Sági Judit C, Gézsi András, Egyed Bálint, Jakab Zsuzsanna, Benedek Noémi, Attarbaschi Andishe, Köhrer Stefan, Sipek Jakub, Winkowska Lucie, Zaliova Marketa, Anastasopoulou Stavroula, Wolthers Benjamin Ole, Ranta Susanna, Szalai Csaba, Kovács Gábor T, Semsei Ágnes F, Erdélyi Dániel J
Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Hungary.
Department of Measurement and Information Systems, Budapest University of Technology and Economics, H-1111 Budapest, Hungary.
Cancers (Basel). 2021 May 12;13(10):2333. doi: 10.3390/cancers13102333.
Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort ( = 107 cases, = 211 controls) but none of the associations could be validated. Overall populations including all nations' matched cohorts for ATE ( = 426) with seizure subgroup ( = 133) and posterior reversible encephalopathy syndrome (PRES, = 251) were analyzed, as well. We found that patients with rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.
尽管儿童急性淋巴细胞白血病（ALL）的治愈率有所提高，但治疗副作用和复发仍是持续存在的挑战。这些情况也可能影响中枢神经系统（CNS）。我们的目的是确定影响中枢神经系统事件风险的种系基因多态性。在匈牙利一个由36例化疗相关急性中毒性脑病（ATE）患者和544例对照组成的非匹配ALL队列中，对20个基因中的60个单核苷酸多态性（SNP）进行了基因分型。在一个扩大的奥地利-捷克-NOPHO队列（107例患者，211例对照）中对5个显著的SNP进行了进一步分析，但没有一个关联能够得到验证。还分析了包括所有国家与ATE匹配队列（426例）的癫痫亚组（133例）和后部可逆性脑病综合征（PRES，251例）的总体人群。我们发现，携带rs1045642、rs1128503或rs2032582 TT基因型的患者更容易发生癫痫，但携带rs1045642 TT基因型的患者发生PRES的频率较低。在一个来自所有组的320例患者的病例对照匹配队列中，还研究了相同的SNP与ALL复发的关系。携带rs1128503 CC或rs2032582 GG基因型的患者中枢神经系统复发的发生率较高。我们的结果表明，血脑屏障药物转运体基因多态性可能与癫痫和中枢神经系统复发呈负相关。
