Genome-wide association study of germline variants and breast cancer-specific mortality.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
06
08
2018
accepted:
14
01
2019
revised:
02
01
2019
pubmed:
23
2
2019
medline:
18
12
2019
entrez:
22
2
2019
Statut:
ppublish
Résumé
We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10 We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.
Sections du résumé
BACKGROUND
We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.
METHODS
Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).
RESULTS
We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10
CONCLUSIONS
We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.
Identifiants
pubmed: 30787463
doi: 10.1038/s41416-019-0393-x
pii: 10.1038/s41416-019-0393-x
pmc: PMC6461853
doi:
Substances chimiques
Receptors, Estrogen
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
647-657Subventions
Organisme : NCI NIH HHS
ID : UM1 CA164973
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA176785
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100004I
Pays : United States
Organisme : NCI NIH HHS
ID : K07 CA092044
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA116167
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA128978
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA098758
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100002I
Pays : United States
Organisme : Medical Research Council
ID : G0700491
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA192393
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA164917
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199277
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA179715
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA128931
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100001I
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA156733
Pays : United States
Organisme : Cancer Research UK
ID : 10124
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P01 CA087969
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA164920
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA097396
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA176726
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100046C
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA058860
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100003C
Pays : United States
Organisme : Medical Research Council
ID : MR/N003284/1
Pays : United Kingdom
Organisme : Department of Health
ID : RP-PG-1214-20016
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P50 CA058223
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148537
Pays : United States
Organisme : Medical Research Council
ID : G0401527
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA116167
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA177150
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA116201
Pays : United States
Organisme : Department of Health
ID : RP-PG-0707-10031
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : HHSN271201100004C
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA063464
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186107
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100002C
Pays : United States
Organisme : Medical Research Council
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Pays : United Kingdom
Organisme : NCI NIH HHS
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Pays : United States
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Pays : United States
Organisme : NCI NIH HHS
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Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA132839
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA058860
Pays : United States
Organisme : Cancer Research UK
ID : 10118
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 14136
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U19 CA148112
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148065
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100003I
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006927
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA054281
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100001C
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164973
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA140286
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100004C
Pays : United States
Organisme : Cancer Research UK
ID : 10119
Pays : United Kingdom
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