{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:03:34Z","timestamp":1784527414813,"version":"3.55.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chemotherapy-related toxicities remain a major barrier to optimal outcomes in pediatric cancer care in low-resource settings. Genetic variation in drug-metabolizing and transport pathways contributes to interindividual differences in toxicity risk; however, pharmacogenomic data from African pediatric populations are limited. This study assessed the distribution of selected pharmacogenomic variants and chemotherapy-related toxicities profiles in Tanzanian children with cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cross-sectional study was conducted among 155 pediatric patients with cancer (1\u201317 years) receiving chemotherapy at Bugando Medical Centre, Tanzania. Clinical data, clinician-reported toxicities, and patient-reported outcomes were collected. Eleven pharmacogenomic variants in genes involved in drug metabolism, transport, and detoxification pathways\n                      <jats:italic>(CYP3A5, SLC19A1, TPMT, NUDT15, GSTP1, NCF4, CYBA,<\/jats:italic>\n                      and\n                      <jats:italic>CEP72),<\/jats:italic>\n                      selected based on prior evidence of functional relevance and reported associations with chemotherapy response, were genotyped using the Agena MassARRAY\u00ae platform. Toxicities were graded using CTCAE version 5.0.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hematologic toxicities, including anemia (50.3%) and leukopenia (37.4%), and mucocutaneous toxicities such as alopecia (38.1%) and oral ulcers (24.5%) were common. Reduced muscle strength was observed in 78.1% of patients. Reduced-function\n                      <jats:italic>CYP3A5<\/jats:italic>\n                      variants were frequent (CYP3A5*6: 38.1%; CYP3A5*3: 27.7%). Variants in\n                      <jats:italic>GSTP1<\/jats:italic>\n                      rs1695 (MAF 0.46),\n                      <jats:italic>CYBA<\/jats:italic>\n                      rs4673 (MAF 0.44), and\n                      <jats:italic>SLC19A1<\/jats:italic>\n                      rs1051296 (MAF 0.49) demonstrated substantial variability, indicating potential interindividual differences in drug metabolism and transport. However, no genotype\u2013toxicity associations were assessed in this study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides baseline data on pharmacogenomic variability among Tanzanian pediatric patients with cancer. The observed genetic diversity in pharmacogenes involved in drug metabolism and transport may be relevant to variability in chemotherapy-related toxicities, as reported in previous studies. These findings highlight the need for further research to evaluate genotype\u2013toxicity relationships and to inform the future integration of pharmacogenomics into pediatric oncology care in resource-limited settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1886874","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:34:29Z","timestamp":1784525669000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacogenomic variation and chemotherapy-related toxicity profiles in pediatric patients with cancer in Tanzania: a cross-sectional study"],"prefix":"10.3389","volume":"17","author":[{"given":"Deogratias M.","family":"Katabalo","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy, Catholic University of Health and Allied Sciences","place":["Mwanza, Tanzania"]},{"name":"Department of Oncology, Bugando Medical Centre","place":["Mwanza, Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baraka","family":"Fundo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy, Catholic University of Health and Allied Sciences","place":["Mwanza, Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfrida V.","family":"Minja","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy, Catholic University of Health and Allied Sciences","place":["Mwanza, Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heronima Joas","family":"Kashaigiri","sequence":"additional","affiliation":[{"name":"Department of Oncology, Bugando Medical Centre","place":["Mwanza, Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Mwita","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy, Catholic University of Health and Allied Sciences","place":["Mwanza, Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony Cuthbert","family":"Liwa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Catholic University of Health and Allied Sciences","place":["Mwanza, Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Department of Oncology, Bugando Medical Centre","place":["Mwanza, Tanzania"]},{"name":"Duke University Health Institute","place":["Raleigh, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benson R.","family":"Kidenya","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Catholic University of Health and Allied Sciences","place":["Mwanza, Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.4274\/jpr.galenos.2021.35492","article-title":"Thiopurine-S-Methyltransferase gene polymorphism and drug-related toxicity in children treated for acute leukemia and non-hodgkin\u2019s lymphoma","volume":"9","author":"Ataseven","year":"2022","journal-title":"J. Pediatr. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s10555-020-09859-w","article-title":"Cardiovascular diseases in survivors of childhood cancer","volume":"39","author":"Bansal","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"B3","first-page":"63","article-title":"Pharmacogenomics of drug-metabolizing enzymes and drug transporters in chemotherapy","volume-title":"Pharmacogenomics in Drug Discovery and Development Methods in Molecular Biology","author":"Bosch","year":"2008"},{"key":"B4","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.clinthera.2015.10.017","article-title":"Severe vincristine-induced neuropathic pain in a CYP3A5 nonexpressor with reduced CYP3A4\/5 activity: case study","volume":"38","author":"Bosilkovska","year":"2016","journal-title":"Clin. Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1634\/theoncologist.2012-0239","article-title":"Association of anthracycline-related cardiac histological lesions with NADPH oxidase functional polymorphisms","volume":"18","author":"Cascales","year":"2013","journal-title":"Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"449","DOI":"10.2217\/pgs-2023-0026","article-title":"Pharmacogenetics of 6-Mercaptopurine in a black Zimbabwean cohort treated for acute lymphoblastic leukaemia","volume":"24","author":"Chikondowa","year":"2023","journal-title":"Pharmacogenomics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"42","DOI":"10.4103\/0971-5851.177015","article-title":"Chemotherapy-induced adverse drug reactions in oncology patients: a prospective observational survey","volume":"37","author":"Chopra","year":"2016","journal-title":"Indian J. Med. Paediatr. Oncol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4599","DOI":"10.1007\/s00277-024-05973-9","article-title":"An inherited genetic variant of the CEP72 gene is associated with the development of vincristine-induced peripheral neuropathy in female patients with aggressive B-cell lymphoma","volume":"103","author":"Christofyllakis","year":"2024","journal-title":"Ann. Hematol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12885-025-15384-2","article-title":"Prevalence and factors associated with chemotherapy-induced adverse events in cancer treatment centers in amhara national regional state comprehensive referral hospitals, 2024: multicenter prospective follow up study","volume":"26","author":"Demilie","year":"2025","journal-title":"BMC Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1001\/jama.2015.0894","article-title":"Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia","volume":"313","author":"Diouf","year":"2015","journal-title":"JAMA"},{"key":"B11","doi-asserted-by":"publisher","first-page":"396","DOI":"10.12688\/f1000research.110079.1","article-title":"Drug utilization pattern and adverse drug reactions of chemotherapy in pediatric patients at muhimbili national hospital, Tanzania","volume":"11","author":"Efraim","year":"2022","journal-title":"F1000Research"},{"key":"B12","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1002\/pbc.22845","article-title":"Increased risk of vincristine neurotoxicity associated with low CYP3A5 expression genotype in children with acute lymphoblastic leukemia","volume":"56","author":"Egbelakin","year":"2011","journal-title":"Pediatr. Blood Cancer"},{"key":"B13","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s00280-018-3525-8","article-title":"Role of TPMT and ITPA variants in mercaptopurine disposition","volume":"81","author":"Gerbek","year":"2018","journal-title":"Cancer Chemother. Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1007\/s12032-014-0204-4","article-title":"SLC19A1 hot spot for MTX plasma concentration","volume":"31","author":"Gutierrez-Camino","year":"2014","journal-title":"Med. Oncol."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.01.24314736","article-title":"Comprehensive systematic review and meta-analysis of solute carrier family 19, member 1 (SLC19A1) G80A gene polymorphism and its association with congenital heart defects in fetal development: implications for genetic susceptibility and prenatal risk assessment","author":"Hernandez","year":"2024","journal-title":"Genet. Genomic Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"40","DOI":"10.3390\/jpm9030040","article-title":"Pharmacogenomic testing: clinical evidence and implementation challenges","volume":"9","author":"Hippman","year":"2019","journal-title":"J. Pers. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1186\/s12885-022-10434-5","article-title":"Pharmacogenetics of chemotherapy treatment response and-toxicities in patients with osteosarcoma: a systematic review","volume":"22","author":"Hurkmans","year":"2022","journal-title":"BMC Cancer"},{"key":"B18","volume-title":"Ped-PRO-CTCAE\/Ped-PRO-CTCAE [Caregiver] Instrument and Form Builder","year":"2025"},{"key":"B19","doi-asserted-by":"publisher","first-page":"783","DOI":"10.3390\/jpm11080783","article-title":"TPMT*3C as a predictor of 6-Mercaptopurine-Induced myelotoxicity in Thai children with acute lymphoblastic leukemia","volume":"11","author":"Jantararoungtong","year":"2021","journal-title":"J. Pers. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s44276-024-00064-8","article-title":"New light on chemotherapy toxicity and its prevention","volume":"2","author":"Juthani","year":"2024","journal-title":"BJC Rep."},{"key":"B21","doi-asserted-by":"publisher","first-page":"11537","DOI":"10.3390\/cimb46100685","article-title":"Association of SLC19A1 gene polymorphisms and its regulatory miRNAs with methotrexate toxicity in children with acute lymphoblastic leukemia","volume":"46","author":"Karpa","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1444565","DOI":"10.3389\/fonc.2025.1444565","article-title":"Prescription patterns of supportive care medications among children receiving chemotherapy treatments at a major referral hospital in Tanzania: where are we in managing chemotherapy-induced toxicities?","volume":"15","author":"Katabalo","year":"","journal-title":"Front. Oncol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"55","DOI":"10.2147\/PGPM.S502355","article-title":"Pharmacogenomics of chemotherapies for childhood cancers in Africa: a scoping review","volume":"18","author":"Katabalo","year":"","journal-title":"Pharmacogenomics Pers. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3390\/ph15040439","article-title":"Association between genetic polymorphism of GSTP1 and toxicities in patients receiving platinum-based chemotherapy: a systematic review and meta-analysis","volume":"15","author":"Kim","year":"2022","journal-title":"Pharmaceuticals"},{"key":"B25","doi-asserted-by":"publisher","first-page":"9205","DOI":"10.3390\/curroncol30100665","article-title":"Toxicities and quality of life during cancer treatment in advanced solid tumors","volume":"30","author":"Lee","year":"2023","journal-title":"Curr. Oncol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1093\/toxsci\/kfu162","article-title":"SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients","volume":"142","author":"Lima","year":"2014","journal-title":"Toxicol. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1200\/GO.20.00407","article-title":"Delays experienced by patients with pediatric cancer during the health facility referral process: a study in northern Tanzania","volume":"6","author":"Maillie","year":"2020","journal-title":"JCO Glob. Oncol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e2200263","DOI":"10.1200\/GO.22.00263","article-title":"Childhood and adolescent cancer care at a tertiary hospital in northern Tanzania: a retrospective study","volume":"9","author":"Majaliwa","year":"2023","journal-title":"JCO Glob. Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/1756-0500-7-195","article-title":"Pattern and factors associated with congenital anomalies among young infants admitted at bugando medical centre, Mwanza, Tanzania","volume":"7","author":"Mashuda","year":"2014","journal-title":"BMC Res. Notes"},{"key":"B30","doi-asserted-by":"publisher","first-page":"651720","DOI":"10.3389\/fphar.2021.651720","article-title":"Role of pharmacogenetics in adverse drug reactions: an update towards personalized medicine","volume":"12","author":"Micaglio","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.3390\/ijms17091502","article-title":"Pharmacogenomics in pediatric oncology: review of gene\u2014drug associations for clinical use","volume":"17","author":"Mlakar","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e124","DOI":"10.7759\/cureus.124","article-title":"Chemotherapy-induced peripheral neuropathy in pediatric cancer patients","volume":"5","author":"Moore","year":"2013","journal-title":"Cureus"},{"key":"B33","first-page":"2416","article-title":"Vincristine-induced peripheral neuropathy in pediatric cancer patients","volume":"6","author":"Mora","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/ng.3508","article-title":"NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity","volume":"48","author":"Moriyama","year":"2016","journal-title":"Nat. Genet."