oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2025-24-3-50-64oncotomsk-3664Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESВарианты генов, которые могут быть связаны с побочными реакциями на лекарственные препараты при лечении неходжкинской лимфомы: геномный и биоинформатический подходGene variants that may cause adverse drug reactions in non-Hodgkin’s lymphoma therapy: a genomic and bioinformatics approachhttps://orcid.org/0009-0004-7767-9979GustinandaR.GustinandaR.

Rizky Gustinanda - фармацевт.

Джокьякарта

Rizky Gustinanda, Pharmacist.

Yogyakarta

https://orcid.org/0000-0002-0091-4887IrhamL. М.IrhamL. M.

Lalu Muhammad Irham - PhD, преподаватель.

Джокьякарта; Накхонпатхом

Lalu Muhammad Irham - PhD, Lecturer.

Yogyakarta, Nakhon

lalu.irham@pharm.uad.ac.idhttps://orcid.org/0000-0003-2033-3905SupadmiW.SupadmiW.

Woro Supadmi - доцент.

Джокьякарта

Woro Supadmi - Associate Professor.

Yogyakarta

https://orcid.org/0000-0002-4256-6534AmuktiD. P.AmuktiD. P.

Danang Prasetyaning Amukti - преподаватель.

Джокьякарта

Danang Prasetyaning Amukti - Pharmacist, Lecturer.

Yogyakarta

https://orcid.org/0000-0001-9165-690XAdikusumaW.AdikusumaW.

Wirawan Adikusuma - PhD, научный сотрудник.

Матарам; Чибинонг

Wirawan Adikusuma - PhD, Researcher.

Cibinong, Mataram

https://orcid.org/0000-0001-6736-9687ChongR.ChongR.

Rockie Chong - PhD.

Лос-Анджелес

Rockie Chong - PhD.

Los Angeles

https://orcid.org/0000-0002-1775-1041KhairR. ElKhairR. El

Riat El Khair - доктор.

Джокьякарта

Riat El Khair - MD.

Yogyakarta

https://orcid.org/0000-0002-7910-4325SatriaR. D.SatriaR. D.

Rahmat Dani Satria - доктор.

Джокьякарта

Rahmat Dani Satria - MD.

Yogyakarta

https://orcid.org/0009-0006-2419-7380WirsahadaR. D.WirsahadaB. C.

Brilliant Citra Wirsahada - доктор.

Сурабая, Восточная Ява

Brilliant Citra Wirsahada - MD.

Jawa Timur

Фармацевтический факультет, Университет Ахмада ДахланаИндонезияFaculty of Pharmacy, Universitas Ahmad DahlanIndonesiaФармацевтический факультет, Университет Ахмада Дахлана; Фармацевтический факультет, Университет СилпакорнИндонезияFaculty of Pharmacy, Universitas Ahmad Dahlan; Faculty of Pharmacy, Silpakorn UniversityIndonesiaКафедра фармации, факультет медицинских наук, Алма-Атинский университетИндонезияDepartment of Pharmacy, Faculty of Health Science, Alma Ata UniversityIndonesiaНаучно-исследовательский центр вычислительной техники, Научно-исследовательская организация по электронике и информатике, Национальное агентство исследований и инноваций (BRIN), Научный центр Чибинонг; Фармацевтический факультет, Университет Мухаммадия МатарамИндонезияResearch Center for Computing, Research Organization for Electronics and Informatics, National Research and Innovation Agency (BRIN), Cibinong Science Center; Department of Pharmacy, Universitas Muhammadiyah MataramIndonesiaКафедра химии и биохимии, Калифорнийский университетСоединённые Штаты АмерикиDepartment of Chemistry and Biochemistry, University of CaliforniaUnited StatesМедицинское отделение, Центральная больница общего профиля доктора СарджитоИндонезияDepartment Medical, Dr. Sardjito Central General HospitalIndonesiaКафедра хирургии медицинского факультета, Университет Мухаммадии СурабаяИндонезияDepartment of Surgery, Faculty of Medicine, Universitas Muhammadiyah SurabayaIndonesia2025040820252435064Copyright © Gustinanda R., Irham L.М., Supadmi W., Amukti D.P., Adikusuma W., Chong R., Khair R.E., Satria R.D., Wirsahada R.D., 20252025Gustinanda R., Irham L.М., Supadmi W., Amukti D.P., Adikusuma W., Chong R., Khair R.E., Satria R.D., Wirsahada R.D.Gustinanda R., Irham L.M., Supadmi W., Amukti D.P., Adikusuma W., Chong R., Khair R.E., Satria R.D., Wirsahada B.C.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/3664Введение

Введение. Химиотерапия остается краеугольным камнем лечения большинства пациентов с неходжкинской лимфомой (НХЛ), однако она часто связана со значительными побочными эффектами. Новые данные подчеркивают, что генетические факторы, в частности однонуклеотидные полиморфизмы (SNP), играют решающую роль в определении индивидуальных различий в ответах на лечение и восприимчивости к побочным эффектам.

