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Exome-wide analysis identifies three low-frequency missense variants associated with pancreatic cancer risk in Chinese populations

Author

Listed:
  • Jiang Chang

    (Huazhong University of Sciences and Technology)

  • Jianbo Tian

    (Huazhong University of Sciences and Technology)

  • Ying Zhu

    (Huazhong University of Sciences and Technology)

  • Rong Zhong

    (Huazhong University of Sciences and Technology)

  • Kan Zhai

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Capital Medical University)

  • Jiaoyuan Li

    (Huazhong University of Sciences and Technology)

  • Juntao Ke

    (Huazhong University of Sciences and Technology)

  • QiangQiang Han

    (Wuhan GeneCreate Biological Engineering Co., Ltd)

  • Jiao Lou

    (Huazhong University of Sciences and Technology)

  • Wei Chen

    (Huazhong University of Sciences and Technology)

  • Beibei Zhu

    (Huazhong University of Sciences and Technology)

  • Na Shen

    (Huazhong University of Sciences and Technology)

  • Yi Zhang

    (Huazhong University of Sciences and Technology)

  • Yajie Gong

    (Huazhong University of Sciences and Technology)

  • Yang Yang

    (Huazhong University of Sciences and Technology)

  • Danyi Zou

    (Huazhong University of Sciences and Technology)

  • Xiating Peng

    (Huazhong University of Sciences and Technology)

  • Zhi Zhang

    (Tangshan Gongren Hospital)

  • Xuemei Zhang

    (North China University of Science and Technology)

  • Kun Huang

    (Huazhong University of Science and Technology)

  • Ming Yang

    (Shandong Academy of Medical Sciences)

  • Li Wang

    (Peking Union Medical College)

  • Chen Wu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Dongxin Lin

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xiaoping Miao

    (Huazhong University of Sciences and Technology)

Abstract

Germline coding variants have not been systematically investigated for pancreatic ductal adenocarcinoma (PDAC). Here we report an exome-wide investigation using the Illumina Human Exome Beadchip with 943 PDAC cases and 3908 controls in the Chinese population, followed by two independent replicate samples including 2142 cases and 4697 controls. We identify three low-frequency missense variants associated with the PDAC risk: rs34309238 in PKN1 (OR = 1.77, 95% CI: 1.48–2.12, P = 5.35 × 10−10), rs2242241 in DOK2 (OR = 1.85, 95% CI: 1.50–2.27, P = 4.34 × 10−9), and rs183117027 in APOB (OR = 2.34, 95% CI: 1.72–3.16, P = 4.21 × 10−8). Functional analyses show that the PKN1 rs34309238 variant significantly increases the level of phosphorylated PKN1 and thus enhances PDAC cells' proliferation by phosphorylating and activating the FAK/PI3K/AKT pathway. These findings highlight the significance of coding variants in the development of PDAC and provide more insights into the prevention of this disease.

Suggested Citation

  • Jiang Chang & Jianbo Tian & Ying Zhu & Rong Zhong & Kan Zhai & Jiaoyuan Li & Juntao Ke & QiangQiang Han & Jiao Lou & Wei Chen & Beibei Zhu & Na Shen & Yi Zhang & Yajie Gong & Yang Yang & Danyi Zou & X, 2018. "Exome-wide analysis identifies three low-frequency missense variants associated with pancreatic cancer risk in Chinese populations," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06136-x
    DOI: 10.1038/s41467-018-06136-x
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