Email this article Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis
- Authors: Fedorinov D.S.1,2, Geidarov R.N.3, Shashkov I.A.3, Mikhailovich V.M.3, Lyadova M.A.2, Pokataev I.A.2, Lyadov V.K.1,2,4
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Affiliations:
- Russian Medical Academy of Continuous Professional Education
- City Clinical Cancer Hospital №1
- Engelhardt Institute of Molecular Biology
- Novokuznetsk State Institute of Postgraduate Medical Education – branch of Russian Medical Academy of Continuous Professional Education
- Issue: Vol 23, No 2 (2021)
- Pages: 314-318
- Section: CLINICAL ONCOLOGY
- URL: https://journals.rcsi.science/1815-1434/article/view/75937
- DOI: https://doi.org/10.26442/18151434.2021.2.200890
- ID: 75937
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Abstract
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 62.3±11.4 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 Fisher’s exact test.
Results. The average number of chemotherapy courses received was 4.2±2.6 (1–12). 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.
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##article.viewOnOriginalSite##About the authors
Denis S. Fedorinov
Russian Medical Academy of Continuous Professional Education; City Clinical Cancer Hospital №1
Author for correspondence.
Email: Fedorinov.denis@gmail.com
ORCID iD: 0000-0001-5516-7367
Senior laboratory assistant
Russian Federation, Moscow; MoscowRustam N. Geidarov
Engelhardt Institute of Molecular Biology
Email: Fedorinov.denis@gmail.com
ORCID iD: 0000-0002-4971-2629
Senior laboratory assistant
Russian Federation, MoscowIgor A. Shashkov
Engelhardt Institute of Molecular Biology
Email: Fedorinov.denis@gmail.com
ORCID iD: 0000-0001-6037-730X
Cand. Sci. (Chem.)
Russian Federation, MoscowVladimir M. Mikhailovich
Engelhardt Institute of Molecular Biology
Email: Fedorinov.denis@gmail.com
ORCID iD: 0000-0003-4894-1304
D. Sci. (Biol.)
Russian Federation, MoscowMarina A. Lyadova
City Clinical Cancer Hospital №1
Email: dr.lyadova@gmail.com
ORCID iD: 0000-0002-9558-5579
Cand. Sci. (Med.)
Russian Federation, MoscowIlya A. Pokataev
City Clinical Cancer Hospital №1
Email: Fedorinov.denis@gmail.com
ORCID iD: 0000-0001-9864-3837
D. Sci. (Med.)
Russian Federation, MoscowVladimir K. Lyadov
Russian Medical Academy of Continuous Professional Education; City Clinical Cancer Hospital №1; Novokuznetsk State Institute of Postgraduate Medical Education – branch of Russian Medical Academy of Continuous Professional Education
Email: vlyadov@gmail.com
ORCID iD: 0000-0002-7281-3591
D. Sci. (Med.)
Russian Federation, Moscow; Moscow; NovokuznetskReferences
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