ISSN (print) 1997-6933     ISSN (online) 2500-2139
Vol. 17 No. 2 (2024), LYMPHOID TUMORS
Vol. 17 No. 2 (2024)
LYMPHOID TUMORS

The Role of Polymorphic Variants of Р450 Cytochrome Genes as well as Genes GSTP1 and MDR1 in Toxic Complications of Program Drug Chemotherapy for Classical Hodgkin Lymphoma

Published 01.04.2024
Yana Yurevna Shebunyaeva
Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091
PDF_2024-17-2_141-153 (Russian)

Keywords

classical Hodgkin lymphoma
hepatotoxicity
cardiotoxicity
gene polymorphism
cytochromes Р450
genes MDR1
GSTP1

How to Cite

Shebunyaeva Y.Y. The Role of Polymorphic Variants of Р450 Cytochrome Genes as well as Genes GSTP1 and MDR1 in Toxic Complications of Program Drug Chemotherapy for Classical Hodgkin Lymphoma. Clinical Oncohematology. 2024;(2):141–153. doi:10.21320/2500-2139-2024-17-2-141-153.
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Abstract

Background. Although considerable progress has been achieved in the treatment of classical Hodgkin lymphoma (cHL), toxic complications of program drug chemotherapy remain an issue. Standard cytostatic agents used in cHL therapy are metabolized in liver by the enzymes with Р450 cytochrome and GSTP1 gene-controlled synthesis. At the same time, the excretion of active metabolites of antitumor drugs is mediated by MDR1 coded P-glycoprotein. Polymorphisms[1] of these genes may change the processes of antitumor drug biotransformation and their metabolite excretion. Additionally, they may result in organo-toxic complications, disablement of patients, and even death.

Aim. To assess the role of polymorphisms in cytochrome genes Р450 as well as genes GSTP1 and MDR1 in organ toxicity dynamics during program chemotherapy (CT) in cHL patients.

Materials & Methods. The study enrolled 122 cHL patients treated with first-line regimens (ABVD, BEACOPP) of program drug chemotherapy. The patients were aged 18–78 years (median 35 years); there were 67 (54.9 %) women and 55 (45.1 %) men. In compliance with the NCCN CTC (2003) criteria of hepatotoxicity and practical recommendations for correcting cardiovascular toxicity of chemotherapy (2021), the signs of toxic liver and heart damage were assessed in all patients. PCR was used to analyze polymorphisms in cytochrome genes Р450 as well as genes GSTP1 and MDR1, their association with toxic complications of CT was analyzed.

Results. Drug-induced liver damage on program CT was identified in 80 % of cHL patients. The toxicity was increasing from CT cycle 1 to cycle 6 both on ABVD and BEACOPP. Complications grade 3/4 were observed only in BEACOPP recipients. Significant (p < 0.05) associations were found between hepatotoxic complications with increased cytolytic (AST, ALT) and cholestatic (ALP) values and polymorphic variants of MDR1. Significant (p < 0.05) reduction of left ventricle myocardium contractility in cHL patients was associated with Т-allele presence in genotypes CYP2D6*10 (rs1065852), CYP2C9*2 (rs1799853) and A-allele deletion in genotype CYP2D6_3 (rs4986774).

Conclusion. The identification of genetic predictors for toxic effects of program CT in cHL patients at the baseline examination can minimize the risks of drug chemotherapy-related adverse events and allow these patients to maintain a satisfactory quality of life.

 

[1] Gene polymorphism is a structural difference between alternative variants of a gene. Alternative variants of genes result from mutations.

PDF_2024-17-2_141-153 (Russian)

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