A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
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.
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Escala-Garcia, Maria
be71247c-3e00-4f52-a8ab-080a12c9e657
Tapper, William
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
1 December 2020
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Escala-Garcia, Maria
be71247c-3e00-4f52-a8ab-080a12c9e657
Tapper, William
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Escala-Garcia, Maria
,
et al.
(2020)
A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.
Nature Communications, 11 (1), [312].
(doi:10.1038/s41467-019-14100-6).
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.
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Escala-Garcia_Pathway-MainText[09.08.19]_trackChanges
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Accepted/In Press date: 17 December 2019
e-pub ahead of print date: 16 January 2020
Published date: 1 December 2020
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© 2020, The Author(s).
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Local EPrints ID: 439145
URI: http://eprints.soton.ac.uk/id/eprint/439145
ISSN: 2041-1723
PURE UUID: deddde2f-ed8e-4d4a-bbc1-164fc8ddcf19
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Date deposited: 06 Apr 2020 16:30
Last modified: 06 Jun 2024 04:03
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Author:
Maria Escala-Garcia
Corporate Author: et al.
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