Nature Communications (Sep 2018)
Exome-wide analysis identifies three low-frequency missense variants associated with pancreatic cancer risk in Chinese populations
- 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,
- Xiating Peng,
- Zhi Zhang,
- Xuemei Zhang,
- Kun Huang,
- Ming Yang,
- Li Wang,
- Chen Wu,
- Dongxin Lin,
- Xiaoping Miao
Affiliations
- Jiang Chang
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Jianbo Tian
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Ying Zhu
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Rong Zhong
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Kan Zhai
- Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Jiaoyuan Li
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Juntao Ke
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- QiangQiang Han
- Wuhan GeneCreate Biological Engineering Co., Ltd
- Jiao Lou
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Wei Chen
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Beibei Zhu
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Na Shen
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Yi Zhang
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Yajie Gong
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Yang Yang
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Danyi Zou
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Xiating Peng
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- Zhi Zhang
- Department of Chemotherapy and Radiotherapy, Tangshan Gongren Hospital
- Xuemei Zhang
- Department of Molecular Genetics, College of Life Science, North China University of Science and Technology
- Kun Huang
- Tongji School of Pharmacy, Huazhong University of Science and Technology
- Ming Yang
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences
- Li Wang
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
- Chen Wu
- Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Dongxin Lin
- Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Xiaoping Miao
- Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology
- DOI
- https://doi.org/10.1038/s41467-018-06136-x
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 8
Abstract
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.
