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Longer genotypically-estimated leukocyte telomere length is associated with increased meningioma risk

  • Clinical Study
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Abstract

Purpose

Telomere length-associated SNPs have been associated with incidence and survival rates for malignant brain tumors such as glioma. Here, we study the influence of genetically determined lymphocyte telomere length (LTL) by comparing telomerase associated SNPs between the most common non-malignant brain tumor, i.e. meningioma, and healthy controls.

Methods/patients

One thousand fifty-three (1053) surgically treated meningioma patients and 4437 controls of Western European ancestry were included. Germline DNA was genotyped for 8 SNPs previously significantly associated with LTL. Genotypically-estimated LTL was then calculated by summing each SNP’s genotypically-specified telomere length increase in base pairs (bp) for each person. Odds ratios for genotypically-estimated LTL in meningioma cases and controls were evaluated using logistic regression with the first two ancestral principal components and sex as covariates.

Results

Three out of the eight evaluated LTL SNPs were significantly associated with increased meningioma risk (rs10936599: OR 1.14, 95% CI 1.01–1.28, rs2736100: OR 1.13, 95% CI 1.03–1.25, rs9420907: OR 1.22, 95% CI 1.07–1.39). Only rs9420907 remained significant after correction for multiple testing. Average genotypically-estimated LTL was significantly longer for those with meningioma compared to controls [mean cases: 560.2 bp (standard error (SE): 4.05 bp), mean controls: 541.5 bp (SE: 2.02 bp), logistic regression p value = 2.13 × 10−5].

Conclusion

Increased genotypically-estimated LTL was significantly associated with increased meningioma risk. A role for telomere length in the pathophysiology of meningioma is novel, and could lead to new insights on the etiology of meningioma.

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Acknowledgements

The authors would like to thank all the participants in this study.

Funding

This work was supported by NIH R01 Grants Nos. CA109468, CA109461, CA109745, CA109473, CA109475; CA52689, NIH R25 Grant No. CA112355, NIH P50 Grant No. CA097257, as well as by the Brain Science Foundation, the Meningioma Mommas, and the University of California, San Francisco Lewis Chair in Brain Tumor Research (MW).

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Authors and Affiliations

  1. Department of Neurosurgery, Brigham and Woman’s Hospital, Boston, MA, USA

    Ivo S. Muskens & Elizabeth B. Claus

  2. Center for Genetic Epidemiology, Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Ivo S. Muskens & Joseph L. Wiemels

  3. Department of Neurological Surgery, School of Medicine, University of California, San Francisco, San Francisco, CA, USA

    Helen M. Hansen, Ivan V. Smirnov, Annette M. Molinaro, Margaret Wrensch & Joseph L. Wiemels

  4. Institute of Human Genetics, University of California, San Francisco, San Francisco, CA, USA

    Margaret Wrensch

  5. Section of Epidemiology and Popular Sciences, Department of Medicine, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Melissa L. Bondy

  6. Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA

    Joellen M. Schildkraut

  7. School of Public Health, Yale University, 60 College St, PO Box 208034, 06520-8034, New Haven, CT, USA

    Elizabeth B. Claus

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Muskens, I.S., Hansen, H.M., Smirnov, I.V. et al. Longer genotypically-estimated leukocyte telomere length is associated with increased meningioma risk. J Neurooncol 142, 479–487 (2019). https://doi.org/10.1007/s11060-019-03119-w

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