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Toenail iron, genetic determinants of iron status, and the risk of glioma

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Abstract

Purpose

Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case–control study.

Methods

Samples were collected a median of 24 days following glioma diagnosis in the cases (10th–90th percentile, range: 10–44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes.

Results

No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ~3 weeks of diagnosis (OR = 0.93; 95 % CI 0.46, 1.87 comparing those with high (≥14 μg/g) vs. low (<6 μg/g) iron levels). In contrast, an inverse association with increasing iron was observed after restricting to cases with a delay of 3 weeks or greater (OR = 0.42; 95 % CI 0.19, 0.95), reflecting potentially insidious effects of advancing disease on iron levels among the cases. No associations were observed for any of the examined genetic variants.

Conclusion

The results do not support a role for body iron stores as a determinant of glioma risk.

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Acknowledgments

The authors wish to acknowledge our study participants and their families. We further wish to thank the clinicians and research staffs at participating medical centers for their contributions. In addition, we acknowledge Dr. Sajeel A. Chowdhary at the Florida Hospital Cancer Institute in Orlando, FL, as well as Harold Colbassani, MD; Dean Gobo, MD; and Christopher Mickler, DO, at Morton Plant Mease Healthcare and Baycare Health System in Clearwater, FL, for their efforts recruiting subjects to the study. The project was supported by the National Institutes of Health (R01CA116174) and institutional funding provided by the Moffitt Cancer Center (Tampa, FL) and the Vanderbilt-Ingram Comprehensive Cancer Center (Nashville, TN). Development of this manuscript was supported in part through a National Cancer Institute postdoctoral fellowship training grant (R25CA147832).

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Authors and Affiliations

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

    Gabriella M. Anic, Melissa H. Madden, James E. Browning & Kathleen M. Egan

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

    Peter A. Forsyth

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

    Reid C. Thompson

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

    L. Burton Nabors

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

    Jeffrey J. Olson

  6. Norton Cancer Institute, Louisville, KY, 40202, USA

    Renato V. LaRocca

  7. University of Missouri Research Reactor, University of Missouri, Columbia, MO, 65211, USA

    John D. Brockman

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  1. Gabriella M. Anic
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Correspondence to Kathleen M. Egan.

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Anic, G.M., Madden, M.H., Thompson, R.C. et al. Toenail iron, genetic determinants of iron status, and the risk of glioma. Cancer Causes Control 24, 2051–2058 (2013). https://doi.org/10.1007/s10552-013-0281-2

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