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HFE polymorphisms affect survival of brain tumor patients

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Abstract

The HFE (high iron) protein plays a key role in the regulation of body iron. HFE polymorphisms (H63D and C282Y) are the common genetic variants in Caucasians. Based on frequency data, both HFE polymorphisms have been associated with increased risk in a number of cancers. The prevalence of the two major HFE polymorphisms in a human brain tumor patient populations and the impact of HFE polymorphisms on survival have not been studied. In the present study, there is no overall difference in survival by HFE genotype. However, male GBM patients with H63D HFE (H63D) have poorer overall survival than wild type HFE (WT) male GBM (p = 0.03). In GBM patients with the C282Y HFE polymorphism (C282Y), female patients have poorer survival than male patients (p = 0.05). In addition, female metastatic brain tumor patients with C282Y have shorter survival times post diagnosis than WT patients (p = 0.02) or male metastatic brain tumor patients with C282Y (p = 0.02). There is a tendency toward a lower proportion of H63D genotype in GBM patients than a non-tumor control group (p = 0.09) or other subtypes of brain tumors. In conclusion, our study suggests that HFE genotype impacts survival of brain tumor patients in a gender specific manner. We previously reported that glioma and neuroblastoma cell lines with HFE polymorphisms show greater resistance to chemo and radiotherapy. Taken together, these data suggest HFE genotype is an important consideration for evaluating and planning therapeutic strategies in brain tumor patients.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

CBTRUS:

Central Brain Tumor Registry of the United States

C282Y:

C282Y HFE polymorphism

GBM:

Glioblastoma

HCC:

Hepatocellular carcinoma

H63D:

H63D HFE polymorphism

Tf:

Transferrin

TfR:

Transferrin receptor

WT:

Wild type

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Acknowledgments

We thank the macromolecular synthesis core and functional genomics core at the Penn State Hershey Medical Center/Penn State Hershey College of Medicine for primer synthesis and DNA sequencing. We also thank to the research coordinators, data coordinators, and brain tumor patients who participate in our study. This work was supported in part by the Tara Leah Witmer Endowment and Pennsylvania Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparing of the manuscript.

Conflict of interest

Connor is partial owner of NuHope LLC which has a financial interest in development of compounds for treating brain tumors that were initially screened using cell lines chosen for HFE genotype. Lee has a royalty agreement with NuHope LLC.

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Authors and Affiliations

  1. Department of Neurosurgery, H110, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Penn State Hershey Cancer Institute, 500 University Drive (H110), Hershey, PA, 17033-0850, USA

    Sang Y. Lee, Becky Slagle-Webb, Jonas M. Sheehan, Michael Glantz & James R. Connor

  2. Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Penn State Hershey Cancer Institute, Hershey, PA, 17033, USA

    Junjia Zhu & Joshua E. Muscat

Authors
  1. Sang Y. Lee
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  2. Becky Slagle-Webb
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  3. Jonas M. Sheehan
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  4. Junjia Zhu
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  7. James R. Connor
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Correspondence to Sang Y. Lee.

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Lee, S.Y., Slagle-Webb, B., Sheehan, J.M. et al. HFE polymorphisms affect survival of brain tumor patients. J Neurooncol 122, 97–104 (2015). https://doi.org/10.1007/s11060-014-1681-1

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  • DOI: https://doi.org/10.1007/s11060-014-1681-1

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