Polygenic predisposition to breast cancer and the risk of coronary artery disease

Maria D'Souza; Morten Schou; Regitze Skals; Peter E. Weeke; Christina Lee; Lærke Smedegaard; Christian Madelaire; Thomas Alexander Gerds; Henrik Enghusen Poulsen; Torben Hansen; Niels Grarup; Oluf Pedersen; Steen Stender; Thomas Engstrøm; Emil Fosbøl; Dorte Nielsen; Gunnar Gislason; Lars Køber; Christian Torp-Pedersen; Charlotte Andersson

doi:10.1016/j.ijcard.2019.05.051

Polygenic predisposition to breast cancer and the risk of coronary artery disease

Maria D'Souza^*, Morten Schou, Regitze Skals, Peter E. Weeke, Christina Lee, Lærke Smedegaard, Christian Madelaire, Thomas Alexander Gerds, Henrik Enghusen Poulsen, Torben Hansen, Niels Grarup, Oluf Pedersen, Steen Stender, Thomas Engstrøm, Emil Fosbøl, Dorte Nielsen, Gunnar Gislason, Lars Køber, Christian Torp-Pedersen, Charlotte Andersson

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

Abstract

Background: Whether the increased risk of coronary artery disease (CAD) in patients with breast cancer may be linked to shared genetics is unknown. Our objective was to investigate the association of genetic predisposition to breast cancer with CAD risk via 1) a polygenic risk score 2) a nationwide case-control study.

Methods and results: We studied the associations of a polygenic risk score based on 91 single nucleotide polymorphisms previously associated with breast cancer in genome-wide association studies with the risk of CAD in a sample of patients undergoing coronary angiography. Secondary outcomes were prevalent atrial fibrillation, heart failure and breast cancer. Logistic regression models were used to analyze the associations. The risk of CAD associated with having a mother with breast cancer was analyzed with conditional logistic regression in the case-control study. Among 4985 patients undergoing coronary angiography (median age 66 years (Quartile (Q) 1-Q3 57–73), 65% male) 3724 (75%) had CAD. Increasing polygenic risk score was not associated with risks of CAD (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.94–1.08), atrial fibrillation (OR 1.03, CI 0.94–1.12), or heart failure (OR 0.97, CI 0.90–1.05). In women, increasing polygenic risk score was associated with the risk of breast cancer (OR 1.40, CI 1.14–1.73). The risk of CAD was not significantly increased in children with vs. without mothers with breast cancer (Hazard ratio 0.89 95% CI 0.83–0.96, p = 0.002).

Conclusions: Our study found no evidence of a shared genetic predisposition of breast cancer with CAD, atrial fibrillation, or heart failure.

Originalsprog	Engelsk
Tidsskrift	International Journal of Cardiology
Vol/bind	291
Sider (fra-til)	145-151
Antal sider	7
ISSN	0167-5273
DOI	https://doi.org/10.1016/j.ijcard.2019.05.051
Status	Udgivet - 2019

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10.1016/j.ijcard.2019.05.051

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D'Souza, M., Schou, M., Skals, R., Weeke, P. E., Lee, C., Smedegaard, L., Madelaire, C., Gerds, T. A., Poulsen, H. E., Hansen, T., Grarup, N., Pedersen, O., Stender, S., Engstrøm, T., Fosbøl, E., Nielsen, D., Gislason, G., Køber, L., Torp-Pedersen, C., & Andersson, C. (2019). Polygenic predisposition to breast cancer and the risk of coronary artery disease. International Journal of Cardiology, 291, 145-151. https://doi.org/10.1016/j.ijcard.2019.05.051

D'Souza, M, Schou, M, Skals, R, Weeke, PE, Lee, C, Smedegaard, L, Madelaire, C, Gerds, TA, Poulsen, HE , Hansen, T , Grarup, N , Pedersen, O , Stender, S , Engstrøm, T, Fosbøl, E, Nielsen, D, Gislason, G , Køber, L, Torp-Pedersen, C & Andersson, C 2019, 'Polygenic predisposition to breast cancer and the risk of coronary artery disease', International Journal of Cardiology, bind 291, s. 145-151. https://doi.org/10.1016/j.ijcard.2019.05.051

@article{12f724bd50a642dab6a0c4b97f5fc43e,

title = "Polygenic predisposition to breast cancer and the risk of coronary artery disease",

abstract = "Background: Whether the increased risk of coronary artery disease (CAD) in patients with breast cancer may be linked to shared genetics is unknown. Our objective was to investigate the association of genetic predisposition to breast cancer with CAD risk via 1) a polygenic risk score 2) a nationwide case-control study. Methods and results: We studied the associations of a polygenic risk score based on 91 single nucleotide polymorphisms previously associated with breast cancer in genome-wide association studies with the risk of CAD in a sample of patients undergoing coronary angiography. Secondary outcomes were prevalent atrial fibrillation, heart failure and breast cancer. Logistic regression models were used to analyze the associations. The risk of CAD associated with having a mother with breast cancer was analyzed with conditional logistic regression in the case-control study. Among 4985 patients undergoing coronary angiography (median age 66 years (Quartile (Q) 1-Q3 57–73), 65% male) 3724 (75%) had CAD. Increasing polygenic risk score was not associated with risks of CAD (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.94–1.08), atrial fibrillation (OR 1.03, CI 0.94–1.12), or heart failure (OR 0.97, CI 0.90–1.05). In women, increasing polygenic risk score was associated with the risk of breast cancer (OR 1.40, CI 1.14–1.73). The risk of CAD was not significantly increased in children with vs. without mothers with breast cancer (Hazard ratio 0.89 95% CI 0.83–0.96, p = 0.002). Conclusions: Our study found no evidence of a shared genetic predisposition of breast cancer with CAD, atrial fibrillation, or heart failure.",

