Common genetic variation in ETV6 is associated with colorectal cancer susceptibility

• Published in: Nature communications Vol. 7; no. 1; pp. 11478 - 9
• Main Authors: Wang, Meilin, Gu, Dongying, Du, Mulong, Xu, Zhi, Zhang, Suzhan, Zhu, Lingjun, Lu, Jiachun, Zhang, Rui, Xing, Jinliang, Miao, Xiaoping, Chu, Haiyan, Hu, Zhibin, Yang, Lei, Tang, Cuiju, Pan, Lei, Du, Haina, Zhao, Jian, Du, Jiangbo, Tong, Na, Sun, Jielin, Shen, Hongbing, Xu, Jianfeng, Zhang, Zhengdong, Chen, Jinfei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.05.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/205/2138; 631/208/457/649; 631/67/68; 692/699/67/1504/1885; Alleles; Asian People - genetics; Cell Line, Tumor; Colorectal cancer; Colorectal Neoplasms - ethnology; Colorectal Neoplasms - genetics; Epidemiology; ETS Translocation Variant 6 Protein; Female; Gene Frequency; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study - methods; Genomes; Genotype; HCT116 Cells; Health risk assessment; Hospitals; Humanities and Social Sciences; Humans; Laboratories; Male; Middle Aged; multidisciplinary; Oncology; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-ets - genetics; Public health; Repressor Proteins - genetics; Risk Factors; Science; Science (multidisciplinary); Toxicology; White People - genetics; Yeast; China
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11478

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. Genome-wide association studies have been performed to identify genetic variants that are associated with susceptibility to colorectal cancer. Here, the authors expand on these studies and identify a variant that regulates the expression of ETV6 and find that over-expression of ETV6 blocks cell proliferation in vitro .