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2333794X19849749","DOI":"10.1177\/2333794X19849749","article-title":"Presentation and outcomes of childhood cancer patients at Uganda cancer institute","volume":"6","author":"Mutyaba","year":"2019","journal-title":"Glob. Pediatr. Health"},{"key":"B36","unstructured":"2025"},{"key":"B37","doi-asserted-by":"publisher","first-page":"122","DOI":"10.4103\/ijd.IJD_129_17","article-title":"Mucocutaneous adverse reactions of cancer chemotherapy and chemoradiation","volume":"64","author":"Naveed","year":"2019","journal-title":"Indian J. Dermatol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.4102\/hsag.v25i0.1382","article-title":"Childhood cancers in a section of the South African private health sector: analysis of medicines claims data","volume":"25","author":"Otoo","year":"2020","journal-title":"Health SA Gesondheid"},{"key":"B39","doi-asserted-by":"publisher","first-page":"25355","DOI":"10.18632\/oncotarget.25256","article-title":"SNPs in predicting clinical efficacy and toxicity of chemotherapy: walking through the quicksand","volume":"9","author":"Palmirotta","year":"2018","journal-title":"Oncotarget"},{"key":"B40","doi-asserted-by":"publisher","first-page":"710","DOI":"10.3390\/nu15030710","article-title":"Role of nutrition in pediatric patients with cancer","volume":"15","author":"Pedretti","year":"2023","journal-title":"Nutrients"},{"key":"B41","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/S1470-2045(23)00072-4","article-title":"Access to essential cancer medicines for children: a comparative mixed-methods analysis of availability, price, and health-system determinants in East Africa","volume":"24","author":"Petricca","year":"2023","journal-title":"Lancet Oncol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/clpt.2010.320","article-title":"Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing","volume":"89","author":"Relling","year":"2011","journal-title":"Clin. Pharmacol. Ther."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1002\/cpt.1304","article-title":"Clinical pharmacogenetics implementation consortium guideline for thiopurine dosing based on TPMT and NUDT 15 genotypes: 2018 update","volume":"105","author":"Relling","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"B44","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1200\/GO.22.57000","article-title":"Community awareness about pediatric cancer in Tanzania","volume":"8","author":"Sanga","year":"2022","journal-title":"JCO Glob. Oncol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/JGO.2016.009027","article-title":"Pediatric cancer in northern Tanzania: evaluation of diagnosis, treatment, and outcomes","volume":"4","author":"Schroeder","year":"2017","journal-title":"J. Glob. Oncol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.31557\/APJCP.2024.25.4.1391","article-title":"Efficacy and toxicity of vincristine and cyp3a5 genetic polymorphism in rhabdomyosarcoma pediatric egyptian patients","volume":"25","author":"Shalaby","year":"2024","journal-title":"Asian Pac J. Cancer Prev. APJCP"},{"key":"B47","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s41182-025-00760-2","article-title":"Clinical characteristics and outcomes of paediatric acute lymphoblastic leukaemia in a tertiary hospital in Tanzania: a single-centre observational study","volume":"53","author":"Shimizu","year":"2025","journal-title":"Trop. Med. Health"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1015746","DOI":"10.3389\/fmolb.2022.1015746","article-title":"Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients","volume":"9","author":"Tay","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s12887-023-03891-9","article-title":"Adverse drug events and contributing factors among pediatric cancer patients at jimma university medical center, southwest Ethiopia","volume":"23","author":"Tola","year":"2023","journal-title":"BMC Pediatr."},{"key":"B50","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/wsbm.42","article-title":"Pharmacogenomics: a systems approach","volume":"2","author":"Wang","year":"2010","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1007\/s12032-014-0062-0","article-title":"Effects of a microRNA binding site polymorphism in SLC19A1 on methotrexate concentrations in Chinese children with acute lymphoblastic leukemia","volume":"31","author":"Wang","year":"2014","journal-title":"Med. Oncol."},{"key":"B52","volume-title":"Statistics: An Introductory Analysis","author":"Yamane","year":"1967"},{"key":"B53","doi-asserted-by":"publisher","first-page":"651269","DOI":"10.3389\/fcvm.2021.651269","article-title":"Potential gene association studies of chemotherapy-induced cardiotoxicity: a systematic review and meta-analysis","volume":"8","author":"Yang","year":"2021","journal-title":"Front. Cardiovasc Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"13575","DOI":"10.18632\/oncotarget.14594","article-title":"Impact of NUDT15 polymorphisms on thiopurines-induced myelotoxicity and thiopurines tolerance dose","volume":"8","author":"Yin","year":"2017","journal-title":"Oncotarget"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1886874\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:34:32Z","timestamp":1784525672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1886874\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":54,"alternative-id":["10.3389\/fphar.2026.1886874"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1886874","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"article-number":"1886874"}}