Identification of a functional variant for colorectal cancer risk mapping to chromosome 5q31.1
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Juntao Ke1,2,*, Jiao Lou1,2,*, Xueqin Chen1,2, Jiaoyuan Li1,2, Cheng Liu1,2, Yajie Gong1,2, Yang Yang1,2, Ying Zhu1,2, Yi Zhang1,2, Jianbo Tian1,2, Jiang Chang1, Rong Zhong1,2, Jing Gong1,2, Xiaoping Miao1,2
1Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan) and School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
*These authors are contributed equally to this work
Xiaoping Miao, email: email@example.com
Jing Gong, email: firstname.lastname@example.org
Keywords: a functional variant, rs17716310, colorectal cancer, chromosome 5q31.1
Received: January 16, 2016 Accepted: April 11, 2016 Published: May 11, 2016
Genome-wide association studies (GWASs) have established chromosome 5q31.1 as a risk locus for colorectal cancer (CRC). We previously identified a potentially regulatory single nucleotide polymorphism (SNP) rs17716310 within 5q31.1. Now, we extended our study with another independent Chinese population, functional assays and analyses of TCGA (The Cancer Genome Atlas) data. Significant associations between rs17716310 and CRC risk were found in Present Study including 1075 CRC cases and 1999 controls (additive model: OR = 1.149, 95% CI = 1.027–1.286, P = 0.016), and in Combined Study including 1766 cases and 2708 controls (additive model: OR = 1.145, 95% CI = 1.045–1.254, P = 0.004). Dual luciferase reporter gene assays indicated that the variant C allele obviously increased transcriptional activity. Using TCGA datasets, we indicated rs17716310 as a cis expression quantitative trait locus (eQTL) for the gene SMAD5, whose expression was significantly higher in CRC tissues. These findings suggested that the functional polymorphism rs17716310 A > C might be a genetic modifier for CRC, promoting the expression of SMAD5 that belonged to the transforming growth factor beta (TGF-β) signaling pathway.
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