Contribution of Polygenic Risk to Hypertension Among Long-Term Survivors of Childhood Cancer

BACKGROUND Childhood cancer survivors experience significantly higher rates of hypertension, which potentiates cardiovascular disease, but the contribution and relationship of genetic and treatment factors to hypertension risk are unknown. OBJECTIVES This study sought to determine the contribution of a blood pressure potygenic risk score (PRS) from the general population and its interplay with cancer therapies to hypertension in childhood cancer survivors. METHODS Using 895 established blood pressure loci from the general population, we calculated a PRS for 3,572 childhood cancer survivors of European ancestry from the Childhood Cancer Survivor Study (CCSS) original cohort, 1,889 from the CCSS expansion cohort, and 2,534 from the St. Jude Lifetime Cohort. Hypertension was assessed using National Cancer Institute criteria based on self-report of a physician diagnosis in CCSS and based on blood pressure measurement in the St. Jude Lifetime Cohort. RESULTS In the combined sample of 7,995 survivors, those in the top decile of the PRS had an odds ratio (OR) of 2.66 (95% confidence interval (CI]: 2.03 to 3.48) for hypertension compared with survivors in the bottom decile. The PRS-hypertension association was modified by being overweight/obese (per standard deviation interaction OR: 1.13; 95% 0: 1.01 to 1.27) and exposure to hypothalamic-pituitary axis radiation (per standard deviation interaction OR: 1.18; 95% CI: 1.05 to 1.33). Attributable fractions for hypertension to the PRS and cancer therapies were 21.0% and 15.7%, respectively; they jointly accounted for 40.2% of hypertension among survivors. CONCLUSIONS A blood pressure PRS from the general population is significantly associated with hypertension among childhood cancer survivors and contributes to approximately one quarter of hypertension risk among survivors. These findings highlight the importance of screening for hypertension in all childhood cancer survivors and identifying higher-risk subgroups. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.