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

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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.

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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

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Acknowledgements

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

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Author notes

  1. Dongying Gu and Shuwei Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China

    Dongying Gu, Cuiju Tang & Jinfei Chen

  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

    Shuwei Li, Mulong Du, Haiyan Chu, Na Tong, Zhengdong Zhang & Meilin Wang

  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

    Shuwei Li, Haiyan Chu, Na Tong, Zhengdong Zhang & Meilin Wang

  4. Department of Biostatistics, Nanjing Medical University, Nanjing, 211166, People’s Republic of China

    Mulong Du

Authors
  1. Dongying Gu
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  2. Shuwei Li
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  3. Mulong Du
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  4. Cuiju Tang
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  7. Zhengdong Zhang
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  8. Meilin Wang
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  9. Jinfei Chen
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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.

Corresponding authors

Correspondence to Meilin Wang or Jinfei Chen.

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Conflict of interest

The authors disclose no potential conflicts of interest.

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Gu, D., Li, S., Du, M. et al. A genetic variant located in the miR-532-5p-binding site of TGFBR1 is associated with the colorectal cancer risk. J Gastroenterol 54, 141–148 (2019). https://doi.org/10.1007/s00535-018-1490-y

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  • DOI: https://doi.org/10.1007/s00535-018-1490-y

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