PMID- 29971498 OWN - NLM STAT- MEDLINE DCOM- 20200316 LR - 20200316 IS - 1435-5922 (Electronic) IS - 0944-1174 (Linking) VI - 54 IP - 2 DP - 2019 Feb TI - A genetic variant located in the miR-532-5p-binding site of TGFBR1 is associated with the colorectal cancer risk. PG - 141-148 LID - 10.1007/s00535-018-1490-y [doi] AB - BACKGROUND: Genome-wide association studies have identified genes in the transforming growth factor-beta (TGFbeta) signaling pathway that are responsible for regulating carcinogenesis. METHODS: We searched for single-nucleotide polymorphisms (SNPs) located within 3'-untranslated regions (3'-UTRs) that might affect the ability of miRNAs to bind genes in the TGFbeta pathway for further analysis. We used TaqMan technology to genotype these SNPs in a population-based case-control study of 1147 colorectal cancer patients and 1203 matched controls in a Chinese population. RESULTS: The rs1590 variant of TGFBR1 exhibited a significant association with colorectal cancer risk. Compared with individuals carrying the rs1590 TT genotype, individuals carrying the GT/GG genotypes had a decreased risk of colorectal cancer [odd ratio (OR) = 0.82, 95% confidence interval (CI) = 0.68-0.97], which was more evident among older individuals with a family history of cancer. Luciferase assays confirmed that the rs1590 T allele altered the capacity of miR-532-5p to bind TGFBR1. CONCLUSIONS: Based on these findings, the rs1590 variant in the 3'-UTR of TGFBR1 may contribute to the susceptibility to colorectal cancer, predominantly by altering miR-532-5p binding. FAU - Gu, Dongying AU - Gu D AD - Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China. FAU - Li, Shuwei AU - Li S AD - Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China. AD - Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Du, Mulong AU - Du M AD - Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China. AD - Department of Biostatistics, Nanjing Medical University, Nanjing, 211166, People's Republic of China. FAU - Tang, Cuiju AU - Tang C AD - Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China. FAU - Chu, Haiyan AU - Chu H AD - Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China. AD - Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Tong, Na AU - Tong N AD - Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China. AD - Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Zhang, Zhengdong AU - Zhang Z AD - Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China. AD - Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. FAU - Wang, Meilin AU - Wang M AD - Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People's Republic of China. mwang@njmu.edu.cn. AD - Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. mwang@njmu.edu.cn. FAU - Chen, Jinfei AU - Chen J AD - Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China. jinfeichen@sohu.com. LA - eng PT - Journal Article DEP - 20180703 PL - Japan TA - J Gastroenterol JT - Journal of gastroenterology JID - 9430794 RN - 0 (3' Untranslated Regions) RN - 0 (MIRN532 microRNA, human) RN - 0 (MicroRNAs) RN - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I) RN - EC 2.7.11.30 (TGFBR1 protein, human) SB - IM MH - 3' Untranslated Regions/genetics MH - Aged MH - Case-Control Studies MH - Colorectal Neoplasms/*genetics MH - Female MH - Genotype MH - Humans MH - Male MH - MicroRNAs/*genetics/metabolism MH - Middle Aged MH - Polymorphism, Single Nucleotide MH - Receptor, Transforming Growth Factor-beta Type I/*genetics MH - Risk Factors OTO - NOTNLM OT - Colorectal cancer OT - Genetic variants OT - Risk OT - TGFbeta EDAT- 2018/07/05 06:00 MHDA- 2020/03/17 06:00 CRDT- 2018/07/05 06:00 PHST- 2018/05/02 00:00 [received] PHST- 2018/06/22 00:00 [accepted] PHST- 2018/07/05 06:00 [pubmed] PHST- 2020/03/17 06:00 [medline] PHST- 2018/07/05 06:00 [entrez] AID - 10.1007/s00535-018-1490-y [pii] AID - 10.1007/s00535-018-1490-y [doi] PST - ppublish SO - J Gastroenterol. 2019 Feb;54(2):141-148. doi: 10.1007/s00535-018-1490-y. Epub 2018 Jul 3.