Background sensitivity to chemotherapy-induced nausea and vomiting and response to antiemetics in paediatric patients: a genetic association study
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Background sensitivity to chemotherapy-induced nausea and vomiting and response to antiemetics in paediatric patients : a genetic association study. / Eliasen, Astrid; Kornholt, Jonatan; Mathiasen, René; Wadt, Karin; Stoltze, Ulrik; Brok, Jesper; Rechnitzer, Catherine; Schmiegelow, Kjeld; Dalhoff, Kim.
I: Pharmacogenetics and Genomics, Bind 32, Nr. 2, 2022, s. 72-78.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Background sensitivity to chemotherapy-induced nausea and vomiting and response to antiemetics in paediatric patients
T2 - a genetic association study
AU - Eliasen, Astrid
AU - Kornholt, Jonatan
AU - Mathiasen, René
AU - Wadt, Karin
AU - Stoltze, Ulrik
AU - Brok, Jesper
AU - Rechnitzer, Catherine
AU - Schmiegelow, Kjeld
AU - Dalhoff, Kim
N1 - Publisher Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2022
Y1 - 2022
N2 - Chemotherapy-induced nausea and vomiting (CINV) remains a common adverse effect for children with cancer. In children, chemotherapy emetogenicity and patient factors such as susceptibility to motion sickness and age group determine a patient’s risk of CINV. Besides known risk factors, genetic factors may play a role in interindividual variation in the occurrence of CINV. We investigated the influence of candidate gene polymorphisms on the efficacy of antiemetics and on the background sensitivity to CINV in children. This prospective study included 100 children with cancer (median age 6.4 years, range 0.8–17.9) who received moderately to highly emetogenic chemotherapy. Participants registered nausea and vomiting episodes in a mobile app. Genotypes were determined by whole-genome sequencing (n = 79) or Sanger sequencing (n = 21) for 71 genetic polymorphisms involved in motion sickness and antiemetic pathways. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate associations between acute CINV and genotypes adjusting for susceptibility to motion sickness and age group. Rs3782025 in the 5-hydroxytryptamine type 3 (5-HT3) receptor gene (HTR3B) [minor allele frequency (MAF): 0.48] affected response to 5-HT3 receptor antagonists; acute CINV occurred in 76% of patients with GA/AA genotypes and in 41% of patients with GG genotype (OR 5.59; 95% CI 1.74–17.9, dominant genetic model). Rs2975226 in the dopamine transporter gene (SLC6A3) (MAF: 0.54) was associated with acute CINV (OR 5.79; 95% CI 1.09–30.67, recessive genetic model). Polymorphisms in HTR3B and SLC6A3 may contribute to the variability in response to antiemetic prophylaxis for CINV in children.
AB - Chemotherapy-induced nausea and vomiting (CINV) remains a common adverse effect for children with cancer. In children, chemotherapy emetogenicity and patient factors such as susceptibility to motion sickness and age group determine a patient’s risk of CINV. Besides known risk factors, genetic factors may play a role in interindividual variation in the occurrence of CINV. We investigated the influence of candidate gene polymorphisms on the efficacy of antiemetics and on the background sensitivity to CINV in children. This prospective study included 100 children with cancer (median age 6.4 years, range 0.8–17.9) who received moderately to highly emetogenic chemotherapy. Participants registered nausea and vomiting episodes in a mobile app. Genotypes were determined by whole-genome sequencing (n = 79) or Sanger sequencing (n = 21) for 71 genetic polymorphisms involved in motion sickness and antiemetic pathways. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate associations between acute CINV and genotypes adjusting for susceptibility to motion sickness and age group. Rs3782025 in the 5-hydroxytryptamine type 3 (5-HT3) receptor gene (HTR3B) [minor allele frequency (MAF): 0.48] affected response to 5-HT3 receptor antagonists; acute CINV occurred in 76% of patients with GA/AA genotypes and in 41% of patients with GG genotype (OR 5.59; 95% CI 1.74–17.9, dominant genetic model). Rs2975226 in the dopamine transporter gene (SLC6A3) (MAF: 0.54) was associated with acute CINV (OR 5.79; 95% CI 1.09–30.67, recessive genetic model). Polymorphisms in HTR3B and SLC6A3 may contribute to the variability in response to antiemetic prophylaxis for CINV in children.
KW - Adolescents
KW - Antiemetics
KW - Chemotherapy-induced nausea and vomiting
KW - Children
KW - Mobile health
KW - Patient-related risk factors
KW - Pharmacogenetics
U2 - 10.1097/FPC.0000000000000460
DO - 10.1097/FPC.0000000000000460
M3 - Journal article
C2 - 34750329
AN - SCOPUS:85122299021
VL - 32
SP - 72
EP - 78
JO - Pharmacogenetics
JF - Pharmacogenetics
SN - 1744-6872
IS - 2
ER -
ID: 290110139