Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis

Aim. To assess the association between the carriage of minor allelic variants of 8 genes that encode key enzymes involved in the metabolism of anticancer drugs (DPYD, GSTP1, MTHFR, UGT1A1) and cell repair (XPC, ERCC1, TYMP, NQO1) and the severity of adverse drug events in patients with common gastro...

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Autores principales:	Denis S. Fedorinov, Rustam N. Geidarov, Igor A. Shashkov, Vladimir M. Mikhailovich, Marina A. Lyadova, Ilya A. Pokataev, Vladimir K. Lyadov
Formato:	article
Lenguaje:	RU
Publicado:	IP Habib O.N. 2021
Materias:	cytotoxic therapy gastrointestinal tract tumors pharmacogenetics biological microchip Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/967f135a4f9d43188148f60682a5b165
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spelling	oai:doaj.org-article:967f135a4f9d43188148f60682a5b1652021-11-30T16:55:01ZPharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis1815-14341815-144210.26442/18151434.2021.2.200890https://doaj.org/article/967f135a4f9d43188148f60682a5b1652021-08-01T00:00:00Zhttps://modernonco.orscience.ru/1815-1434/article/viewFile/75937/pdfhttps://doaj.org/toc/1815-1434https://doaj.org/toc/1815-1442Aim. To assess the association between the carriage of minor allelic variants of 8 genes that encode key enzymes involved in the metabolism of anticancer drugs (DPYD, GSTP1, MTHFR, UGT1A1) and cell repair (XPC, ERCC1, TYMP, NQO1) and the severity of adverse drug events in patients with common gastrointestinal tumors. Tasks. To study the frequency of minor allelic variants of the DPYD, GSTP1, MTHFR, UGT1A1, XPC, ERCC1, TYMP, NQO1 genes; to assess the frequency and severity of adverse drug events of chemotherapy treatment in the study population. Materials and methods. For the period from October 2020 to April 2021, 56 patients (women 29, men 27) with verified malignant tumors of the gastrointestinal tract were included in a prospective clinical study as a part of the RSF grant No. 20-75-10158. The mean age was 62.311.4 years. Colon cancer was detected in 24 patients, tumors of the esophagus and stomach in 19 patients, tumors of pancreas and biliary tract in 13 patients. First-line palliative chemotherapy was given to 27 patients, adjuvant 19 patients, neoadjuvant 10 patients. All patients had not previously received cytotoxic or radiation treatment. Point nucleotide variants of genes DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, TYMPS, NQO1 were determined by hybridization analysis on biological microchips. Differences in the tolerance of cytotoxic therapy (5-fluorouracil, platinum preparations, irinotecan) depending on the genotype were assessed using Fishers exact test. Results. The average number of chemotherapy courses received was 4.22.6 (112). There was a statistically significant difference in the tolerability of chemotherapy in patients with minor allelic variants of the GSTP1 rs1695 (p=0.03), ERCC1 rs11615 (p=0.01), and UGT1A1 rs8175347 (p=0.003) genes. Conclusion. The use of hybridization analysis on biological microchips to assess allelic variants responsible for the tolerability of cytotoxic therapy is reasonable and requires further prospective assessment.Denis S. FedorinovRustam N. GeidarovIgor A. ShashkovVladimir M. MikhailovichMarina A. LyadovaIlya A. PokataevVladimir K. LyadovIP Habib O.N.articlecytotoxic therapygastrointestinal tract tumorspharmacogeneticsbiological microchipNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282RUСовременная онкология, Vol 23, Iss 2, Pp 314-318 (2021)
institution	DOAJ
collection	DOAJ
language	RU
topic	cytotoxic therapy gastrointestinal tract tumors pharmacogenetics biological microchip Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cytotoxic therapy gastrointestinal tract tumors pharmacogenetics biological microchip Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Denis S. Fedorinov Rustam N. Geidarov Igor A. Shashkov Vladimir M. Mikhailovich Marina A. Lyadova Ilya A. Pokataev Vladimir K. Lyadov Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis
description	Aim. To assess the association between the carriage of minor allelic variants of 8 genes that encode key enzymes involved in the metabolism of anticancer drugs (DPYD, GSTP1, MTHFR, UGT1A1) and cell repair (XPC, ERCC1, TYMP, NQO1) and the severity of adverse drug events in patients with common gastrointestinal tumors. Tasks. To study the frequency of minor allelic variants of the DPYD, GSTP1, MTHFR, UGT1A1, XPC, ERCC1, TYMP, NQO1 genes; to assess the frequency and severity of adverse drug events of chemotherapy treatment in the study population. Materials and methods. For the period from October 2020 to April 2021, 56 patients (women 29, men 27) with verified malignant tumors of the gastrointestinal tract were included in a prospective clinical study as a part of the RSF grant No. 20-75-10158. The mean age was 62.311.4 years. Colon cancer was detected in 24 patients, tumors of the esophagus and stomach in 19 patients, tumors of pancreas and biliary tract in 13 patients. First-line palliative chemotherapy was given to 27 patients, adjuvant 19 patients, neoadjuvant 10 patients. All patients had not previously received cytotoxic or radiation treatment. Point nucleotide variants of genes DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, TYMPS, NQO1 were determined by hybridization analysis on biological microchips. Differences in the tolerance of cytotoxic therapy (5-fluorouracil, platinum preparations, irinotecan) depending on the genotype were assessed using Fishers exact test. Results. The average number of chemotherapy courses received was 4.22.6 (112). There was a statistically significant difference in the tolerability of chemotherapy in patients with minor allelic variants of the GSTP1 rs1695 (p=0.03), ERCC1 rs11615 (p=0.01), and UGT1A1 rs8175347 (p=0.003) genes. Conclusion. The use of hybridization analysis on biological microchips to assess allelic variants responsible for the tolerability of cytotoxic therapy is reasonable and requires further prospective assessment.
format	article
author	Denis S. Fedorinov Rustam N. Geidarov Igor A. Shashkov Vladimir M. Mikhailovich Marina A. Lyadova Ilya A. Pokataev Vladimir K. Lyadov
author_facet	Denis S. Fedorinov Rustam N. Geidarov Igor A. Shashkov Vladimir M. Mikhailovich Marina A. Lyadova Ilya A. Pokataev Vladimir K. Lyadov
author_sort	Denis S. Fedorinov
title	Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis
title_short	Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis
title_full	Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis
title_fullStr	Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis
title_full_unstemmed	Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis
title_sort	pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis
publisher	IP Habib O.N.
publishDate	2021
url	https://doaj.org/article/967f135a4f9d43188148f60682a5b165
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Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis

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