{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:21:56Z","timestamp":1776399716523,"version":"3.51.2"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T00:00:00Z","timestamp":1653091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>Hypertension is a common bevacizumab\u2010induced toxicity. No markers are available to predict patients at risk of developing hypertension. We hypothesized that genetic risk of essential hypertension, as measured by a blood pressure polygenic risk score (PRS), would be associated with risk of severe bevacizumab\u2010induced hypertension. PRSs were calculated for 1,027 bevacizumab\u2010treated patients of European descent with cancer from four clinical trials (Alliance for Clinical Trials in Oncology (Alliance) \/ Cancer and Leukemia Group B (CALGB) 80303, 40503, 90401, 40502) using summary systolic blood pressure (SBP) and diastolic blood pressure (DBP) genome\u2010wide association results obtained from 757,601 individuals of European descent. The association between PRS and grade 3 bevacizumab\u2010induced hypertension (Common Toxicity Criteria for Adverse Events version 3) in each trial was performed by multivariable logistic regression. Fixed\u2010effect meta\u2010analyses odds ratios (ORs) per standard deviation (SD) of the association of PRS (quantitative) and hypertension across trials were estimated by inverse\u2010variance weighting. PRSs were additionally stratified into quintiles, with the bottom quintile as the referent group. The OR of the association between hypertension and each quintile vs. the referent group was determined by logistic regression. The most significant PRS (quantitative)\u2010hypertension association included up to 67 single\u2010nucleotide variants (SNPs) associated with SBP (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0077, OR per SD\u00a0=\u00a01.31, 95% confidence interval (CI), 1.07\u20131.60), and up to 53 SNPs associated with DBP (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0209, OR per SD\u00a0=\u00a01.27, 95% CI, 1.04\u20131.56). Patients in the top quintile had a higher risk of developing bevacizumab\u2010induced hypertension compared with patients in the bottom quintile using SNPs associated with SBP (<jats:italic>P<\/jats:italic>\u00a0=\u00a04.75\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>, OR\u00a0=\u00a03.72, 95% CI, 1.84\u20138.16) and DBP (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.076, OR\u00a0=\u00a01.83, 95% CI, 0.95\u20133.64). Genetic variants associated with essential hypertension, mainly SBP, increase the risk of severe bevacizumab\u2010induced hypertension.<\/jats:p>","DOI":"10.1002\/cpt.2635","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T06:29:20Z","timestamp":1652077760000},"page":"364-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Polygenic Risk Scores for Blood Pressure to Assess the Risk of Severe Bevacizumab\u2010Induced Hypertension in Cancer Patients (Alliance)"],"prefix":"10.1111","volume":"112","author":[{"given":"Julia C.F.","family":"Quintanilha","sequence":"first","affiliation":[{"name":"University of North Carolina Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy S.","family":"Etheridge","sequence":"additional","affiliation":[{"name":"University of North Carolina Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brady J.","family":"Graynor","sequence":"additional","affiliation":[{"name":"School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas B.","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Crona","sequence":"additional","affiliation":[{"name":"University of North Carolina Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Lineberger Comprehensive Cancer Center University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Braxton D.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Innocenti","sequence":"additional","affiliation":[{"name":"AbbVie, Inc.  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