Karas-Kuželički Nataša, Mencej-Bedrač Simona, Jazbec Janez, Marc Janja, Mlinarič-Raščan Irena
Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia.
Unit of Oncology and Hematology, University Medical Centre, University Children's Hospital, 1000 Ljubljana, Slovenia.
Exp Ther Med. 2016 Aug;12(2):840-846. doi: 10.3892/etm.2016.3391. Epub 2016 May 25.
Treatment induced non-traumatic osteonecrosis (ON) has been reported increasingly in children treated for acute lymphoblastic leukemia (ALL). Several risk factors for ON have been identified in childhood cancer patients; however, their diagnostic and prognostic power is limited and the etiology of the disease remains unclear. Therefore, a continuous effort is focused on the identification of additional ON risk factors. We performed a retrospective study of 313 childhood ALL patients to test the association between the ON occurrence in children receiving ALL therapy and common polymorphisms in potential target genes: Thiopurine S-methyltransferase (; 460G>A, 719A>G), 5,10-methylenetetrahydrofolate reductase (; 677C>T, 1298A>C), estrogen receptor alpha 1 (; XbaI) and collagen type I, α1 (; Sp1). In the present cohort, higher age and more recently developed treatment protocols were independent risk factors for ON. In children >14.5 years old, genotype modulated the risk of ON. Additionally, in children <12.9 years old genotypes were also implicated in the pathogenesis of ON. Besides greater age and more recent treatment protocols, genetic factors (polymorphisms in and genes) were suggested to be implicated in the pathogenesis of ON and could be potentially used as genetic prognostic markers for ON.
治疗引起的非创伤性骨坏死（ON）在接受急性淋巴细胞白血病（ALL）治疗的儿童中报告越来越多。在儿童癌症患者中已确定了几种ON的危险因素；然而，它们的诊断和预后能力有限，疾病的病因仍不清楚。因此，持续努力集中在识别更多的ON危险因素上。我们对313例儿童ALL患者进行了一项回顾性研究，以测试接受ALL治疗的儿童中ON的发生与潜在靶基因常见多态性之间的关联：硫嘌呤S-甲基转移酶（；460G>A，719A>G）、5,10-亚甲基四氢叶酸还原酶（；677C>T，1298A>C）、雌激素受体α1（；XbaI）和I型胶原α1（；Sp1）。在本队列中，年龄较大和最近制定的治疗方案是ON的独立危险因素。在年龄>14.5岁的儿童中，基因型调节ON的风险。此外，在年龄<12.9岁的儿童中，基因型也与ON的发病机制有关。除了年龄较大和最近的治疗方案外，遗传因素（和基因中的多态性）被认为与ON的发病机制有关，并可能潜在地用作ON的遗传预后标志物。
