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Journal of Gastroenterology

, Volume 54, Issue 2, pp 141–148 | Cite as

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

  • Dongying Gu
  • Shuwei Li
  • Mulong Du
  • Cuiju Tang
  • Haiyan Chu
  • Na Tong
  • Zhengdong Zhang
  • Meilin WangEmail author
  • Jinfei ChenEmail author
Original Article—Alimentary Tract
  • 269 Downloads

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.

Keywords

TGFβ Colorectal cancer Genetic variants Risk 

Abbreviations

GWAS

Genome-wide association study

SNP

Single-nucleotide polymorphism

3′-UTR

3′-untranslated region

HWE

Hardy–Weinberg equilibrium

OR

Odd ratio

CIs

Confidence intervals

TGFβ

Transforming growth factor-β

Notes

Acknowledgements

The authors alone are responsible for the content and writing of the article.

Author contributions

Jinfei Chen and Meilin Wang conceived and designed the experiments. Dongying Gu, Shuwei Li, and Mulong Du wrote the paper. Cuju Tang, Haiyan Chu, and Na Tong contributed reagents/materials/analysis tools. Dongying Gu, Zhengdong Zhang, and Jinfei Chen recruited samples. All authors reviewed the manuscript.

Compliance with ethical standards

Conflict of interest

The authors disclose no potential conflicts of interest.

Supplementary material

535_2018_1490_MOESM1_ESM.docx (562 kb)
Supplementary material 1 (DOCX 562 kb)

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Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Dongying Gu
    • 1
  • Shuwei Li
    • 2
    • 3
  • Mulong Du
    • 2
    • 4
  • Cuiju Tang
    • 1
  • Haiyan Chu
    • 2
    • 3
  • Na Tong
    • 2
    • 3
  • Zhengdong Zhang
    • 2
    • 3
  • Meilin Wang
    • 2
    • 3
    Email author
  • Jinfei Chen
    • 1
    Email author
  1. 1.Department of Oncology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
  2. 2.Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingPeople’s Republic of China
  3. 3.Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public HealthNanjing Medical UniversityNanjingChina
  4. 4.Department of BiostatisticsNanjing Medical UniversityNanjingPeople’s Republic of China

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