Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
J Neurooncol. 2021 Dec;155(3):319-324. doi: 10.1007/s11060-021-03878-5. Epub 2021 Oct 20.
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.
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).
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.
Common mtDNA variants and major mtDNA haplogroups do not appear to have associations with the odds of developing meningioma.
脑膜瘤的风险因素包括女性性别、非裔美国人种族、高身体质量指数（BMI）和电离辐射暴露。尽管全基因组关联研究（GWAS）已经确定了脑膜瘤的两个核基因组风险位点（rs12770228 和 rs2686876），但线粒体 DNA（mtDNA）序列变异与脑膜瘤之间的关系尚不清楚。
我们在美国东南部医疗中心进行的病例对照研究中，检查了 1080 名对照和 478 名脑膜瘤病例中 42 个常见的种系 mtDNA 变体（次要等位基因频率≥5%）、单倍群和基因与脑膜瘤的关联。分别检查了所有脑膜瘤以及世卫组织分级（n=409 级 I 和 n=69 级 II/III）的关联。
总体而言，脑膜瘤与女性（OR 2.85；95%CI 2.21-3.69）、自我报告的非裔美国人种族（OR 2.38，95%CI 1.41-3.99）和超重（OR 1.48；95%CI 1.11-1.97）或肥胖（OR 1.70；95%CI 1.25-2.31）显著相关。线粒体控制区的变体 m.16362T> C（rs62581341）与 II/III 级脑膜瘤呈正相关（OR 2.33；95%CI 1.14-4.77），但与 I 级肿瘤无关（OR 0.99；95%CI 0.64-1.53）。标志着非洲血统的单倍群 L 与脑膜瘤总体相关（OR 2.92；95%CI 1.01-8.44）。然而，在按自我报告的种族进行分层后，这种关联仅在少数自我报告为具有该单倍群的白种人中明显（OR 6.35；95%CI 1.56-25.9）。没有其他 mtDNA 变体、单倍群或基因与脑膜瘤相关。
常见的 mtDNA 变体和主要的 mtDNA 单倍群似乎与脑膜瘤的发病几率没有关联。