keywords = "Atrial fibrillation, Breast cancer, Coronary artery disease, Genetic association studies, Heart failure",

author = "Maria D'Souza and Morten Schou and Regitze Skals and Weeke, {Peter E.} and Christina Lee and L{\ae}rke Smedegaard and Christian Madelaire and Gerds, {Thomas Alexander} and Poulsen, {Henrik Enghusen} and Torben Hansen and Niels Grarup and Oluf Pedersen and Steen Stender and Thomas Engstr{\o}m and Emil Fosb{\o}l and Dorte Nielsen and Gunnar Gislason and Lars K{\o}ber and Christian Torp-Pedersen and Charlotte Andersson",

note = "(Ekstern)",

year = "2019",

doi = "10.1016/j.ijcard.2019.05.051",

language = "English",

volume = "291",

pages = "145--151",

journal = "International Journal of Cardiology",

issn = "0167-5273",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Polygenic predisposition to breast cancer and the risk of coronary artery disease

AU - D'Souza, Maria

AU - Schou, Morten

AU - Skals, Regitze

AU - Weeke, Peter E.

AU - Lee, Christina

AU - Smedegaard, Lærke

AU - Madelaire, Christian

AU - Gerds, Thomas Alexander

AU - Poulsen, Henrik Enghusen

AU - Hansen, Torben

AU - Grarup, Niels

AU - Pedersen, Oluf

AU - Stender, Steen

AU - Engstrøm, Thomas

AU - Fosbøl, Emil

AU - Nielsen, Dorte

AU - Gislason, Gunnar

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Andersson, Charlotte

N1 - (Ekstern)

PY - 2019

Y1 - 2019

N2 - Background: Whether the increased risk of coronary artery disease (CAD) in patients with breast cancer may be linked to shared genetics is unknown. Our objective was to investigate the association of genetic predisposition to breast cancer with CAD risk via 1) a polygenic risk score 2) a nationwide case-control study. Methods and results: We studied the associations of a polygenic risk score based on 91 single nucleotide polymorphisms previously associated with breast cancer in genome-wide association studies with the risk of CAD in a sample of patients undergoing coronary angiography. Secondary outcomes were prevalent atrial fibrillation, heart failure and breast cancer. Logistic regression models were used to analyze the associations. The risk of CAD associated with having a mother with breast cancer was analyzed with conditional logistic regression in the case-control study. Among 4985 patients undergoing coronary angiography (median age 66 years (Quartile (Q) 1-Q3 57–73), 65% male) 3724 (75%) had CAD. Increasing polygenic risk score was not associated with risks of CAD (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.94–1.08), atrial fibrillation (OR 1.03, CI 0.94–1.12), or heart failure (OR 0.97, CI 0.90–1.05). In women, increasing polygenic risk score was associated with the risk of breast cancer (OR 1.40, CI 1.14–1.73). The risk of CAD was not significantly increased in children with vs. without mothers with breast cancer (Hazard ratio 0.89 95% CI 0.83–0.96, p = 0.002). Conclusions: Our study found no evidence of a shared genetic predisposition of breast cancer with CAD, atrial fibrillation, or heart failure.

AB - Background: Whether the increased risk of coronary artery disease (CAD) in patients with breast cancer may be linked to shared genetics is unknown. Our objective was to investigate the association of genetic predisposition to breast cancer with CAD risk via 1) a polygenic risk score 2) a nationwide case-control study. Methods and results: We studied the associations of a polygenic risk score based on 91 single nucleotide polymorphisms previously associated with breast cancer in genome-wide association studies with the risk of CAD in a sample of patients undergoing coronary angiography. Secondary outcomes were prevalent atrial fibrillation, heart failure and breast cancer. Logistic regression models were used to analyze the associations. The risk of CAD associated with having a mother with breast cancer was analyzed with conditional logistic regression in the case-control study. Among 4985 patients undergoing coronary angiography (median age 66 years (Quartile (Q) 1-Q3 57–73), 65% male) 3724 (75%) had CAD. Increasing polygenic risk score was not associated with risks of CAD (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.94–1.08), atrial fibrillation (OR 1.03, CI 0.94–1.12), or heart failure (OR 0.97, CI 0.90–1.05). In women, increasing polygenic risk score was associated with the risk of breast cancer (OR 1.40, CI 1.14–1.73). The risk of CAD was not significantly increased in children with vs. without mothers with breast cancer (Hazard ratio 0.89 95% CI 0.83–0.96, p = 0.002). Conclusions: Our study found no evidence of a shared genetic predisposition of breast cancer with CAD, atrial fibrillation, or heart failure.

KW - Atrial fibrillation

KW - Breast cancer

KW - Coronary artery disease

KW - Genetic association studies

KW - Heart failure

U2 - 10.1016/j.ijcard.2019.05.051

DO - 10.1016/j.ijcard.2019.05.051

M3 - Journal article

C2 - 31155334

AN - SCOPUS:85066267266

SN - 0167-5273

VL - 291

SP - 145

EP - 151

JO - International Journal of Cardiology

JF - International Journal of Cardiology

ER -

Polygenic predisposition to breast cancer and the risk of coronary artery disease

Abstract

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