Oncotarget

Research Papers:

Genome-wide association study identifies two new susceptibility loci for colorectal cancer at 5q23.3 and 17q12 in Han Chinese

Kewei Jiang _, Yimin Sun, Cheng Wang, Jiafu Ji, Yaoping Li, Yingjiang Ye, Liang Lv, Yong Guo, Sutang Guo, Hai Li, Lianhai Zhang, Yanbing Zhou, Bo Jiang, Yonghong Ren, Youchun Xu, Xiongfei Yang, Hongxia Liu, Yirui Wang, Zhanlong Shen, Wenyan Qin, Peng Guo, Yuyang Jiang, Zhibin Hu, Hongbing Shen, Jing Cheng, Yinxue Yang and Shan Wang

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Oncotarget. 2015; 6:40327-40336. https://doi.org/10.18632/oncotarget.5530

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Abstract

Kewei Jiang1,*, Yimin Sun2,3,4,*, Cheng Wang5,6,7,*, Jiafu Ji8,*, Yaoping Li9,10,*, Yingjiang Ye1,*, Liang Lv1,11, Yong Guo12, Sutang Guo10,13, Hai Li14, Lianhai Zhang8, Yanbing Zhou11, Bo Jiang9, Yonghong Ren2, Youchun Xu12, Xiongfei Yang15, Hongxia Liu4, Yirui Wang12, Zhanlong Shen1, Wenyan Qin2, Peng Guo1, Yuyang Jiang4, Zhibin Hu5,6,7, Hongbing Shen5,6,7, Jing Cheng2,3,12,16, Yinxue Yang14,17, Shan Wang1

1Department of General Surgery, Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing 100044, China

2Health Science Research Institute, Capital Bio Corporation, Beijing 102206, China

3National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China

4The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China

5Section of Clinical Epidemiology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 211166, China

6Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China

7State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China

8Department of Surgery, Ministry of Education Key Lab of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing 100142, China

9Department of Colorectal Surgery, Shanxi Cancer Hospital and Institute, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan 030001, China

10Shanxi Branch Center, National Engineering Research Center for Beijing Biochip Technology, Taiyuan, China

11Department of General Surgery, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, China

12Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China

13Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan 030001, China

14Department of Anal-Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, China

15The Anorectal Department, Gansu Provincial People's Hospital, Lanzhou 730000, China

16The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China

17Ningxia Branch Center, National Engineering Research Center for Beijing Biochip Technology, Yinchuan 750004, China

*These authors have contributed equally to this work

Correspondence to:

Shan Wang, e-mail: shanwang@pkuph.edu.cn

Yinxue Yang, e-mail: fybgsh674@163.com

Jing Cheng, e-mail: jcheng@tsinghua.edu.cn

Keywords: GWAS, colorectal cancer, association

Received: June 09, 2015     Accepted: October 16, 2015     Published: October 26, 2015

ABSTRACT

Genome-wide association studies (GWAS) have reported a number of loci harboring common variants that influence risk of colorectal cancer (CRC) in European descent. But all the SNPs identified explained a small fraction of total heritability. To identify more genetic factors that modify the risk of CRC, especially Chinese Han specific, we conducted a three-stage GWAS including a screening stage (932 CRC cases and 966 controls) and two independent validations (Stage 2: 1,759 CRC cases and 1,875 controls; Stage 3: 943 CRC cases and 1,838 controls). In the combined analyses, we discovered two novel loci associated with CRC: rs12522693 at 5q23.3 (CDC42SE2-CHSY3, OR = 1.31, P = 2.08 × 10−8) and rs17836917 at 17q12 (ASIC2-CCL2, OR = 0.75, P = 4.55 × 10−8). Additionally, we confirmed two previously reported risk loci, rs6983267 at 8q24.21 (OR = 1.17, P = 7.17 × 10−7) and rs10795668 at 10p14 (OR = 0.86, P = 2.96 × 10−6) in our cohorts. These results bring further insights into the CRC susceptibility and advance our understanding on etiology of CRC.


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