A genetic variant located in the miR-532-5p-binding site of TGFBR1 is associated with the colorectal cancer risk

作者：Gu, Dongying; Li, Shuwei; Du, Mulong; Tang, Cuiju; Chu, Haiyan; Tong, Na; Zhang, Zhengdong; Wang, Meilin^*; Chen, Jinfei^*

来源：Journal of Gastroenterology, 2019, 54(2): 141-148.

DOI：10.1007/s00535-018-1490-y

• TGF
• Colorectal cancer
• Genetic variants
• Risk

BackgroundGenome-wide association studies have identified genes in the transforming growth factor- (TGF) signaling pathway that are responsible for regulating carcinogenesis.MethodsWe 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 TGF 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.ResultsThe 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.ConclusionsBased 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.

• 出版日期2019-2
• 单位南京医科大学