CONFERENCE PROCEEDING
The level of trace elements and cytochrome cyp2d6 polymorphism in survivors of hemoblastosis complicated by the development of metabolic syndrome
1
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
2
Skolkovo Institute of Science and Technology, Moscow, Russia
3
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, Moscow, Russia
4
Peoples’ Friendship University of Russia named after Patrice Lumumba, Moscow, Russia
5
I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
Publication date: 2026-07-30
Public Health Toxicol 2026;6(Supplement 1):A21
KEYWORDS
trace elementmanganeseironcadmiumcytochromechildrenhairshemoblastosisserumsalivainductively coupled plasma mass spectrometryinsulin resistancegenetic polymorphism
ABSTRACT
Introduction:
More than 30% of patients treated for childhood malignancies develop various metabolic disorders (dyslipidemia, insulin resistance, and obesity) during rehabilitation. The formation of insulin resistance and obesity may be associated with impaired metabolism of essential elements, as well as exposure to toxic metals. The levels of trace elements and minerals in the blood serum can lead to metabolic changes in obese individuals1. Hereditary predisposition, including polymorphisms in cytochrome P450 genes involved in chemotherapy drug metabolism, is also significant, as these variations are associated with clinical outcomes and toxicity2. This study aimed to analyze the association between metabolic disorders, levels of essential and toxic trace elements, and the frequency of CYP450 allelic variants in survivors.
Methods:
The study included 214 children, 95 girls and 119 boys with hemoblastosis, who got rehabilitation course at the Russian Field Medical Center. The average age was 10.2 years (from 4.9 to 17.6 years), the duration of remission was 4.6 years (from 0.8 to 12.5 years). Body mass index (BMI), fasting glucose, NOME-IR index, and cholesterol levels were determined. The NGS method was used to study the coding regions of genes involved in the metabolism of antitumor drugs. The levels of toxic and essential trace elements were determined by the ICP-MS method. The search for correlations was carried out using Spearman's criterion. Various machine learning models were used and the permutation method was applied.
Results:
43% of patients were overweight, including 16% with obesity (+2.0 SDS BMI). Insulin resistance (HOMA-IR >3.2) was found in 23% of children, and a combination of at least two metabolic disorders (insulin resistance and overweight) occurred in 14% of patients. Strong positive correlation was observed in the patients' hair between the levels of toxic elements, primarily lead and cadmium, as well as arsenic, manganese and iron, and their negative correlation with zinc levels. The insulin resistance index and body mass index were positively correlated with the level of zinc and negatively with the level of toxic metals in the hair, which makes it possible to use the value of trace elements as prognostic risk factors for metabolic syndrome.
Conclusion:
Using machine learning methods, the importance of the genetic polymorphism of the CYP2D6 gene associated with the individual body's ability to detoxify has been revealed for the development of insulin resistance and an increase in BMI.
More than 30% of patients treated for childhood malignancies develop various metabolic disorders (dyslipidemia, insulin resistance, and obesity) during rehabilitation. The formation of insulin resistance and obesity may be associated with impaired metabolism of essential elements, as well as exposure to toxic metals. The levels of trace elements and minerals in the blood serum can lead to metabolic changes in obese individuals1. Hereditary predisposition, including polymorphisms in cytochrome P450 genes involved in chemotherapy drug metabolism, is also significant, as these variations are associated with clinical outcomes and toxicity2. This study aimed to analyze the association between metabolic disorders, levels of essential and toxic trace elements, and the frequency of CYP450 allelic variants in survivors.
Methods:
The study included 214 children, 95 girls and 119 boys with hemoblastosis, who got rehabilitation course at the Russian Field Medical Center. The average age was 10.2 years (from 4.9 to 17.6 years), the duration of remission was 4.6 years (from 0.8 to 12.5 years). Body mass index (BMI), fasting glucose, NOME-IR index, and cholesterol levels were determined. The NGS method was used to study the coding regions of genes involved in the metabolism of antitumor drugs. The levels of toxic and essential trace elements were determined by the ICP-MS method. The search for correlations was carried out using Spearman's criterion. Various machine learning models were used and the permutation method was applied.
Results:
43% of patients were overweight, including 16% with obesity (+2.0 SDS BMI). Insulin resistance (HOMA-IR >3.2) was found in 23% of children, and a combination of at least two metabolic disorders (insulin resistance and overweight) occurred in 14% of patients. Strong positive correlation was observed in the patients' hair between the levels of toxic elements, primarily lead and cadmium, as well as arsenic, manganese and iron, and their negative correlation with zinc levels. The insulin resistance index and body mass index were positively correlated with the level of zinc and negatively with the level of toxic metals in the hair, which makes it possible to use the value of trace elements as prognostic risk factors for metabolic syndrome.
Conclusion:
Using machine learning methods, the importance of the genetic polymorphism of the CYP2D6 gene associated with the individual body's ability to detoxify has been revealed for the development of insulin resistance and an increase in BMI.
CONFLICTS OF INTEREST
The authors declare that they have no conflicts of interest in the publication of this article. The authors have no conflicts of interest to report in this work. Abstract was not submitted elsewhere and is first published here.
FUNDING
This work was funded by the Ministry of Science and Higher Education of the Russian Federation.
REFERENCES (2)
1.
Tinkov AA, Bogdański P, Skrypnik D, et al. Trace element and mineral levels in serum, hair, and urine of obese women in relation to body composition, blood pressure, lipid profile, and insulin resistance. Biomolecules. 2021;11(5):689. doi:10.3390/biom11050689
2.
Charo LM, Homer MV, Natarajan L, et al. Drug metabolising enzyme polymorphisms and chemotherapy-related ovarian failure in young breast cancer survivors. J Obstet Gynaecol. 2021;41(3):447-452. doi:10.1080/01443615.2020.1754369
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