title: Identification of a functional polymorphism affecting microRNA binding in the susceptibility locus 1q25.3 for colorectal cancer.
abstract: Genome-wide association studies (GWASs) have identified dozens of susceptibility loci for colorectal cancer (CRC). However, most of them lack functional genetic variants and clear biological mechanisms. MicroRNAs (miRNAs) are small noncoding RNAs involved in a variety of physiological and tumorigenic processes. Here we hypothesized that single nucleotide polymorphisms (SNPs) that affect miRNAs biogenesis and binding, could contribute to CRC risk in the Chinese population. To locate miRNA-related SNPs in established GWAS loci, we initially screened out five candidate SNPs using a systematic bioinformatics analysis. Then, we performed a two-stage case-control study consisting of 2347 cases and 3390 controls, and found a positive polymorphism rs1062044, which presented consistently significant associations with CRC in both stages, and with an odds ratio (OR) = 1.32 (95% confidence interval (95%CI) = 1.18-1.49, P = 3.43E-06) under the dominant model in the combined study. Further luciferase reporter gene assays indicated that the variant G allele obviously improved the specific binding between miR-423-5p and the gene LAMC1. These findings suggested that the functional SNP rs1062044 at 1q25.3 might be a genetic modifier for the occurrence and development of CRC.
authors.affiliation: State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment & Health (Ministry of Education), Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, 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: State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment & Health (Ministry of Education), Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, 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: State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment & Health (Ministry of Education), Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, 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: State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment & Health (Ministry of Education), Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, 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: State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment & Health (Ministry of Education), Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, 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: State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment & Health (Ministry of Education), Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, 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: State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment & Health (Ministry of Education), Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, 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: State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment & Health (Ministry of Education), Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, 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: Key Laboratory for Environment and Health (Ministry of Education), School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment & Health (Ministry of Education), Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jing
authors.identifier: 0000-0002-0040-5839
authors.initials: J
authors.lastname: Gong
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012334:RNA, Neoplasm
keywords: 1q25.3; a functional polymorphism; colorectal cancer; microRNA; susceptibility