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An exploratory analysis of common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome

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An Erratum to this article was published on 08 August 2012

Abstract

Purpose

Experimental and epidemiological evidence shows a beneficial role of vitamin D in cancer. In vitro evidence is consistent with a similar protective function in glioma; however, no study has yet examined the potential role of vitamin D in glioma.

Methods

We evaluated the association between common genetic variants in the vitamin D pathway and glioma risk and patient outcome in 622 newly diagnosed glioma cases and 628 healthy controls enrolled in a clinic-based case–control study. Subjects were genotyped for 7 candidate and tagging single nucleotide polymorphisms in the vitamin D receptor and 8 additional variants in NADSYN1, GC, CYP24A1, CYP2R1, and C10ORF88 linked in genome-wide association studies to serum concentrations of vitamin D. Unconditional logistic regression was used to estimate age- and gender-adjusted odds ratios and 95 % confidence intervals for glioma risk according to vitamin D genotypes. Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 320 patients diagnosed with high-grade tumors. P values were uncorrected for multiple comparisons.

Results

Risk of astrocytic tumors was associated with variant alleles in rs3829251 (NADSYN1), rs10741657 (CYP2R1), rs2228570 (Fok1, VDR), and rs731236 (Taq1, VDR). No risk associations were found among oligodendroglial tumors. Survival associations were observed according to variant status for rs1544410 (Bsm1, VDR) and rs6013897 (CYP24A1).

Conclusion

This exploratory analysis provides limited evidence of a role for genetic variation in vitamin D pathway genes with glioma risk and survival.

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Acknowledgments

The authors wish to acknowledge study participants for their contributions. We further wish to thank the clinicians and research staffs at participating medical centers. Special thanks go to Celia Sigua and Marek Wloch of the Tissue Core at Moffitt and Cara Sutcliffe of the Center for Human Genetics Research DNA Resources Core at Vanderbilt University School of Medicine for their work in processing DNA samples, and 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 the genotyping phase of the study. This study was supported by a grant from the National Institutes of Health (CA R01CA116174), a cancer prevention fellowship for Gabriella Anic supported by the National Cancer Institute grant R25T CA147832, as well as institutional funding from the Moffitt Cancer Center, Tampa, FL, and the Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, TN.

Conflict of interest

The authors have no conflicts of interest.

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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, 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 School of Medicine, Atlanta, GA, 30322, USA

    Jeffrey J. Olson

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

    F. Reed Murtagh

  6. Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    Peter A. Forsyth

Authors
  1. Gabriella M. Anic
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  2. Reid C. Thompson
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  3. L. Burton Nabors
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  4. Jeffrey J. Olson
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  5. James E. Browning
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  6. Melissa H. Madden
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  7. F. Reed Murtagh
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  8. Peter A. Forsyth
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  9. Kathleen M. Egan
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Corresponding author

Correspondence to Kathleen M. Egan.

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Anic, G.M., Thompson, R.C., Burton Nabors, L. et al. An exploratory analysis of common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome. Cancer Causes Control 23, 1443–1449 (2012). https://doi.org/10.1007/s10552-012-0018-7

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  • DOI: https://doi.org/10.1007/s10552-012-0018-7

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