TY - JOUR
T1 - Mitochondrial DNA sequence variation and risk of glioma
AU - Samanic, Claudine M.
AU - Teer, Jamie K.
AU - Thompson, Zachary J.
AU - Creed, Jordan H.
AU - Fridley, Brooke L.
AU - Burt Nabors, L.
AU - Williams, Sion L.
AU - Egan, Kathleen M.
N1 - Funding Information:
Funding: This work was supported by grants from the National Institutes of Health (R01CA116174) and the University of Alabama at Birmingham O’Neal Comprehensive Cancer Center Neuro-oncology Research Acceleration Fund, and the H. Lee Moffitt Cancer Center & Research Institute , an NCI-designated Comprehensive Cancer Center ( P30-CA076292 ). The work is based in part on the UK Biobank Resource under application number 16944.
Funding Information:
Funding: This work was supported by grants from the National Institutes of Health (R01CA116174) and the University of Alabama at Birmingham O'Neal Comprehensive Cancer Center Neuro-oncology Research Acceleration Fund, and the H. Lee Moffitt Cancer Center & Research Institute, an NCI-designated Comprehensive Cancer Center (P30-CA076292). The work is based in part on the UK Biobank Resource under application number 16944.
Publisher Copyright:
© 2022 Elsevier B.V. and Mitochondria Research Society
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - Glioblastoma
KW - Glioma
KW - Mitochondrial DNA
KW - UK Biobank
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U2 - 10.1016/j.mito.2022.01.002
DO - 10.1016/j.mito.2022.01.002
M3 - Article
C2 - 35032707
AN - SCOPUS:85122799289
VL - 63
SP - 32
EP - 36
JO - Mitochondrion
JF - Mitochondrion
SN - 1567-7249
ER -
