Dongying Gu1, Shuwei Li2,3, Mulong Du2,4, Cuiju Tang1, Haiyan Chu2,3, Na Tong2,3, Zhengdong Zhang2,3, Meilin Wang5,6, Jinfei Chen7. 1. Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China. 2. 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. 3. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. 4. Department of Biostatistics, Nanjing Medical University, Nanjing, 211166, People's Republic of China. 5. 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. 6. 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. 7. Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China. jinfeichen@sohu.com.
Abstract
BACKGROUND: Genome-wide association studies have identified genes in the transforming growth factor-β (TGFβ) 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 TGFβ 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.
BACKGROUND: Genome-wide association studies have identified genes in the transforming growth factor-β (TGFβ) 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 TGFβ pathway for further analysis. We used TaqMan technology to genotype these SNPs in a population-based case-control study of 1147 colorectal cancerpatients 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.
Authors: Boris Pasche; Thomas J Knobloch; Yansong Bian; Junjian Liu; Sharbani Phukan; Diana Rosman; Virginia Kaklamani; Lisa Baddi; Farida S Siddiqui; Wendy Frankel; Thomas W Prior; David E Schuller; Amit Agrawal; Jas Lang; M Eileen Dolan; Everett E Vokes; William S Lane; Chiang-Ching Huang; Trinidad Caldes; Antonio Di Cristofano; Heather Hampel; IngMarie Nilsson; Gunnar von Heijne; Riccardo Fodde; V V V S Murty; Albert de la Chapelle; Christopher M Weghorst Journal: JAMA Date: 2005-10-05 Impact factor: 56.272
Authors: Laura Valle; Tarsicio Serena-Acedo; Sandya Liyanarachchi; Heather Hampel; Ilene Comeras; Zhongyuan Li; Qinghua Zeng; Hong-Tao Zhang; Michael J Pennison; Maureen Sadim; Boris Pasche; Stephan M Tanner; Albert de la Chapelle Journal: Science Date: 2008-08-14 Impact factor: 47.728