Skip to main content

Mitochondrial DNA sequence variation and risk of meningioma

Abstract

Background

Risk factors for meningioma include female gender, African American race, high body mass index (BMI), and exposure to ionizing radiation. Although genome-wide association studies (GWAS) have identified two nuclear genome risk loci for meningioma (rs12770228 and rs2686876), the relation between mitochondrial DNA (mtDNA) sequence variants and meningioma is unknown.

Methods

We examined the association of 42 common germline mtDNA variants (minor allele frequency ≥ 5%), haplogroups, and genes with meningioma in 1080 controls and 478 meningioma cases from a case–control study conducted at medical centers in the southeastern United States. Associations were examined separately for meningioma overall and by WHO grade (n = 409 grade I and n = 69 grade II/III).

Results

Overall, meningioma was significantly associated with being female (OR 2.85; 95% CI 2.21–3.69), self-reported African American race (OR 2.38, 95% CI 1.41–3.99), and being overweight (OR 1.48; 95% CI 1.11–1.97) or obese (OR 1.70; 95% CI 1.25–2.31). The variant m.16362T > C (rs62581341) in the mitochondrial control region was positively associated with grade II/III meningiomas (OR 2.33; 95% CI 1.14–4.77), but not grade I tumors (OR 0.99; 95% CI 0.64–1.53). Haplogroup L, a marker for African ancestry, was associated with meningioma overall (OR 2.92; 95% CI 1.01–8.44). However, after stratifying by self-reported race, this association was only apparent among the few self-reported Caucasians with this haplogroup (OR 6.35; 95% CI 1.56–25.9). No other mtDNA variant, haplogroup, or gene was associated with meningioma.

Conclusion

Common mtDNA variants and major mtDNA haplogroups do not appear to have associations with the odds of developing meningioma.

This is a preview of subscription content, access via your institution.

Data availability

Data will be made available upon request.

Code availability

NA.

References

  1. 1.

    Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS (2020) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013–2017. Neuro Oncol 22(12 Suppl 2):iv1–iv96. https://doi.org/10.1093/neuonc/noaa200

    Article  PubMed  Google Scholar 

  2. 2.

    Kshettry VR, Ostrom QT, Kruchko C, Al-Mefty O, Barnett GH, Barnholtz-Sloan JS (2015) Descriptive epidemiology of World Health Organization grades II and III intracranial meningiomas in the United States. Neuro Oncol 17(8):1166–1173. https://doi.org/10.1093/neuonc/nov069

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Buerki RA, Horbinski CM, Kruser T, Horowitz PM, James CD, Lukas RV (2018) An overview of meningiomas. Future Oncol 14(21):2161–2177. https://doi.org/10.2217/fon-2018-0006

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Walsh KM (2020) Epidemiology of meningiomas. Handb Clin Neurol 169:3–15. https://doi.org/10.1016/B978-0-12-804280-9.00001-9

    Article  PubMed  Google Scholar 

  5. 5.

    Niedermaier T, Behrens G, Schmid D, Schlecht I, Fischer B, Leitzmann MF (2015) Body mass index, physical activity, and risk of adult meningioma and glioma: a meta-analysis. Neurology 85(15):1342–1350. https://doi.org/10.1212/WNL.0000000000002020

    Article  PubMed  Google Scholar 

  6. 6.

    Muskens IS, Wu AH, Porcel J et al (2019) Body mass index, comorbidities, and hormonal factors in relation to meningioma in an ethnically diverse population: the Multiethnic Cohort. Neuro Oncol 21(4):498–507. https://doi.org/10.1093/neuonc/noz005

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Wiedmann M, Brunborg C, Lindemann K et al (2013) Body mass index and the risk of meningioma, glioma and schwannoma in a large prospective cohort study (The HUNT Study). Br J Cancer 109(1):289–294. https://doi.org/10.1038/bjc.2013.304

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Michaud DS, Bove G, Gallo V et al (2011) Anthropometric measures, physical activity, and risk of glioma and meningioma in a large prospective cohort study. Cancer Prev Res (Phila) 4(9):1385–1392. https://doi.org/10.1158/1940-6207.CAPR-11-0014

    Article  Google Scholar 

  9. 9.

