Journal article
Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol
Copenhagen University Hospital Herlev and Gentofte1
Department of Systems Biology, Technical University of Denmark2
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark3
Functional Human Variation, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark4
Department of Bio and Health Informatics, Technical University of Denmark5
Disease Intelligence and Molecular Evolution, Department of Bio and Health Informatics, Technical University of Denmark6
Asparaginase (ASP)-associated pancreatitis (AAP) occurs during acute lymphoblastic leukemia treatment. Among 1285 children (1.0-17.9 years) diagnosed during July 2008-December 2014 and treated according to the Nordic/Baltic ALL2008 protocol, 86 (cumulative incidence = 6.8%) developed AAP. Seventy-three cases were severe (diagnostic AAP criteria persisting 472 h) and 13 mild.
Cases were older than controls (median: 6.5 vs 4.5 years; P = 0.001). Pseudocysts developed in 28%. Of the 20 re-exposed to ASP, 9 (45%) developed a second AAP. After a median follow-up of 2.3 years, 8% needed permanent insulin therapy, and 7% had recurrent abdominal pain. Germline DNA on 62 cases and 638 controls was genotyped on Omni2.5exome-8-v1.2 BeadChip arrays.
Overall, the ULK2 variant rs281366 showed the strongest association with AAP (P = 5.8x10(-7); odds ratio (OR) = 6.7). Cases with the rs281366 variant were younger (4.3 vs 8 years; P = 0.015) and had lower risk of AAP-related complications (15% vs 43%; P = 0.13) compared with cases without this variant.
Among 45 cases and 517 controls
| Language: | English |
|---|---|
| Publisher: | Nature Publishing Group |
| Year: | 2016 |
| Pages: | 325-332 |
| ISSN: | 14765551 and 08876924 |
| Types: | Journal article |
| DOI: | 10.1038/leu.2016.203 |
| ORCIDs: | 0000-0002-3902-3694 and Gupta, R. |
Adolescent Alleles Antineoplastic Agents Asparaginase Biomarkers Case-Control Studies Child Child, Preschool Female Gene Frequency Genetic Association Studies Genotype Humans Infant Male Odds Ratio Pancreatitis Phenotype Polymorphism, Single Nucleotide Precursor Cell Lymphoblastic Leukemia-Lymphoma Protein Serine-Threonine Kinases Severity of Illness Index Ulk2 protein, human
