TY - JOUR
T1 - A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
AU - Escala Garcia, Maria
AU - Abraham, Jean
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Ashworth, Alan
AU - Auer, Paul L.
AU - Auvinen, Päivi
AU - Beckmann, Matthias W.
AU - Beesley, Jonathan
AU - Wessels, Lodewyk F.A.
AU - More Authors, null
PY - 2020
Y1 - 2020
N2 - 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 ~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.
AB - 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 ~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.
UR - http://www.scopus.com/inward/record.url?scp=85077940819&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-14100-6
DO - 10.1038/s41467-019-14100-6
M3 - Article
C2 - 31949161
SN - 2041-1723
VL - 11
SP - 1
EP - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 312
ER -