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
PY - 2019/9/15
Y1 - 2019/9/15
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.
U2 - 10.1016/j.ijcard.2019.05.051
DO - 10.1016/j.ijcard.2019.05.051
M3 - Journal article
C2 - 31155334
SN - 0167-5273
VL - 291
SP - 145
EP - 151
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -