Genetic determinants of chemotherapy-induced oral mucositis in children with solid malignancies.
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BACKGROUND: Oral mucositis is a clinically significant side effect of systemic chemotherapy in children with cancer. Understanding its genetic determinants may help develop stratified prophylactic and treatment strategies. However, existing literature primarily focuses on children with hematological malignancies. METHODS: We performed a candidate gene study of 101 children with solid tumors. Clinical data were extracted from the electronic medical record. NCI-CTCAE v6.0 grade ≥2 oral mucositis was defined as the primary outcome. Genetic variants previously associated with oral mucositis were analyzed under an additive genetic model. Exploratory gene-drug interactions were identified based on chemotherapy exposure. RESULTS: Twenty-nine patients (28.7%) developed grade ≥2 oral mucositis. MTHFR rs1801131 (A1298C) was associated with lower odds of grade ≥2 oral mucositis, lower peak mucositis grade, and lower odds of opioid use for oral mucositis in our cohort. Twenty-five exploratory gene-drug interaction signals were identified, including miR-1206 rs2114358 with methotrexate exposure and ABCB1 rs1045642 with anthracycline exposure. CONCLUSIONS: MTHFR rs1801131 (A1298C) was associated with lower odds of chemotherapy-induced oral mucositis in our cohort of children with solid tumors. However, our study was limited by low sample size, and so findings should be considered exploratory. Larger, ancestry-informed studies are required to validate our findings.