    Wiemels J, Wrensch M, Claus EB (2010) Epidemiology and etiology of meningioma. J Neurooncol 99(3):307–314. https://doi.org/10.1007/s11060-010-0386-3

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Brenner AV, Sugiyama H, Preston DL et al (2020) Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958–2009. Eur J Epidemiol 35(6):591–600. https://doi.org/10.1007/s10654-019-00599-y

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Kok JL, Teepen JC, van Leeuwen FE et al (2019) Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort: contributions of radiation dose, exposed cranial volume, and age. Neuro Oncol 21(3):392–403. https://doi.org/10.1093/neuonc/noy124

    Article  PubMed  Google Scholar 

  12. 12.

    Dobbins SE, Broderick P, Melin B et al (2011) Common variation at 10p12.31 near MLLT10 influences meningioma risk. Nat Genet 43(9):825–827. https://doi.org/10.1038/ng.879

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Egan KM, Baskin R, Nabors LB et al (2015) Brain tumor risk according to germ-line variation in the MLLT10 locus. Eur J Hum Genet 23(1):132–134. https://doi.org/10.1038/ejhg.2014.70

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Claus EB, Cornish AJ, Broderick P et al (2018) Genome-wide association analysis identifies a meningioma risk locus at 11p15.5. Neuro Oncol 20(11):1485–1493. https://doi.org/10.1093/neuonc/noy077

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Yeung KY, Dickinson A, Donoghue JF et al (2014) The identification of mitochondrial DNA variants in glioblastoma multiforme. Acta Neuropathol Commun 2:1. https://doi.org/10.1186/2051-5960-2-1

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Dong J, Wong LJ, Mims MP (2018) Mitochondrial inheritance and cancer. Transl Res 202:24–34. https://doi.org/10.1016/j.trsl.2018.06.004

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Strickland M, Stoll EA (2017) Metabolic reprogramming in glioma. Front Cell Dev Biol 5:43. https://doi.org/10.3389/fcell.2017.00043

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Garofano L, Migliozzi S, Oh YT et al (2021) Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities. Nat Cancer 2(2):141–156. https://doi.org/10.1038/s43018-020-00159-4

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Gorelick AN, Kim M, Chatila WK et al (2021) Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA. Nat Metab 3(4):558–570. https://doi.org/10.1038/s42255-021-00378-8

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Yuan Y, Ju YS, Kim Y et al (2020) Comprehensive molecular characterization of mitochondrial genomes in human cancers. Nat Genet 52(3):342–352. https://doi.org/10.1038/s41588-019-0557-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Czarnecka AM, Krawczyk T, Zdrozny M et al (2010) Mitochondrial NADH-dehydrogenase subunit 3 (ND3) polymorphism (A10398G) and sporadic breast cancer in Poland. Breast Cancer Res Treat 121(2):511–518. https://doi.org/10.1007/s10549-009-0358-5

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Ding C, Li R, Wang P, Jin P, Li S, Guo Z (2012) Identification of sequence polymorphisms in the D-loop region of mitochondrial DNA as a risk factor for lung cancer. Mitochondrial DNA 23(4):251–254. https://doi.org/10.3109/19401736.2012.674120

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Jin EH, Sung JK, Lee SI, Hong JH (2018) Mitochondrial NADH dehydrogenase subunit 3 (MTND3) polymorphisms are associated with gastric cancer susceptibility. Int J Med Sci 15(12):1329–1333. https://doi.org/10.7150/ijms.26881

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Errichiello E, Venesio T (2017) Mitochondrial DNA variants in colorectal carcinogenesis: drivers or passengers? J Cancer Res Clin Oncol 143(10):1905–1914. https://doi.org/10.1007/s00432-017-2418-2

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Lam ET, Bracci PM, Holly EA et al (2012) Mitochondrial DNA sequence variation and risk of pancreatic cancer. Cancer Res 72(3):686–695. https://doi.org/10.1158/0008-5472.CAN-11-1682

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Liu S, Shi S, Li Y, Kong D (2016) Identification of sequence nucleotide polymorphisms in the D-loop region of mitochondrial DNA as a risk factor for epithelial ovarian cancer. Mitochondrial DNA A DNA Mapp Seq Anal 27(1):9–11. https://doi.org/10.3109/19401736.2013.867435

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    van Oven M, Kayser M (2009) Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat 30(2):E386–E394. https://doi.org/10.1002/humu.20921

    Article  PubMed  Google Scholar 

  28. 28.

