title: Common genetic variation in ETV6 is associated with colorectal cancer susceptibility.
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.
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.|Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.|Department of Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.|State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Gu
authors.affiliation: Department of Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Mulong
authors.initials: M
authors.lastname: Du
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Suzhan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Institute for Chemical Carcinogenesis, State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang 110042, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Cell Engineering Research Center, State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.affiliation: Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Institute for Chemical Carcinogenesis, State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Cuiju
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Haina
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang 110042, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jiangbo
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Na
authors.initials: N
authors.lastname: Tong
authors.affiliation: Program for Personalized Cancer Care, NorthShore University Health System, Evanston, Illinois 60201, USA.
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: Program for Personalized Cancer Care, NorthShore University Health System, Evanston, Illinois 60201, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.|Department of Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.|Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein