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A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma

Journal of Neuro-Oncology volume 105, pages 639–646 (2011)Cite this article

Abstract

MicroRNAs (miRNAs) are non-coding RNAs that function as post-transcriptional regulators of tumor suppressors and oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs may contribute to carcinogenesis by altering expression of miRNAs and their targets. A G>C polymorphism (rs2910164) in the miR-146a precursor sequence leads to a functional change associated with the risk for numerous malignancies. A role for this SNP in glioma pathogenesis has not yet been examined. We investigated whether rs2910164 genotypes influence glioma risk and prognosis in a multi-center case–control study comprised of 593 Caucasian glioma cases and 614 community-based controls. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for rs2910164 genotypes according to case status. Cox proportional hazards regression modeling was used to estimate hazards ratios (HR) and 95% CIs according to genotype among glioblastomas, the most lethal glioma subtype. An increased glioma risk was observed among rs2910164 minor allele (C) carriers (per allele OR (95% CI) = 1.22 (1.01–1.46, p trend = 0.039)). The association was stronger among older subjects carrying at least one copy of the C allele (OR (95% CI) = 1.38 (1.04–1.83, P = 0.026). Mortality was increased among minor allele carriers (HR (95% CI) = 1.33 (1.03–1.72, P = 0.029)), with the association largely restricted to females (HR (95% CI) = 2.02 (1.28–3.17, P = 0.002)). We provide novel data suggesting rs2910164 genotype may contribute to glioma susceptibility and outcome. Future studies are warranted to replicate these findings and characterize mechanisms underlying these associations.

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Acknowledgments

The authors wish to acknowledge the study participants without whom the research would not have been possible. We further wish to thank the clinicians and research staffs at participating medical centers for their contributions. Finally, we thank Ms. Anna Konidari and staff at the Center for Genome Technology at the Hussman Institute for Human Genomics, University of Miami for their expert technical assistance in genotyping. The project was supported by the National Institutes of Health (CA R01CA116174) and institutional funding provided by the Moffitt Cancer Center (Tampa, FL) and the Vanderbilt-Ingram Comprehensive Cancer Center (Nashville, TN).

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Affiliations

  1. Department of Cancer Epidemiology, Division of Population Sciences, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, MRC-CANCONT, Tampa, FL, 33612-9416, USA

    Jennifer Permuth-Wey, James E. Browning, Melissa H. Madden & Kathleen M. Egan

  2. Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Reid C. Thompson

  3. Neuro-oncology Program, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    L. Burton Nabors

  4. Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Jeffrey J. Olson

  5. Department of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA

    Y. Ann Chen

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  1. Jennifer Permuth-Wey
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  2. Reid C. Thompson
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  6. Melissa H. Madden
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  7. Y. Ann Chen
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  8. Kathleen M. Egan
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Correspondence to Kathleen M. Egan.

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Permuth-Wey, J., Thompson, R.C., Burton Nabors, L. et al. A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma. J Neurooncol 105, 639–646 (2011). https://doi.org/10.1007/s11060-011-0634-1

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  • DOI: https://doi.org/10.1007/s11060-011-0634-1

Keywords

  • Genotype
  • Glioma
  • Susceptibility
  • Single nucleotide polymorphism
  • MicroRNA