Cell Discovery (Dec 2021)
Genome-wide association and functional interrogation identified a variant at 3p26.1 modulating ovarian cancer survival among Chinese women
- Hongji Dai,
- Xinlei Chu,
- Qian Liang,
- Mengyun Wang,
- Lian Li,
- Yao Zhou,
- Zhanye Zheng,
- Wei Wang,
- Zhao Wang,
- Haixin Li,
- Jianhua Wang,
- Hong Zheng,
- Yanrui Zhao,
- Luyang Liu,
- Hongcheng Yao,
- Menghan Luo,
- Qiong Wang,
- Shan Kang,
- Yan Li,
- Ke Wang,
- Fengju Song,
- Ruoxin Zhang,
- Xiaohua Wu,
- Xi Cheng,
- Wei Zhang,
- Qingyi Wei,
- Mulin Jun Li,
- Kexin Chen
Affiliations
- Hongji Dai
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Xinlei Chu
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Qian Liang
- Department of Pharmacology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University
- Mengyun Wang
- Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University
- Lian Li
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Yao Zhou
- Department of Pharmacology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University
- Zhanye Zheng
- Department of Pharmacology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University
- Wei Wang
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Zhao Wang
- Department of Pharmacology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University
- Haixin Li
- Cancer Biobank, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Jianhua Wang
- Department of Pharmacology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University
- Hong Zheng
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Yanrui Zhao
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Luyang Liu
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Hongcheng Yao
- School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong
- Menghan Luo
- Department of Pharmacology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University
- Qiong Wang
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Shan Kang
- Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital
- Yan Li
- Department of Molecular Biology, Hebei Medical University, Fourth Hospital
- Ke Wang
- Department of Gynecologic Oncology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Fengju Song
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Ruoxin Zhang
- Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University
- Xiaohua Wu
- Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University
- Xi Cheng
- Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University
- Wei Zhang
- Center for Cancer Genomics and Precision Oncology, Wake Forest Baptist Comprehensive Cancer Center, Wake Forest Baptist Medical Center
- Qingyi Wei
- Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University
- Mulin Jun Li
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- Kexin Chen
- Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
- DOI
- https://doi.org/10.1038/s41421-021-00342-6
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 17
Abstract
Abstract Ovarian cancer survival varies considerably among patients, to which germline variation may also contribute in addition to mutational signatures. To identify genetic markers modulating ovarian cancer outcome, we performed a genome-wide association study in 2130 Chinese ovarian cancer patients and found a hitherto unrecognized locus at 3p26.1 to be associated with the overall survival (P combined = 8.90 × 10−10). Subsequent statistical fine-mapping, functional annotation, and eQTL mapping prioritized a likely casual SNP rs9311399 in the non-coding regulatory region. Mechanistically, rs9311399 altered its enhancer activity through an allele-specific transcription factor binding and a long-range interaction with the promoter of a lncRNA BHLHE40-AS1. Deletion of the rs9311399-associated enhancer resulted in expression changes in several oncogenic signaling pathway genes and a decrease in tumor growth. Thus, we have identified a novel genetic locus that is associated with ovarian cancer survival possibly through a long-range gene regulation of oncogenic pathways.
