Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry.
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Date
2016-05-01Author
Zhao, Z
Wen, W
Michailidou, K
Bolla, MK
Wang, Q
Zhang, B
Long, J
Shu, X-O
Schmidt, MK
Milne, RL
García-Closas, M
Chang-Claude, J
Lindstrom, S
Bojesen, SE
Ahsan, H
Aittomäki, K
Andrulis, IL
Anton-Culver, H
Arndt, V
Beckmann, MW
Beeghly-Fadiel, A
Benitez, J
Blomqvist, C
Bogdanova, NV
Børresen-Dale, A-L
Brand, J
Brauch, H
Brenner, H
Burwinkel, B
Cai, Q
Casey, G
Chenevix-Trench, G
Couch, FJ
Cox, A
Cross, SS
Czene, K
Dörk, T
Dumont, M
Fasching, PA
Figueroa, J
Flesch-Janys, D
Fletcher, O
Flyger, H
Fostira, F
Gammon, M
Giles, GG
Guénel, 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, V-M
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, K-A
Pylkäs, 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
Truong, T
Ursin, G
Van Der Luijt, RB
Verhoef, S
Wang-Gohrke, S
Whittemore, AS
Winqvist, R
Pilar Zamora, M
Zhao, H
Dunning, AM
Simard, J
Hall, P
Kraft, P
Pharoah, P
Hunter, D
Easton, DF
Zheng, W
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Breast Neoplasms
Diabetes Mellitus, Type 2
Genetic Predisposition to Disease
Odds Ratio
Risk Factors
Case-Control Studies
Polymorphism, Single Nucleotide
Middle Aged
European Continental Ancestry Group
Ethnic Groups
Female
Genetic Variation
Research team
Functional Genetic Epidemiology
Aetiological Epidemiology
Language
eng
Date accepted
2016-03-25
License start date
2016-05
Citation
Cancer causes & control : CCC, 2016, 27 (5), pp. 679 - 693
Publisher
SPRINGER