Neuroblastoma(NB)is one of the most common malignant tumors in children,with variable clinical behaviors and a 15%death rate of all malignancies in childhood.However,genetic susceptibility to sporadic NB in Han Chines...Neuroblastoma(NB)is one of the most common malignant tumors in children,with variable clinical behaviors and a 15%death rate of all malignancies in childhood.However,genetic susceptibility to sporadic NB in Han Chinese patients is largely unknown.To identify genetic risk factors for NB,we performed an association study on 357 NB patients and 738 control subjects among Han Chinese children.We focused on DEAD box 1(DDX1),a putative RNA helicase,which is involved in NB carcinogenesis.The potential association of DDX1 polymorphisms with NB has not been discovered.Our results demonstrate that rs72780850(NM_004939.2:c.-1555 T>C)located in the DDX1 promoter region is significantly associated with higher expression of DDX1 transcript and increased NB risk(odds ratio=1.64,95%confidence interval=1.03%–2.60%,P=0.004),especially in aggressive NB compared with ganglioneuroma and ganglioneuroblastoma in a dominant model(TC+CC vs.TT).Furthermore,the MYC-associated protein X(MAX)transcription factor showed stronger binding affinity to the DDX1 rs72780850 CC allele compared with the TT allele,explaining the molecular mechanism of the increased NB risk caused by the rs72780850 polymorphism.Our results highlight the involvement of regulatory genetic variants of DDX1 in NB.展开更多
基金supported by the National Natural Science Foundation of China(81472369 and 81502144)Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education(KZ201810025034)+2 种基金Clinical Application Research Funds of Capital Beijing(Z171100001017051)Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201804 and BHME201904)The Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority(XTCX201806)。
文摘Neuroblastoma(NB)is one of the most common malignant tumors in children,with variable clinical behaviors and a 15%death rate of all malignancies in childhood.However,genetic susceptibility to sporadic NB in Han Chinese patients is largely unknown.To identify genetic risk factors for NB,we performed an association study on 357 NB patients and 738 control subjects among Han Chinese children.We focused on DEAD box 1(DDX1),a putative RNA helicase,which is involved in NB carcinogenesis.The potential association of DDX1 polymorphisms with NB has not been discovered.Our results demonstrate that rs72780850(NM_004939.2:c.-1555 T>C)located in the DDX1 promoter region is significantly associated with higher expression of DDX1 transcript and increased NB risk(odds ratio=1.64,95%confidence interval=1.03%–2.60%,P=0.004),especially in aggressive NB compared with ganglioneuroma and ganglioneuroblastoma in a dominant model(TC+CC vs.TT).Furthermore,the MYC-associated protein X(MAX)transcription factor showed stronger binding affinity to the DDX1 rs72780850 CC allele compared with the TT allele,explaining the molecular mechanism of the increased NB risk caused by the rs72780850 polymorphism.Our results highlight the involvement of regulatory genetic variants of DDX1 in NB.
