Trypsin encoding PRSS1-PRSS2 variation influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report.

Trypsin encoding PRSS1-PRSS2 variation influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report. Haematologica. 2018 Nov 22;: Authors: Wolthers BO, Frandsen TL, Patel CJ, Abaji R, Attarbaschi A, Barzilai S, Colombini A, Escherich G, Grosjean M, Krajinovic M, Larsen E, Liang DC, Möricke A, Rasmussen KK, Samarasinghe S, Silverman LB, van der Sluis IM, Stanulla M, Tulstrup M, Yadav R, Yang W, Zapotocka E, Gupta R, Schmiegelow K Abstract Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten acute lymphoblastic leukemia trial groups contributed remission samples from patients aged 1.0-17.9 years and treated from 2000-2016. Cases were defined (n=244) by at least two of the following criteria: i) abdominal pain, ii) pancreatic enzymes >3 x upper normal limit, iii) imaging compatible with asparaginase-associated pancreatitis. Controls (n=1320) completed intended asparaginase therapy, 78% receiving ≥8 pegylated-asparaginase injections, without developing aparaginase-associated pancreatitis. rs62228256 on 20q13.2 showed the strongest association (OR=3.75; P=5.2x10-8). Moreover, rs13228878 (OR=0.61; P=7.1x10-6) and rs10273639 (OR=0.62; P=1.1x10-5) on 7q34 showed significant association...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research