title: A functional polymorphism located at transcription factor binding sites, rs6695837 near LAMC1 gene, confers risk of colorectal cancer in Chinese populations.
abstract: Genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) susceptibility. However, the elucidation of causal SNPs and the biological mechanisms behind are still limited. In this study, we initially performed systematic bioinformatics analyses on CRC GWAS-identified loci to seek for potential functional SNPs located at transcription factor binding sites (TFBSs), and then a two-stage case-control study comprised of 1353 cases and 1448 controls of Chinese populations and functional analyses were conducted. As a result, only one SNP rs6695837 out of the nine candidate SNPs survived after two-stage analyses by Bonferroni correction. In combined analyses, rs6695837 exhibited significant associations with CRC risk (TT: CC, odds ratio (OR) = 1.31, 95% confidence interval (CI) = 1.06-1.63; dominant model, OR = 1.21, 95% CI = 1.03-1.43; additive model, OR = 1.15, 95% CI = 1.03-1.28). Functional annotations by RegulomeDB and rSNPBase indicated its biological role and dual-luciferase reporter assays revealed a significant increase in luciferase expression for the reconstructed plasmid with rs6695837T allele, compared with the one with C allele (PSW480 = 0.0002, PLovo = 0.0003). Further gene expression analyses demonstrated significantly higher expression of LAMC1 gene in CRC tumor tissues than that in adjacent non-cancerous tissues (P = 0.0004). These findings strongly suggest that the functional SNP located at TFBSs, rs6695837 might contribute to CRC susceptibility, and the exact biological mechanism awaits further research.
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Ke
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Jiaoyuan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007797:Laminin / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D007797:Laminin; D014157:Transcription Factors; C089141:laminin gamma 1