MYC-associated protein X binding with the variant rs72780850 in RNA helicase DEAD box 1 for susceptibility to neuroblast
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C-associated protein X binding with the variant rs72780850 in RNA helicase DEAD box 1 for susceptibility to neuroblastoma 1†
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Yaqiong Jin , Jin Shi , Huanmin Wang , Jie Lu , Chenghao Chen , Yongbo Yu , Yaru Wang , 1 1 4 1,6,7 1,7* & Yongli Guo Yeran Yang , Dong Ren , Qi Zeng , Xin Ni 1
Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, 2
National Center for Children’s Health, Beijing 100045, China; Department of Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital,
Capital Medical University, Beijing 101149, China; Department of Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health,
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Beijing 100045, China; Department of Thoracic Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 5
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Beijing 100045, China; Department of Allergy, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health,
Beijing 100045, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University & Capital Medical University, 7
Beijing 100083, China; Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China Received June 8, 2020; accepted August 3, 2020; published online September 8, 2020
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.-1555T>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 rs 72780850 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. neuroblastoma, RNA helicase DEAD box 1, susceptibility Citation:
Jin, Y., Shi, J., Wang, H., Lu, J., Chen, C., Yu, Y., Wang, Y., Yang, Y., Ren,
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