Common genetic variation in ETV6 is associated with colorectal cancer susceptibility

Meilin Wang (), Dongying Gu, Mulong Du, Zhi Xu, Suzhan Zhang, Lingjun Zhu, Jiachun Lu, Rui Zhang, Jinliang Xing, Xiaoping Miao, Haiyan Chu, Zhibin Hu, Lei Yang, Cuiju Tang, Lei Pan, Haina Du, Jian Zhao, Jiangbo Du, Na Tong, Jielin Sun, Hongbing Shen, Jianfeng Xu, Zhengdong Zhang () and Jinfei Chen ()
Additional contact information
Meilin Wang: Nanjing First Hospital, Nanjing Medical University
Dongying Gu: Nanjing First Hospital, Nanjing Medical University
Mulong Du: Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University
Zhi Xu: Nanjing First Hospital, Nanjing Medical University
Suzhan Zhang: Second Affiliated Hospital, Zhejiang University School of Medicine
Lingjun Zhu: First Affiliated Hospital of Nanjing Medical University
Jiachun Lu: Institute for Chemical Carcinogenesis, State Key Lab of Respiratory Disease, Guangzhou Medical University
Rui Zhang: Liaoning Cancer Hospital and Institute
Jinliang Xing: State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University
Xiaoping Miao: School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
Haiyan Chu: Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University
Zhibin Hu: Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University
Lei Yang: Institute for Chemical Carcinogenesis, State Key Lab of Respiratory Disease, Guangzhou Medical University
Cuiju Tang: Nanjing First Hospital, Nanjing Medical University
Lei Pan: Second Affiliated Hospital, Zhejiang University School of Medicine
Haina Du: First Affiliated Hospital of Nanjing Medical University
Jian Zhao: Liaoning Cancer Hospital and Institute
Jiangbo Du: School of Public Health, Nanjing Medical University
Na Tong: Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University
Jielin Sun: Program for Personalized Cancer Care, NorthShore University Health System
Hongbing Shen: Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University
Jianfeng Xu: Program for Personalized Cancer Care, NorthShore University Health System
Zhengdong Zhang: Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University
Jinfei Chen: Nanjing First Hospital, Nanjing Medical University

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract Genome-wide association studies (GWASs) have identified multiple susceptibility loci for colorectal cancer, but much of heritability remains unexplained. To identify additional susceptibility loci for colorectal cancer, here we perform a GWAS in 1,023 cases and 1,306 controls and replicate the findings in seven independent samples from China, comprising 5,317 cases and 6,887 controls. We find a variant at 12p13.2 associated with colorectal cancer risk (rs2238126 in ETV6, P=2.67 × 10−10). We replicate this association in an additional 1,046 cases and 1,076 controls of European ancestry (P=0.034). The G allele of rs2238126 confers earlier age at onset of colorectal cancer (P=1.98 × 10−6) and reduces the binding affinity of transcriptional enhancer MAX. The mRNA level of ETV6 is significantly lower in colorectal tumours than in paired normal tissues. Our findings highlight the potential importance of genetic variation in ETV6 conferring susceptibility to colorectal cancer.

Date: 2016
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DOI: 10.1038/ncomms11478

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