Genomic risk prediction of coronary artery disease in women with breast cancer: a prospective cohort study.
Breast cancer
Cardiovascular disease
Coronary artery disease
Coronary heart disease
Polygenic risk score
SEARCH
Journal
Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353
Informations de publication
Date de publication:
30 09 2021
30 09 2021
Historique:
received:
12
04
2021
accepted:
24
08
2021
entrez:
1
10
2021
pubmed:
2
10
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Advancements in cancer therapeutics have resulted in increases in cancer-related survival; however, there is a growing clinical dilemma. The current balancing of survival benefits and future cardiotoxic harms of oncotherapies has resulted in an increased burden of cardiovascular disease in breast cancer survivors. Risk stratification may help address this clinical dilemma. This study is the first to assess the association between a coronary artery disease-specific polygenic risk score and incident coronary artery events in female breast cancer survivors. We utilized the Studies in Epidemiology and Research in Cancer Heredity prospective cohort involving 12,413 women with breast cancer with genotype information and without a baseline history of cardiovascular disease. Cause-specific hazard ratios for association of the polygenic risk score and incident coronary artery disease (CAD) were obtained using left-truncated Cox regression adjusting for age, genotype array, conventional risk factors such as smoking and body mass index, as well as other sociodemographic, lifestyle, and medical variables. Over a median follow-up of 10.3 years (IQR: 16.8) years, 750 incident fatal or non-fatal coronary artery events were recorded. A 1 standard deviation higher polygenic risk score was associated with an adjusted hazard ratio of 1.33 (95% CI 1.20, 1.47) for incident CAD. This study provides evidence that a coronary artery disease-specific polygenic risk score can risk-stratify breast cancer survivors independently of other established cardiovascular risk factors.
Sections du résumé
BACKGROUND
Advancements in cancer therapeutics have resulted in increases in cancer-related survival; however, there is a growing clinical dilemma. The current balancing of survival benefits and future cardiotoxic harms of oncotherapies has resulted in an increased burden of cardiovascular disease in breast cancer survivors. Risk stratification may help address this clinical dilemma. This study is the first to assess the association between a coronary artery disease-specific polygenic risk score and incident coronary artery events in female breast cancer survivors.
METHODS
We utilized the Studies in Epidemiology and Research in Cancer Heredity prospective cohort involving 12,413 women with breast cancer with genotype information and without a baseline history of cardiovascular disease. Cause-specific hazard ratios for association of the polygenic risk score and incident coronary artery disease (CAD) were obtained using left-truncated Cox regression adjusting for age, genotype array, conventional risk factors such as smoking and body mass index, as well as other sociodemographic, lifestyle, and medical variables.
RESULTS
Over a median follow-up of 10.3 years (IQR: 16.8) years, 750 incident fatal or non-fatal coronary artery events were recorded. A 1 standard deviation higher polygenic risk score was associated with an adjusted hazard ratio of 1.33 (95% CI 1.20, 1.47) for incident CAD.
CONCLUSIONS
This study provides evidence that a coronary artery disease-specific polygenic risk score can risk-stratify breast cancer survivors independently of other established cardiovascular risk factors.
Identifiants
pubmed: 34593009
doi: 10.1186/s13058-021-01465-0
pii: 10.1186/s13058-021-01465-0
pmc: PMC8482562
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
94Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/12/2/29428
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L003120/1
Pays : United Kingdom
Organisme : NIHR Newcastle Biomedical Research Centre
ID : C490/A16561
Informations de copyright
© 2021. The Author(s).
Références
Nat Genet. 2021 Apr;53(4):420-425
pubmed: 33692568
Circulation. 2016 Feb 9;133(6):601-9
pubmed: 26858290
Nat Genet. 2013 Apr;45(4):353-61, 361e1-2
pubmed: 23535729
J Am Coll Cardiol. 2020 Aug 11;76(6):703-714
pubmed: 32762905
Eur Heart J. 2016 Sep 21;37(36):2768-2801
pubmed: 27567406
J Cardiol. 2019 Apr;73(4):280-291
pubmed: 30587455
J Am Coll Cardiol. 2020 Jun 9;75(22):2781-2784
pubmed: 32498805
JAMA. 2019 May 14;321(18):1820-1821
pubmed: 30958510
Breast Cancer Res. 2011 Jun 20;13(3):R64
pubmed: 21689398
J Am Coll Cardiol. 2018 Oct 16;72(16):1883-1893
pubmed: 30309464
Circulation. 2017 May 30;135(22):2091-2101
pubmed: 28223407
Eur Heart J. 2016 Nov 14;37(43):3267-3278
pubmed: 27655226
N Engl J Med. 2013 Mar 14;368(11):987-98
pubmed: 23484825
Lancet. 2012 Feb 4;379(9814):432-44
pubmed: 22152853
Perm J. 2015 Spring;19(2):48-79
pubmed: 25902343
BMJ. 2017 May 23;357:j2099
pubmed: 28536104
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Postgrad Med J. 2017 Feb;93(1096):82-90
pubmed: 28123076
Genome Med. 2021 Jan 28;13(1):13
pubmed: 33509272
Lancet. 2005 May 14-20;365(9472):1687-717
pubmed: 15894097
Curr Treat Options Cardiovasc Med. 2019 Dec 9;21(12):79
pubmed: 31820123
Med Hypotheses. 2004;62(2):309-17
pubmed: 14962646
CA Cancer J Clin. 2016 Jul;66(4):309-25
pubmed: 26919165
JAMA. 2020 Feb 18;323(7):614-615
pubmed: 32068803
Hum Mol Genet. 2019 Nov 21;28(R2):R133-R142
pubmed: 31363735
Epidemiology. 2016 Jan;27(1):6-13
pubmed: 26414938
JAMA. 2020 Feb 18;323(7):636-645
pubmed: 32068818
Nat Genet. 2018 Sep;50(9):1219-1224
pubmed: 30104762
JAMA. 2020 Feb 18;323(7):627-635
pubmed: 32068817
Nature. 2017 Nov 2;551(7678):92-94
pubmed: 29059683
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593