Identification of germline polymorphisms associated with clinical and toxicity phenotypes in childhood acute lymphoblastic leukemia

T Bartram; E Ellinghaus; R Houlston; M Zimmermann; A Möricke; G Cario; A Franke; M Schrappe; M Stanulla

doi:10.1055/s-0033-1343635

Identification of germline polymorphisms associated with clinical and toxicity phenotypes in childhood acute lymphoblastic leukemia

T Bartram ¹, E Ellinghaus ², R Houlston ³, M Zimmermann ⁴, A Möricke ¹, G Cario ¹, A Franke ², M Schrappe ¹, M Stanulla ¹

¹Department of Paediatrics, University Hospital Schleswig-Holstein, Kiel
²Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel
³Division of Genetics and Epidemiology, Institute of Cancer Research, Surrey, UK
⁴Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

Abstract

Background: There are many known undesirable side effects during childhood acute lymphoblastic leukemia (ALL) therapy. However, the reasons why some patients suffer from toxicities and others do not remains to be elucidated.

Methods: Genome-wide association analyses of 1,048,683 single nucleotide polymorphisms (SNPs) were conducted in 1489 childhood ALL patients treated on protocol ALL-BFM 2000. Several variables including treatment response and toxicity phenotypes were analyzed.

Results: We were able to detect SNPs with highly significant differences regarding several phenotypes. Many of these are on or close to genes, which can be directly associated with the analyzed phenotype. More detailed information of the individual phenotypes as well as of the validation of candidate SNPs and the conclusions will be presented at the meeting.