Genetic markers for treatment-related pancreatitis in a cohort of Hispanic children with acute lymphoblastic leukemia
| Autor: | Allison Grimes, Jaime Estrada, Yi Chen, Luz N. Perez Prado, Gail E. Tomlinson, Hima Bansal, Gerardo Quezada, Christine Aguilar |
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| Rok vydání: | 2020 |
| Předmět: |
Genetic Markers
Male Oncology Asparaginase medicine.medical_specialty Adolescent Cystic Fibrosis Transmembrane Conductance Regulator Article Cohort Studies 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Humans Genetic Predisposition to Disease 030212 general & internal medicine Child Adverse effect business.industry Hispanic or Latino Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Pediatric cancer Leukemia Pancreatitis chemistry Genetic marker Case-Control Studies Child Preschool 030220 oncology & carcinogenesis Cohort Female Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor business Complication |
| Zdroj: | Support Care Cancer |
| ISSN: | 1433-7339 0941-4355 |
| DOI: | 10.1007/s00520-020-05530-w |
| Popis: | PURPOSE: Treatment-related pancreatitis (TRP) is a serious complication occurring in children with acute lymphoblastic leukemia (ALL). Those affected are at high risk for severe organ toxicity and treatment delays that can impact outcomes. TRP is associated with asparaginase, a standard therapeutic agent in childhood ALL. Native American ancestry, older age, high-risk leukemia, and increased use of asparaginase are linked to pancreatitis risk. However, dedicated genetic studies evaluating pancreatitis in childhood ALL include few Hispanics. Thus, the genetic basis for higher risk of pancreatitis among Hispanic children with ALL remains unknown. METHODS: Cases of children with ALL treated in from 1994 through 2013 were reviewed and identified 14, all Hispanic, who developed pancreatitis related to asparaginase therapy. Forty-six controls consisting of Hispanic children treated on the same regimens without pancreatitis were selected for comparison. Total DNA isolated from whole blood was used for targeted DNA sequencing of 23 selected genes, including genes associated with pancreatitis without ALL and genes involved in asparagine metabolism. RESULTS: Non-synonymous polymorphisms and frameshift deletions were detected in 15 genes. Most children with TRP had variants in ABAT, ASNS, and CFTR. Notably, children with TRP harbored many more CFTR variants (71.4%) compared to controls (39.1%). Among these, V470M (rs213950) was most frequent (OR 4.27, p=0.029). CONCLUSIONS: This is the first study of genetic factors in treatment-related pancreatitis in Hispanic children with ALL. Identifying correlative variants in ethnically vulnerable populations may improve screening to identify which patients with ALL are at greatest risk for pancreatitis. |
| Databáze: | OpenAIRE |
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