Department of Hematology & Oncology, University Children's Hospital, Ljubljana, Slovenia.
Leuk Lymphoma. 2009 Oct;50(10):1693-8. doi: 10.1080/10428190903177212.
Anthracyclines have contributed significantly to the increased cure rate in pediatric oncology. Cardiac toxicity is an important late effect after anthracycline treatment and is thought to occur by reactive oxygen species mediated cardiac damage. We hypothesized that deactivating variants of superoxide dismutase II (SOD2) [rs4880 (-9Val > Ala)], catalase (CAT) [rs1001179 (-262C > T) and rs10836235 (c.66 + 78C > T)], GSTT1, and GSTM1 may increase the risk of developing cardiac toxicity, in patients exposed to anthracyclines. The hypothesis was tested in a cohort of 76 long-term survivals of acute lymphoblastic leukemia in childhood. Cardiac damage was evaluated as an attributive variable and compared to gene polymorphisms. In our study group, we show statistically significant correlation between CC homozygosity for CAT (rs10836235 (c.66 + 78C > T)) and cardiac damage after anthracycline exposure (p = 0.020). We found no statistically significant correlation between cardiac damage after anthracycline exposure and deactivating variants of SOD2 [rs4880 (-9Val > Ala)], CAT [rs1001179 (-262C > T), GSTT1, and GSTM1.
蒽环类药物显著提高了儿科肿瘤的治愈率。心脏毒性是蒽环类药物治疗后的一个重要晚期效应，被认为是由活性氧介导的心脏损伤引起的。我们假设，超氧化物歧化酶 II（SOD2）[rs4880（-9Val > Ala）]、过氧化氢酶（CAT）[rs1001179（-262C > T）和 rs10836235（c.66 + 78C > T）]、GSTT1 和 GSTM1 的失活变体可能会增加接受蒽环类药物治疗的患者发生心脏毒性的风险。该假设在儿童急性淋巴细胞白血病的 76 例长期幸存者队列中进行了检验。心脏损伤被评估为一个归因变量，并与基因多态性进行了比较。在我们的研究组中，我们发现 CAT（rs10836235（c.66 + 78C > T））CC 纯合子与蒽环类药物暴露后的心脏损伤之间存在统计学显著相关性（p = 0.020）。我们没有发现蒽环类药物暴露后的心脏损伤与 SOD2 [rs4880（-9Val > Ala）]、CAT [rs1001179（-262C > T）]、GSTT1 和 GSTM1 的失活变体之间存在统计学显著相关性。
