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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Escala-Garcia, Maria 
Abraham, Jean 
Anton-Culver, Hoda 

Abstract

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.

Description

Keywords

Journal Title

Nature communications

Conference Name

Journal ISSN

2041-1723

Volume Title

11

Publisher

Sponsorship
NHLBI NIH HHS (HHSN268201100046C, HHSN268201100001I, HHSN268201100002I, HHSN268201100004I)
NIA NIH HHS (HHSN271201100004C)
NCI NIH HHS (P50 CA116201, R01 CA128931, U01 CA098758, U01 CA179715, U19 CA148065, R01 CA097396, R01 CA177150, R01 CA192393, UM1 CA164917, UM1 CA164920, UM1 CA164973, UM1 CA176726, P50 CA058223, R01 CA063464, R01 CA132839, U01 CA063464, U01 CA164973, U19 CA148112, K07 CA092044, P01 CA087969, R01 CA140286, R01 CA176785, R37 CA054281, U01 CA058860, U01 CA116167, UM1 CA186107, R01 CA054281, U19 CA148537, R01 CA058860, R01 CA077398, R01 CA116167, R01 CA128978, U01 CA199277, U54 CA156733)
WHI NIH HHS (HHSN268201100003C, HHSN268201100001C, HHSN268201100002C, HHSN268201100004C)
Cancer Foundation Finland sr (160104)
European Research Council (294576)