Research
Print page Print page
Switch language
Bispebjerg Hospital - a part of Copenhagen University Hospital
Published

Background sensitivity to chemotherapy-induced nausea and vomiting and response to antiemetics in paediatric patients: a genetic association study

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Pharmacogenetics and individual responses to treatment of hyperglycemia in type 2 diabetes

    Research output: Contribution to journalReviewResearchpeer-review

  2. Angiotensinogen and ACE gene polymorphisms and risk of atrial fibrillation in the general population.

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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.

Original languageEnglish
JournalPharmacogenetics and Genomics
Volume32
Issue number2
Pages (from-to)72-78
Number of pages7
ISSN1744-6872
DOIs
Publication statusPublished - 1 Feb 2022

Bibliographical note

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

    Research areas

  • adolescents, antiemetics, chemotherapy-induced nausea and vomiting, children, mobile health, patient-related risk factors, pharmacogenetics

ID: 68915898