title: Identification of a functional variant for colorectal cancer risk mapping to chromosome 5q31.1.
abstract: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Juntao
authors.initials: J
authors.lastname: Ke
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Jiao
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Jiaoyuan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|State 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.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
keywords: a functional variant; chromosome 5q31.1; colorectal cancer; rs17716310