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A Genetic Variant in miR-196a2 Increased Digestive System Cancer Risks: A Meta-Analysis of 15 Case-Control Studies

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  • Jing Guo
  • Mingjuan Jin
  • Mingwu Zhang
  • Kun Chen

Abstract

Background: MicroRNAs (miRNAs) negatively regulate the gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between single nucleotide polymorphism (SNP) in miR-196a2 rs11614913 and the susceptibility of digestive system cancers was inconsistent in previous studies. Methodology/Principal Findings: An updated meta-analysis based on 15 independent case-control studies consisting of 4999 cancer patients and 7606 controls was performed to address this association. It was found that miR-196a2 polymorphism significantly elevated the risks of digestive system cancers (CT vs. TT, OR = 1.25, 95% CI = 1.07–1.45; CC vs. TT, OR = 1.38, 95% CI = 1.13–1.67; CC/CT vs. TT, OR = 1.29, 95% CI = 1.10–1.50; CC vs. CT/TT, OR = 1.14, 95% CI = 1.01–1.30; C vs. T, OR = 1.15, 95% CI = 1.05–1.26). We also found that variant in miR-196a2 increased the susceptibility of colorectal cancer (CRC) (CT vs. TT, OR = 1.23, 95% CI = 1.04–1.44; CC vs. TT, OR = 1.32, 95% CI = 1.08–1.61; CC/CT vs. TT, OR = 1.25, 95% CI = 1.07–1.46; C vs. T, OR = 1.15, 95% CI = 1.05–1.28), while the association in recessive model (CC vs. CT/TT, OR = 1.16, 95% CI = 0.98–1.38) showed a marginal significance. Additionally, significant association between miR-196a2 polymorphism and increased risk of hepatocellular cancer (HCC) was detected. By stratifying tumors on the basis of site of origin, source of controls, ethnicity and allele frequency in controls, elevated cancer risks were observed. Conclusion/Significance: Our findings suggest the significant association between miR-196a2 polymorphism and increased susceptibility of digestive system cancers, especially of CRC, HCC and Asians. Besides, C allele may contribute to increased digestive cancer risks.

Suggested Citation

  • Jing Guo & Mingjuan Jin & Mingwu Zhang & Kun Chen, 2012. "A Genetic Variant in miR-196a2 Increased Digestive System Cancer Risks: A Meta-Analysis of 15 Case-Control Studies," PLOS ONE, Public Library of Science, vol. 7(1), pages 1-7, January.
  • Handle: RePEc:plo:pone00:0030585
    DOI: 10.1371/journal.pone.0030585
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    References listed on IDEAS

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    1. Wei Xu & Jijun Xu & Shifeng Liu & Bo Chen & Xueli Wang & Yan Li & Yun Qian & Weihong Zhao & Jianqing Wu, 2011. "Effects of Common Polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on Cancer Susceptibility: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-7, May.
    2. Haiyan Chu & Meilin Wang & Danni Shi & Lan Ma & Zhizhong Zhang & Na Tong & Xinying Huo & Wei Wang & Dewei Luo & Yan Gao & Zhengdong Zhang, 2011. "Hsa-miR-196a2 Rs11614913 Polymorphism Contributes to Cancer Susceptibility: Evidence from 15 Case-Control Studies," PLOS ONE, Public Library of Science, vol. 6(3), pages 1-6, March.
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    4. Kshitij Srivastava & Anvesha Srivastava, 2012. "Comprehensive Review of Genetic Association Studies and Meta-Analyses on miRNA Polymorphisms and Cancer Risk," PLOS ONE, Public Library of Science, vol. 7(11), pages 1-1, November.
    5. Li Li & Yunjian Sheng & Lin Lv & Jian Gao, 2013. "The Association between Two MicroRNA Variants (miR-499, miR-149) and Gastrointestinal Cancer Risk: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-1, November.
    6. Changzheng Li & Weijun Fu & Yu Zhang & Liang Zhou & Zhi Mao & Weiran Lv & Juan Li & Ye Zhou, 2015. "Meta-Analysis of MicroRNA-146a rs2910164 G>C Polymorphism Association with Autoimmune Diseases Susceptibility, an Update Based on 24 Studies," PLOS ONE, Public Library of Science, vol. 10(4), pages 1-12, April.
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    8. Hui-Rong Xu & Zhong-Fa Xu & Yan-Lai Sun & Jian-Jun Han & Zeng-Jun Li, 2013. "The −842G/C Polymorphisms of PIN1 Contributes to Cancer Risk: A Meta-Analysis of 10 Case-Control Studies," PLOS ONE, Public Library of Science, vol. 8(8), pages 1-7, August.
    9. Zhengrong Yuan & Xu Zeng & Dan Yang & Weilu Wang & Zhihua Liu, 2013. "Effects of Common Polymorphism rs11614913 in Hsa-miR-196a2 on Lung Cancer Risk," PLOS ONE, Public Library of Science, vol. 8(4), pages 1-8, April.
    10. Zhongxia Wang & Yin Cao & Chunping Jiang & Guang Yang & Junhua Wu & Yitao Ding, 2012. "Lack of Association of Two Common Polymorphisms rs2910164 and rs11614913 with Susceptibility to Hepatocellular Carcinoma: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-8, June.

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