DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia
DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia
复制标题
DOI：
10.1007/s13277-016-4908-2
复制
发表时间：
2016-08-01
期刊：
影响因子：
--
通讯作者：
Gao, Xing
中科院分区：
文献类型：
--
作者：
Zhao, Xiao-Qiang;Cao, Wei-Jie;Gao, Xing
我们旨在探讨二氢嘧啶脱氢酶（DPYD）基因多态性与儿童急性淋巴细胞白血病（ALL）风险及其化疗后预后的关系。选取2011年1月至2014年12月在我院诊断的儿科ALL患者147例作为病例组，选取同期在我院体检的健康人群102例作为对照组。应用DNA测序技术对DPYD 85T > C、2194G > A、1156G > T和IVS14 + 1G > A多态性进行位点测定和基因分型。比较两组的基因型和等位基因频率。85T > C多态性的突变基因和等位基因频率与对照组比较差异有统计学意义（P < 0.05）。85T > C多态性中CT和CC基因型与ALL发病风险相关（OR = 1.592, 95% CI = 1.010-2.509），提示隐性基因85C比显性基因85T更容易导致ALL的发生（P < 0.05）。携带85T > C多态性C等位基因的患者肝功能受损程度和感染率高于携带非C等位基因的患者（P < 0.05）。IVS14 + 1G > A多态性中GA基因型患者的肝功能损害比例和感染率高于GG基因型（P < 0.05）。IVS14 + 1G > A多态性的GG基因型患者的完全缓解率（CR）高于GA基因型患者（P = 0.020）。以5-氟尿嘧啶/亚叶酸钙（5-FU/CF）为基础的化疗后，TT基因型患者的无事件生存率（EFS）高于CT和CC基因型患者（P < 0.05）。我们的研究结果表明，85t>c多态性的C等位基因可能与儿童ALL的易感性有关。携带C等位基因的患者患ALL的风险可能会增加。因此，85t>c多态性可能是儿科ALL患者CR的预测因子。
We aimed to investigate the association between dihydropyrimidine dehydrogenase (DPYD) gene polymorphisms and the risk of pediatric acute lymphoblastic leukemia (ALL) and its prognosis after chemotherapy. A total of 147 pediatric ALL patients diagnosed by our hospital between January 2011 and December 2014 were included in the case group, and 102 healthy people who received a physical examination during the same time frame in our hospital were included in the control group. DNA sequencing was applied for site determination and genotyping of the DPYD 85T > C, 2194G > A, 1156G > T, and IVS14 + 1G > A polymorphisms. The genotype and allele frequencies of the two groups were compared. A significant difference was found in the comparison of the mutant gene and allele frequencies of the 85T > C polymorphism between the case and control groups (P < 0.05). The CT and CC genotypes in the 85T > C polymorphism were associated with the risk of the disease (OR = 1.592, 95 % CI = 1.010-2.509), suggesting that the recessive gene (85C) was more likely to lead to the occurrence of ALL compared with the dominant gene (85T) (P < 0.05). Patients carrying the C allele of the 85T > C polymorphism presented higher damage of their liver functions and higher infection rates compared with patients carrying the non-C allele (P < 0.05). A higher proportion of liver function damage and a higher infection rate were found in patients with the GA genotype in the IVS14 + 1G > A polymorphism compared with the GG genotype (P < 0.05). The complete remission (CR) rate in patients with the GG genotype in the IVS14 + 1G > A polymorphism was higher than in patients with the GA genotype (P = 0.020). After 5-fluorouracil/calcium folinate (5-FU/CF)-based chemotherapy, the event-free survival (EFS) rate of patients with the TT genotype was higher than patients with the CT and CC genotypes (P < 0.05). Our results revealed that the C allele of the 85T > C polymorphism might be associated with susceptibility to pediatric ALL. Patients carrying the C allele may have an increased risk of ALL. Thus, the 85T > C polymorphism may be a predictor of CR for pediatric ALL patients.