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Erschienen in:

22.02.2019 | Clinical Study

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

verfasst von: Ivo S. Muskens, Helen M. Hansen, Ivan V. Smirnov, Annette M. Molinaro, Melissa L. Bondy, Joellen M. Schildkraut, Margaret Wrensch, Joseph L. Wiemels, Elizabeth B. Claus

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2019

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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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Titel: Longer genotypically-estimated leukocyte telomere length is associated with increased meningioma risk
verfasst von: Ivo S. Muskens
Helen M. Hansen
Ivan V. Smirnov
Annette M. Molinaro
Melissa L. Bondy
Joellen M. Schildkraut
Margaret Wrensch
Joseph L. Wiemels
Elizabeth B. Claus
Publikationsdatum: 22.02.2019
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2019
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-019-03119-w

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