Ivo S Muskens1,2, Helen M Hansen3, Ivan V Smirnov3, Annette M Molinaro3, Melissa L Bondy4, Joellen M Schildkraut5, Margaret Wrensch3,6, Joseph L Wiemels2,3, Elizabeth B Claus7,8. 1. Department of Neurosurgery, Brigham and Woman's Hospital, Boston, MA, USA. 2. Center for Genetic Epidemiology, Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 3. Department of Neurological Surgery, School of Medicine, University of California, San Francisco, San Francisco, CA, USA. 4. Section of Epidemiology and Popular Sciences, Department of Medicine, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA. 5. Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA. 6. Institute of Human Genetics, University of California, San Francisco, San Francisco, CA, USA. 7. Department of Neurosurgery, Brigham and Woman's Hospital, Boston, MA, USA. elizabeth.claus@yale.edu. 8. School of Public Health, Yale University, 60 College St, PO Box 208034, 06520-8034, New Haven, CT, USA. elizabeth.claus@yale.edu.
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.
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 meningiomapatients 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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