Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry.
Zhiguo Zhao,
Wanqing Wen,
Kyriaki Michailidou,
Manjeet K Bolla,
Qin Wang,
Ben Zhang,
Jirong Long,
Xiao-Ou Shu,
Marjanka K Schmidt,
Roger L Milne,
Montserrat García-Closas,
Jenny Chang-Claude,
Sara Lindstrom,
Stig E Bojesen,
Habibul Ahsan,
Kristiina Aittomäki,
Irene L Andrulis,
Hoda Anton-Culver,
Volker Arndt,
Matthias W Beckmann,
Alicia Beeghly-Fadiel,
Javier Benitez,
Carl Blomqvist,
Natalia V Bogdanova,
Anne-Lise Børresen-Dale,
Judith Brand,
Hiltrud Brauch,
Hermann Brenner,
Barbara Burwinkel,
Qiuyin Cai,
Graham Casey,
Georgia Chenevix-Trench,
Fergus J Couch,
Angela Cox,
Simon S Cross,
Kamila Czene,
Thilo Dörk,
Martine Dumont,
Peter A Fasching,
Jonine Figueroa,
Dieter Flesch-Janys,
Olivia Fletcher,
Henrik Flyger,
Florentia Fostira,
Marilie Gammon,
Graham G Giles,
Pascal Guénel,
Christopher A Haiman,
Ute Hamann,
Patricia Harrington,
Mikael Hartman,
Maartje J Hooning,
John L Hopper,
Anna Jakubowska,
Farzana Jasmine,
Esther M John,
Nichola Johnson,
Maria Kabisch,
Sofia Khan,
Muhammad Kibriya,
Julia A Knight,
Veli-Matti Kosma,
Mieke Kriege,
Vessela Kristensen,
Loic Le Marchand,
Eunjung Lee,
Jingmei Li,
Annika Lindblom,
Artitaya Lophatananon,
Robert Luben,
Jan Lubinski,
Kathleen E Malone,
Arto Mannermaa,
Siranoush Manoukian,
Sara Margolin,
Frederik Marme,
Catriona McLean,
Hanne Meijers-Heijboer,
Alfons Meindl,
Hui Miao,
Kenneth Muir,
Susan L Neuhausen,
Heli Nevanlinna,
Patrick Neven,
Janet E Olson,
Barbara Perkins,
Paolo Peterlongo,
Kelly-Anne Phillips,
Katri Pylkäs,
Anja Rudolph,
Regina Santella,
Elinor J Sawyer,
Rita K Schmutzler,
Minouk Schoemaker,
Mitul Shah,
Martha Shrubsole,
Melissa C Southey,
Anthony J Swerdlow,
Amanda E Toland,
Ian Tomlinson,
Diana Torres,
Thérèse Truong,
Giske Ursin,
Rob B Van Der Luijt,
Senno Verhoef,
Shan Wang-Gohrke,
Alice S Whittemore,
Robert Winqvist,
M Pilar Zamora,
Hui Zhao,
Alison M Dunning,
Jacques Simard,
Per Hall,
Peter Kraft,
Paul Pharoah,
David Hunter,
Douglas F Easton,
Wei Zheng
Abstract
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.
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.
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).
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.