Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene
Background: Vincristine polyneuropathy is a major neurotoxic complication of treatment for acute lymphoblastic leukemia in children. A close relationship between genetic variants in candidate genes associated with the vincristine neurotoxicity in various ethnic groups has been proposed. Therefore, i...
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| Format: | Article |
| Language: | Russian |
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MONIKI
2023-08-01
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| Series: | Alʹmanah Kliničeskoj Mediciny |
| Subjects: | |
| Online Access: | https://almclinmed.ru/jour/article/viewFile/11753/1571 |
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| author | Oksana V. Koryakina Olga P. Kovtun Grigory A. Tsaur Elena V. Tsyganko Larisa G. Fechina Vladimir V. Bazarnyi |
| author_facet | Oksana V. Koryakina Olga P. Kovtun Grigory A. Tsaur Elena V. Tsyganko Larisa G. Fechina Vladimir V. Bazarnyi |
| author_sort | Oksana V. Koryakina |
| collection | DOAJ |
| description | Background: Vincristine polyneuropathy is a major neurotoxic complication of treatment for acute lymphoblastic leukemia in children. A close relationship between genetic variants in candidate genes associated with the vincristine neurotoxicity in various ethnic groups has been proposed. Therefore, identification of the genetic risk factors underlying the predisposition to vincristine polyneuropathy could allow the development of effective tools for preventive diagnostics aimed at identifying a high-risk group among patients treated with vincristine for a personalized approach to their chemotherapy.
Aim: To study an association between the rs924607 polymorphism of the CEP72 gene and vincristine polyneuropathy in children with acute lymphoblastic leukemia.
Materials and methods: This single center cohort study enrolled 199 children aged 3 to 17 years with newly diagnosed acute lymphoblastic leukemia, who received ALL-MB 2015 chemotherapy regimen. All patients were genotyped for the single nucleotide variant rs924607 in the CEP72 gene by real-time polymerase chain reaction and subsequent allelic discrimination. A comparative analysis of the incidence and clinical signs of vincristine polyneuropathy depending on the carrier of the genetic polymorphism was performed.
Results: The incidence of vincristine polyneuropathy in the study pediatric group was 81.0% (n = 161); mostly these were patients with NCI-STCAE grade 2 severity. The rs924607 single nucleotide variant in the CEP72 gene was significantly associated with the neurotoxic complication, with 19.1% (n = 38) of the patients were homozygous for the minor allele (rs924607 genotype TT) and 46.2% (n = 92) had the ST genotype. Among the carriers of at least one rs924607 risk allele (T), the odds ratio for vincristine polyneuropathy was 2.91 (95% confidence interval 1.415.99, p = 0.004). No significant association between the genetic variant assessed and clinical signs of vincristine-induced polyneuropathy was found.
Conclusion: The single nucleotide rs924607 polymorphism of the CEP72 gen can be a putative pharmacogenetic marker for vincristine polyneuropathy. |
| first_indexed | 2024-03-12T14:58:56Z |
| format | Article |
| id | doaj.art-d661a9ed961648e98b9af0993299342c |
| institution | Directory Open Access Journal |
| issn | 2072-0505 2587-9294 |
| language | Russian |
| last_indexed | 2024-03-12T14:58:56Z |
| publishDate | 2023-08-01 |
| publisher | MONIKI |
| record_format | Article |
| series | Alʹmanah Kliničeskoj Mediciny |
| spelling | doaj.art-d661a9ed961648e98b9af0993299342c2023-08-14T11:15:06ZrusMONIKIAlʹmanah Kliničeskoj Mediciny2072-05052587-92942023-08-0151316317010.18786/2072-0505-2023-51-016936Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> geneOksana V. Koryakina0https://orcid.org/0000-0002-4595-1024Olga P. Kovtun1https://orcid.org/0000-0002-5250-7351Grigory A. Tsaur2https://orcid.org/0000-0002-9881-6221Elena V. Tsyganko3Larisa G. Fechina4https://orcid.org/0000-0002-1885-3912Vladimir V. Bazarnyi5https://orcid.org/0000-0003-0966-9571Ural State Medical UniversityUral State Medical UniversityUral State Medical UniversityRegional Children's Clinical Hospital, YekaterinburgRegional Children's Clinical Hospital, YekaterinburgUral State Medical UniversityBackground: Vincristine polyneuropathy is a major neurotoxic complication of treatment for acute lymphoblastic leukemia in children. A close relationship between genetic variants in candidate genes associated with the vincristine neurotoxicity in various ethnic groups has been proposed. Therefore, identification of the genetic risk factors underlying the predisposition to vincristine polyneuropathy could allow the development of effective tools for preventive diagnostics aimed at identifying a high-risk group among patients treated with vincristine for a personalized approach to their chemotherapy. Aim: To study an association between the rs924607 polymorphism of the CEP72 gene and vincristine polyneuropathy in children with acute lymphoblastic leukemia. Materials and methods: This single center cohort study enrolled 199 children aged 3 to 17 years with newly diagnosed acute lymphoblastic leukemia, who received ALL-MB 2015 chemotherapy regimen. All patients were genotyped for the single nucleotide variant rs924607 in the CEP72 gene by real-time polymerase chain reaction and subsequent allelic discrimination. A comparative analysis of the incidence and clinical signs of vincristine polyneuropathy depending on the carrier of the genetic polymorphism was performed. Results: The incidence of vincristine polyneuropathy in the study pediatric group was 81.0% (n = 161); mostly these were patients with NCI-STCAE grade 2 severity. The rs924607 single nucleotide variant in the CEP72 gene was significantly associated with the neurotoxic complication, with 19.1% (n = 38) of the patients were homozygous for the minor allele (rs924607 genotype TT) and 46.2% (n = 92) had the ST genotype. Among the carriers of at least one rs924607 risk allele (T), the odds ratio for vincristine polyneuropathy was 2.91 (95% confidence interval 1.415.99, p = 0.004). No significant association between the genetic variant assessed and clinical signs of vincristine-induced polyneuropathy was found. Conclusion: The single nucleotide rs924607 polymorphism of the CEP72 gen can be a putative pharmacogenetic marker for vincristine polyneuropathy.https://almclinmed.ru/jour/article/viewFile/11753/1571vincristineneurotoxicityacute leukemiapolyneuropathygenetic variantcep72 |
| spellingShingle | Oksana V. Koryakina Olga P. Kovtun Grigory A. Tsaur Elena V. Tsyganko Larisa G. Fechina Vladimir V. Bazarnyi Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene Alʹmanah Kliničeskoj Mediciny vincristine neurotoxicity acute leukemia polyneuropathy genetic variant cep72 |
| title | Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene |
| title_full | Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene |
| title_fullStr | Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene |
| title_full_unstemmed | Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene |
| title_short | Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene |
| title_sort | vincristine polyneuropathy in children with acute lymphoblastic leukemia the association with the hereditary rs924607 polymorphism in the i cep72 i gene |
| topic | vincristine neurotoxicity acute leukemia polyneuropathy genetic variant cep72 |
| url | https://almclinmed.ru/jour/article/viewFile/11753/1571 |
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