| Full text | |
| Author(s): |
Quintanilha, Julia C. F.
[1]
;
Racioppi, Alessandro
[1]
;
Wang, Jin
[2]
;
Etheridge, Amy S.
[1]
;
Denning, Stefanie
[1]
;
Pena, Carol E.
[3]
;
Skol, Andrew D.
[4]
;
Crona, Daniel J.
[5, 1, 6]
;
Lin, Danyu
[2]
;
Innocenti, Federico
[1]
Total Authors: 10
|
| Affiliation: | [1] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Eshelman Sch Pharm, Chapel Hill, NC 27515 - USA
[2] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 - USA
[3] Bayer Hlth Care Pharmaceut, Whippany, NJ - USA
[4] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 - USA
[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 - USA
[6] Univ N Carolina, Dept Pharm, Med Ctr, Chapel Hill, NC 27515 - USA
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | PHARMACOGENOMICS JOURNAL; v. 22, n. 1 NOV 2021. |
| Web of Science Citations: | 1 |
| Abstract | |
No biomarkers are available to predict patients at risk of developing hypertension induced by VEGF-pathway inhibitors. This study aimed to identify predictive biomarkers of hypertension induced by these drugs using a discovery-replication approach. The discovery set included 140 sorafenib-treated patients (TARGET study) genotyped for 973 SNPs in 56 genes. The most statistically significant SNPs associated with grade >= 2 hypertension were tested for association with grade >= 2 hypertension in the replication set of a GWAS of 1039 bevacizumab-treated patients from four clinical trials (CALGB/Alliance). In the discovery set, rs444904 (G > A) in PIK3R5 was associated with an increased risk of sorafenib-induced hypertension (p = 0.006, OR = 3.88 95% CI 1.54-9.81). In the replication set, rs427554 (G > A) in PIK3R5 (in complete linkage disequilibrium with rs444904) was associated with an increased risk of bevacizumab-induced hypertension (p = 0.008, OR = 1.39, 95% CI 1.09-1.78). This study identified a predictive marker of drug-induced hypertension that should be evaluated for other VEGF-pathway inhibitors. ClinicalTrials.gov Identifier:NCT00073307 (TARGET). (AU) | |
| FAPESP's process: | 18/04491-2 - Genetic susceptibility to severe toxicities and toxic deaths among 1,626 cancer patients trated with bevacizumab: implications for treatment and personalized therapy |
| Grantee: | Júlia Coelho França Quintanilha |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |