期刊
MITOCHONDRION
卷 63, 期 -, 页码 32-36出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.mito.2022.01.002
关键词
UK Biobank; Glioma; Glioblastoma; Mitochondrial DNA
资金
- National Institutes of Health [R01CA116174]
- University of Alabama at Birmingham O'Neal Comprehensive Cancer Center Neuro-oncology Research Acceleration Fund
- H. Lee Moffitt Cancer Center & Research Institute
- NCI-designated Comprehensive Cancer Center [P30-CA076292]
This study investigated the association of common germline mtDNA variants and haplogroups with glioma risk. The results found that certain variants were associated with increased or decreased risk of glioma, although these associations were not consistent between the two study populations.
Background: Malignant gliomas are the most common primary adult brain tumors, with a poor prognosis and illdefined 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.
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