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.