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

// Kewei Jiang 1, * , Yimin Sun 2, 3, 4, * , Cheng Wang 5, 6, 7, * , Jiafu Ji 8, * , Yaoping Li 9, 10, * , Yingjiang Ye 1, * , Liang Lv 1, 11 , Yong Guo 12 , Sutang Guo 10, 13 , Hai Li 14 , Lianhai Zhang 8 , Yanbing Zhou 11 , Bo Jiang 9 , Yonghong Ren 2 , Youchun Xu 12 , Xiongfei Yang 15 , Hongxia Liu 4 , Yirui Wang 12 , Zhanlong Shen 1 , Wenyan Qin 2 , Peng Guo 1 , Yuyang Jiang 4 , Zhibin Hu 5, 6, 7 , Hongbing Shen 5, 6, 7 , Jing Cheng 2, 3, 12, 16 , Yinxue Yang 14, 17 , Shan Wang 1 1 Department of General Surgery, Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing 100044, China 2 Health Science Research Institute, Capital Bio Corporation, Beijing 102206, China 3 National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China 4 The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China 5 Section of Clinical Epidemiology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 211166, China 6 Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China 7 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China 8 Department of Surgery, Ministry of Education Key Lab of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing 100142, China 9 Department of Colorectal Surgery, Shanxi Cancer Hospital and Institute, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan 030001, China 10 Shanxi Branch Center, National Engineering Research Center for Beijing Biochip Technology, Taiyuan, China 11 Department of General Surgery, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, China 12 Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China 13 Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan 030001, China 14 Department of Anal-Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, China 15 The Anorectal Department, Gansu Provincial People's Hospital, Lanzhou 730000, China 16 The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China 17 Ningxia 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.