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MYC-associated protein X binding with the variant rs72780850 in RNA helicase DEAD box 1 for susceptibility to neuroblastoma

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Abstract

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.

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Acknowledgements

This work was 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), 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 BHME-201904), and The Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority (XTCX201806). The authors are grateful to the members of the Department of Surgery and Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery of Beijing Children’s Hospital for invaluable technical assistance and advice.

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Authors and Affiliations

  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, National Center for Children’s Health, Beijing, 100045, China

    Yaqiong Jin, Jin Shi, Jie Lu, Yongbo Yu, Yeran Yang, Dong Ren, Xin Ni & Yongli Guo

  2. Department of Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China

    Jin Shi

  3. Department of Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China

    Huanmin Wang

  4. Department of Thoracic Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China

    Chenghao Chen & Qi Zeng

  5. Department of Allergy, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China

    Yaru Wang

  6. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University & Capital Medical University, Beijing, 100083, China

    Xin Ni

  7. Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China

    Xin Ni & Yongli Guo

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  1. Yaqiong Jin
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Correspondence to Yongli Guo.

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Jin, Y., Shi, J., Wang, H. et al. MYC-associated protein X binding with the variant rs72780850 in RNA helicase DEAD box 1 for susceptibility to neuroblastoma. Sci. China Life Sci. 64, 991–999 (2021). https://doi.org/10.1007/s11427-020-1784-7

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