Mitochondrial DNA sequence variation and risk of glioma

Claudine M. Samanic, Jamie K. Teer, Zachary J. Thompson, Jordan H. Creed, Brooke L. Fridley, L. Burt Nabors, Sion L. Williams, Kathleen M. Egan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Malignant gliomas are the most common primary adult brain tumors, with a poor prognosis and ill-defined etiology. Mitochondrial DNA (mtDNA) sequence variation has been linked with certain cancers; however, research on glioma is lacking. Methods: We examined the association of common (minor allele frequency ≥ 5%) germline mtDNA variants and haplogroups with glioma risk in 1,566 glioma cases and 1,017 controls from a US case-control study, and 425 glioma cases and 1,534 matched controls from the UK Biobank cohort (UKB). DNA samples were genotyped using the UK Biobank array that included a set of common and rare mtDNA variants. Risk associations were examined separately for glioblastoma (GBM) and lower grade tumors (non-GBM). Results: In the US study, haplogroup W was inversely associated with glioma when compared with haplogroup H (OR = 0.43, 95%CI: 0.23–0.79); this association was not demonstrated in the UKB (OR = 1.07, 95%CI: 0.47–2.43). In the UKB, the variant m.3010G > A was significantly associated with GBM (OR = 1.32; 95%CI: 1.01–1.73; p = 0.04), but not non-GBM (1.23; 95%CI: 0.78–1.95; p = 0.38); no similar association was observed in the US study. In the US study, the variant m.14798 T > C, was significantly associated with non-GBM (OR = 0.72; 95%CI: 0.53–0.99), but not GBM (OR = 0.86; 95%CI: 0.66–1.11), whereas in the UKB, a positive association was observed between this variant and GBM (OR = 1.46; 95%CI: 1.06–2.02) but not non-GBM (OR = 0.92; 95%CI: 0.52–1.63). None of these associations were significant after adjustment for multiple testing. Conclusion: The association of inherited mtDNA variation, including rare and singleton variants, with glioma risk merits further study.

Original languageEnglish (US)
Pages (from-to)32-36
Number of pages5
StatePublished - Mar 2022
Externally publishedYes


  • Glioblastoma
  • Glioma
  • Mitochondrial DNA
  • UK Biobank

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology


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