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A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population

  • Toxicogenomics
  • Published:
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Abstract

MicroRNAs (miRNAs) are a family of endogenous, small, noncoding RNA molecules that involved in a wide range of biological processes including differentiation, proliferation, and apoptosis. A polymorphism G>C (rs2910164) is located in the stem region opposite to the mature miR-146a sequence. In our study, we investigated whether rs2910164 is associated with the risk of colorectal cancer (CRC) in a Chinese population. We genotyped the rs2910164 polymorphism using TaqMan method and evaluated the association with CRC risk in a case–control study, including 1,147 CRC patients and 1,203 cancer-free controls. Logistic regression models were used to assess the genetic effects on the development of CRC. Overall, we found that rs2910164 was significantly associated with the reduced CRC risk [GC/CC versus GG: adjusted odds ratio (OR) = 0.78, 95 % confidence intervals (CIs) = 0.66–0.93]. In the stratification analysis, this decreased risk was also pronounced among non-smokers (0.75, 0.61–0.93), non-drinkers (0.77, 0.63–0.94), and no family history of cancer (0.79, 0.65–0.95). Furthermore, GC/CC genotypes were associated with reduced CRC susceptibility in intermediate differentiated CRC (0.75, 0.62–0.90), and similar effect was observed in patients with the advanced stage tumor (Dukes C and D) (0.76, 0.61–0.93). In conclusion, our results suggest that miR-146a rs2910164 may contribute to the susceptibility to CRC in a Chinese population. Further larger population-based prospective and functional studies are needed to validate our findings.

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Acknowledgments

This study was partly supported by National Natural Science Foundation of China (81201570, 81102089 and 81230068), National Natural Science Foundation of Jiangsu Province (BK2010080 and BK2011773), the Key Program for Basic Research of Jiangsu Provincial Department of Education (11KJB330002), the Qing Lan Project of Jiangsu Provincial Department of Education, and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China

    Lan Ma & Meilin Wang

  2. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, 818 East Tianyuan Road, Nanjing, 211166, China

    Lan Ma, Haiyan Chu, Na Tong, Zhengdong Zhang & Meilin Wang

  3. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Lingjun Zhu

  4. Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China

    Dongying Gu & Jinfei Chen

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  1. Lan Ma
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  2. Lingjun Zhu
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  3. Dongying Gu
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  4. Haiyan Chu
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  5. Na Tong
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Correspondence to Zhengdong Zhang or Meilin Wang.

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Lan Ma, Lingjun Zhu, and Dongying Gu are contributed equally to this work.

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Ma, L., Zhu, L., Gu, D. et al. A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population. Arch Toxicol 87, 825–833 (2013). https://doi.org/10.1007/s00204-012-1004-2

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