Journal of gastroenterology · 2018
A genetic variant located in the miR-532-5p-binding site of TGFBR1 is associated with the colorectal cancer risk.
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Gu Dongying, Li Shuwei, Du Mulong, Tang Cuiju, Chu Haiyan, Tong Na, Zhang Zhengdong, Wang Meilin, Chen Jinfei
Аннотация
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.
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.