Key result
RARG rs2229774 AA genotype links to doxorubicin-induced cardiotoxicity while the SLC28A3 rs7853758 variant appears protective.
Why the study?
To determine the role of RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 single-nucleotide polymorphisms in identifying the risk of doxorubicin-induced cardiotoxicity in pediatric solid tumors.
Do RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 polymorphisms predict doxorubicin-induced cardiotoxicity in pediatric patients with solid tumors?
Observational (n=110)
Do RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 polymorphisms predict doxorubicin-induced cardiotoxicity in pediatric patients with solid tumors?
RARG rs2229774 and SLC28A3 rs7853758 polymorphisms are useful for predicting the risk of doxorubicin-induced cardiotoxicity in pediatric solid tumor patients.
Hypothesis-generating for pharmacogenomic prediction; leaves open whether RARG/SLC28A3 variants should guide doxorubicin use in children.
BACKGROUND: The objective of our study was to determine the role of retinoic acid receptor gamma (RARG) rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 single-nucleotide polymorphisms in identifying the risk of doxorubicin-induced cardiotoxicity in pediatric solid tumors. METHODS: A total of 60 pediatric patients who had completed their treatment at least 2 years ago and 50 healthy children matched for age and sex were included in the study. All patients were evaluated for cardiotoxicity by echocardiography. The blood samples were analyzed for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 polymorphisms. Demographic characteristics, echocardiographic parameters, and genetic results of both groups were evaluated. RESULTS: In our study, the RARG rs2229774 AA genotype was associated with cardiotoxicity ( P =0.017). The SLC28A3 rs7853758 AA+GA genotype was detected more frequently in patients who did not develop cardiotoxicity ( P <0.023). Furthermore, the frequency of the SLC28A3 rs7853758 A allele was significantly lower in the cardiotoxicity group ( P <0.025). CONCLUSIONS: This is the first study in the Turkish population to investigate the correlation between the cardiotoxicity risk and 3 marker genes, which are recommended in the pharmacogenetic guideline for risk assessment in pediatric doxorubicin patients. The gene polymorphism that we investigated in this study was useful for the early prediction of cardiotoxicity risk.
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Gündüz et al. (2023) conducted an observational in Doxorubicin-induced cardiotoxicity in pediatric solid tumors (n=110). RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 polymorphisms vs. Absence of these specific genotypes was evaluated on Doxorubicin-induced cardiotoxicity (p=0.017). The RARG rs2229774 AA genotype was associated with doxorubicin-induced cardiotoxicity (P=0.017), while the SLC28A3 rs7853758 AA+GA genotype was more frequent in patients without cardiotoxicity (P<0.023).
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