Цель исследования – выявление однонуклеотидных полиморфизмов, связанных с нежелательными реакциями на химиотерапию при лечении НХЛ, с использованием современных биоинформатических подходов, позволяющих разрабатывать персонализированные терапевтические стратегии для снижения риска осложнений.

Материал и методы

Материал и методы. В исследовании использовалась база данных PharmGKB для идентификации SNP, связанных с ритуксимабом, циклофосфамидом, доксорубицином, винкристином и преднизоном. SNP, соответствующие критериям включения (уровень доказательности 1A-3, p<0,01), были приоритетными для анализа функционального воздействия с помощью программы PolyPhen-2. Для получения и статистического анализа данных применялись SNPnexus, HaploReg v4.2, Ensembl Genome Browser (GRCh37) и PharmGKB. Методология исследования основывалась на описательном подходе, использовались исключительно вторичные источники данных.

Результаты

Результаты. Выявлено 11 SNP, которые могут ассоциироваться с гематологической токсичностью, повреждением печени и риском тошноты. К ним относятся гены: SLC22A16, GSTP1, NAT2, ATM, ABCB1, CYP2B6, XRCC1, ERCC1, MUTYH, PIK3R2 и PNPLA3. С точки зрения риска возникновения побочных эффектов наиболее значимые варианты – rs738409 (PNPLA3), rs12210538 (SLC22A16), rs2229109 (ABCB1) и rs56022120 (PIK3R2). Аллели SNP более распространены в европейских популяциях по сравнению с азиатскими и африканскими.

Заключение

Заключение. Впервые мы обнаружили SNP, которые указывают на повышенный риск побочных эффектов лекарственной терапии. Эти SNP (rs738409, rs12210538, rs2229109 и rs56022120) усугубляют течение НХЛ во время химиотерапии. Для оценки возможности применения этих биомаркеров в клинической практике для опеределения персонализированной терапии необходима дополнительная клиническая валидация.

Introduction

Introduction. Chemotherapy remains a cornerstone treatment for most non-Hodgkin lymphoma (NHL) patients, yet it is frequently associated with significant adverse effects that compromise their quality of life. Emerging evidence highlights that genetic factors, particularly single nucleotide polymorphisms (SNPs), play a critical role in determining individual variability in treatment responses and susceptibility to drug-related complications.

Aim of this study

Aim of this study: to identify SNPs associated with chemotherapy-induced adverse events in NHL through advanced bioinformatics approaches, enabling personalized therapeutic strategies to mitigate risks.

Material abd Methods

Material abd Methods. This study leveraged the PharmGKB database to identify SNPs associated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. SNPs meeting inclusion criteria (Level of Evidence 1A-3, p<0.01) were prioritized for functional impact analysis using PolyPhen-2 scores. Data extraction and computational analysis utilized SNPnexus, HaploReg v4.2, Ensembl Genome Browser (GRCh37), and PharmGKB. The methodology employed a descriptive approach, relying exclusively on secondary data sources.

Results

Results. This study identified 11 SNPs that may be important for hematological toxicity, liver damage, and nausea risk. These genes are SLC22A16, GSTP1, NAT2, ATM, ABCB1, CYP2B6, XRCC1, ERCC1, MUTYH PIK3R2, and PNPLA3. In terms of priority and risk, the most significant variants were rs738409 (PNPLA3), rs12210538 (SLC22A16), rs2229109 (ABCB1), and rs56022120 (PIK3R2). The distribution of SNP alleles is more common in European populations than in Asians or Africans.

Conclusion

Conclusion. For the first time, we found SNPs that indicate an increase in drug side effects. These SNPs rs738409, rs12210538, rs2229109 and rs56022120 increase the severity of NHL patients during chemotherapy. In order to ensure that these biomarkers can be used in clinical practice and to support the creation of precision medicine strategies, additional clinical validation is needed.

неходжкинская лимфомапобочные реакции на лекарственные препаратыоднонуклеотидный полиморфизмrs738409rs12210538rs2229109rs56022120non-Hodgkin’s lymphomaadverse drug reactionsSNPrs738409rs12210538rs2229109rs56022120Выражаем искреннюю благодарность Управлению исследований и общественных служб (DPPM) Kemdikbudristek за поддержку и финансовую помощь в рамках грантов № 127/PTM/LPPM.UAD/VI и 0419/C3/DT.05.00/2025, благодаря которым это исследование стало возможным в 2025 годуWe would like to express our sincere gratitude to the Directorate of Research and Community Service (DPPM), Kemdikbudristek, for their support and financial assistance through grant numbers 127/PTM/LPPM.UAD/VI and 0419/C3/DT.05.00/2025, which made this research possible in 2025ReferencesSwerdlow S.H., Campo E., Pileri S.A., Harris N.L., Stein H., Siebert R., Advani R., Ghielmini M., Salles G.A., Zelenetz A.D., Jaffe E.S. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. 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The authors declare that there are no conflicts of interest present.