| Popis: |
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 1,653 glioma cases and 1,065 controls from a US case-control study, and 432 glioma cases and 1,556 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.14798T > 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. |
