anthony J., Toland, Amanda E., Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Ursin, Giske, Van Der Luijt, Rob B., Verhoef, Senno, Wang-Gohrke, Shan, Whittemore, Alice S., Winqvist, Robert, Zhao, Hui, Dunning, Alison M., Simard, Jacques, Hall, Per, Kraft, Peter, Pharoah, Paul, Hunter, David, Easton, Douglas F., Zheng, Wei
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - genetics; Cancer Research; Case-Control Studies; Diabetes; Diabetes Mellitus, Type 2 - genetics; Epidemiology; Ethnicity; Female; Genetic Predisposition to Disease; Genetic Variation; Hematology; Humans; Life Sciences; Medical research; Medicin och hälsovetenskap; Middle Aged; Odds Ratio; Oncology; Original Paper; ORIGINAL PAPERS; Polymorphism, Single Nucleotide; Public Health; Risk Factors; White People - genetics; Womens health
• ISSN: 0957-5243; 1573-7225; 1573-7225
• DOI: 10.1007/s10552-016-0741-6

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