Pharmacogenomic variation and chemotherapy-related toxicity profiles in pediatric patients with cancer in Tanzania: a cross-sectional study.
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BACKGROUND: 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. METHODS: A cross-sectional study was conducted among 155 pediatric patients with cancer (1-17 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 (CYP3A5, SLC19A1, TPMT, NUDT15, GSTP1, NCF4, CYBA, and CEP72), selected based on prior evidence of functional relevance and reported associations with chemotherapy response, were genotyped using the Agena MassARRAY® platform. Toxicities were graded using CTCAE version 5.0. RESULTS: 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 CYP3A5 variants were frequent (CYP3A5*6: 38.1%; CYP3A5*3: 27.7%). Variants in GSTP1 rs1695 (MAF 0.46), CYBA rs4673 (MAF 0.44), and SLC19A1 rs1051296 (MAF 0.49) demonstrated substantial variability, indicating potential interindividual differences in drug metabolism and transport. However, no genotype-toxicity associations were assessed in this study. CONCLUSION: 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-toxicity relationships and to inform the future integration of pharmacogenomics into pediatric oncology care in resource-limited settings.