    Kloss-Brandstatter A, Pacher D, Schonherr S et al (2011) HaploGrep: a fast and reliable algorithm for automatic classification of mitochondrial DNA haplogroups. Hum Mutat 32(1):25–32. https://doi.org/10.1002/humu.21382

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Mukherjee S, Biswas D, Epari S et al (2021) Comprehensive proteomic analysis reveals distinct functional modules associated with skull base and supratentorial meningiomas and perturbations in collagen pathway components. J Proteomics 246:104303. https://doi.org/10.1016/j.jprot.2021.104303

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Baldi I, Engelhardt J, Bonnet C et al (2018) Epidemiology of meningiomas. Neurochirurgie 64(1):5–14. https://doi.org/10.1016/j.neuchi.2014.05.006

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Cerhan JH, Butts AM, Syrjanen JA et al (2019) Factors associated with meningioma detected in a population-based sample. Mayo Clin Proc 94(2):254–261. https://doi.org/10.1016/j.mayocp.2018.07.026

    Article  PubMed  Google Scholar 

  32. 32.

    Mohamed Yusoff AA, Mohd Khair SZN, Wan Abdullah WS, Abd Radzak SM, Abdullah JM (2020) Somatic mitochondrial DNA D-loop mutations in meningioma discovered: a preliminary data. J Cancer Res Ther 16(6):1517–1521. https://doi.org/10.4103/jcrt.JCRT_1132_16

    Article  PubMed  Google Scholar 

  33. 33.

    Raule N, Sevini F, Santoro A, Altilia S, Franceschi C (2007) Association studies on human mitochondrial DNA: methodological aspects and results in the most common age-related diseases. Mitochondrion 7(1–2):29–38. https://doi.org/10.1016/j.mito.2006.11.013

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Maca-Meyer N, Gonzalez AM, Larruga JM, Flores C, Cabrera VM (2001) Major genomic mitochondrial lineages delineate early human expansions. BMC Genet 2:13. https://doi.org/10.1186/1471-2156-2-13

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This project is supported by the National Institutes of Health and the University of Alabama at Birmingham O’Neal Comprehensive Cancer Center Neuro-oncology Research Acceleration Fund (Grant no. R01CA116174); Sylvester Comprehensive Cancer Center (Grant no. CA240139); H. Lee Moffitt Cancer Center & Research Institute (Grant no. CA076292).

Author information

Affiliations

Authors

Contributions

All authors contributed to the study conception and design. CMS, JKT, ZJT, JHC, SM, BLF, LBN, SLW, and KME: contributed to conception and design, acquisition of data, interpretation of data. CMS: designed experiments, performed data analysis, and wrote the manuscript. JKT and ZJT: designed experiment and performed data analysis. CMS, JKT, ZJT, JHC, SM, BLF, LBN, SLW, and KME: revised manuscript for critically important intellectual content. All authors approved the final version to be published.

Corresponding author

Correspondence to Kathleen M. Egan.

Ethics declarations

Conflict of interest

The authors declare no potential conflicts of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. The University of South Florida Institutional Review Board approved the study.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 29 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Samanic, C.M., Teer, J.K., Thompson, Z.J. et al. Mitochondrial DNA sequence variation and risk of meningioma. J Neurooncol (2021). https://doi.org/10.1007/s11060-021-03878-5

Download citation

Keywords

  • Meningioma
  • Mitochondria
  • Mitochondrial DNA
  • Haplogroups