Browse by author
Lookup NU author(s): Dr Fiona Douglas
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
There have been few definitive examples of gene-gene interactions in humans. Through mutational analyses in 7325 individuals, we report four interactions (defined as departures from a multiplicative model) between mutations in the breast cancer susceptibility genes ATM and CHEK2 with BRCA1 and BRCA2 (case-only interaction between ATM and BRCA1/BRCA2 combined, P = 5.9 x 10(-4); ATM and BRCA1, P = 0.01; ATM and BRCA2, P = 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 x 10(-4); CHEK2 and BRCA1, P = 0.01; CHEK2 and BRCA2, P = 0.01). The interactions are such that the resultant risk of breast cancer is lower than the multiplicative product of the constituent risks, and plausibly reflect the functional relationships of the encoded proteins in DNA repair. These findings have important implications for models of disease predisposition and clinical translation.
Author(s): Turnbull C, Seal S, Renwick A, Warren-Perry M, Hughes D, Elliott A, Pernet D, Peock S, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L, Ahmed M, Eccles D, Evans DG, Donnelly P, Easton DF, Stratton MR, Rahman N, Breast Canc Susceptibility, EMBRACE
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2012
Volume: 21
Issue: 4
Pages: 958-962
Print publication date: 09/11/2011
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/hmg/ddr525
DOI: 10.1093/hmg/ddr525
Altmetrics provided by Altmetric