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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Divi Mol Pathol, Amsterdam, Netherlands.
Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England;Cambridge Expt Canc Med Ctr, Cambridge, England;Univ Cambridge NHS Fdn Hosp, NIHR Cambridge Biomed Res Ctr, Cambridge, England;Univ Cambridge NHS Fdn Hosp, Cambridge Breast Unit, Cambridge, England.
Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Toronto, ON, Canada;Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
Univ Calif Irvine, Genet Epidemiol Res Inst, Dept Epidemiol, Irvine, CA USA.
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2020 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 11, no 1, article id 312Article in journal (Refereed) Published
Abstract [en]

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2020. Vol. 11, no 1, article id 312
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Medical Genetics
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URN: urn:nbn:se:uu:diva-407461DOI: 10.1038/s41467-019-14100-6ISI: 000511912200002PubMedID: 31949161OAI: oai:DiVA.org:uu-407461DiVA, id: diva2:1417161
Funder
EU, Horizon 2020, 634935EU, Horizon 2020, 633784EU, FP7, Seventh Framework Programme, 223175EU, FP7, Seventh Framework Programme, HEALTH-F2-2009-223175EU, FP7, Seventh Framework Programme, 223175 (HEALTH-F2-2009-223175)Swedish Cancer SocietySwedish Research CouncilSwedish Cancer SocietySwedish Research Council, VR 2017-00644EU, European Research CouncilAvailable from: 2020-03-26 Created: 2020-03-26 Last updated: 2020-03-26Bibliographically approved

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Arndt, VolkerBlomqvist, CarlEarl, Helena M.Howell, AnthonyOlsson, HakanRamachandran, DhanyaRomero, AtochaWolk, Alicja
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