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, 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 AL, 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 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, 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
Cancer Causes Control 27 679-93 05/01/2016


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.

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