欧洲遗传血统与儿童室管膜瘤风险相关。
European genetic ancestry associated with risk of childhood ependymoma.
机构信息
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
Department of Medicine, Section of Epidemiology and Population Sciences, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
出版信息
Neuro Oncol. 2020 Nov 26;22(11):1637-1646. doi: 10.1093/neuonc/noaa130.
BACKGROUND
Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations.
METHODS
In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS).
RESULTS
CBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08-1.59, Pmeta = 6.7 × 10-3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45-2.73; P = 2.2 × 10-5) but which was not validated in an independent set of posterior fossa type A patients.
CONCLUSIONS
Interethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.
背景
室管膜瘤是一种组织学定义的中枢神经系统肿瘤，最常见于儿童。观察到种族/民族之间的人群水平发病率差异，欧洲血统的个体风险最高。我们旨在确定欧洲遗传血统的程度是否与美国人群的室管膜瘤风险相关。
方法
在加利福尼亚儿童的多民族研究中（327 例病例，1970 例对照），我们估计了最近混合的西班牙裔和非裔美国人受试者中欧洲、非洲和美洲原住民血统的比例，并使用全基因组数据估计了非西班牙裔白人受试者中的欧洲混合程度。我们测试了全基因组血统差异是否与室管膜瘤风险相关，并进行了混合映射以确定与局部血统的关联。我们还评估了来自美国中央脑肿瘤登记处（CBTRUS）的种族/民族分层室管膜瘤发病率数据。
结果
CBTRUS 数据显示，非洲裔美国人和美洲原住民儿童的室管膜瘤发病率分别比非西班牙裔白人低 33%和 36%。在遗传分析中，报告的西班牙裔和非裔美国人中欧洲血统增加 20%，则室管膜瘤的几率增加 1.31 倍（95%CI：1.08-1.59，Pmeta=6.7×10-3）。此外，东欧亚结构与非西班牙裔白人和西班牙裔的室管膜瘤风险增加相关（P=0.030 和 P=0.043）。混合映射显示 20p13 附近与增加的局部欧洲血统相关的峰，靶向精细映射确定了 RSPO4 附近 rs6039499 处的先导变体（比值比=1.99；95%CI：1.45-2.73；P=2.2×10-5），但在后颅窝 A 型患者的独立样本中未得到验证。
结论
室管膜瘤风险的种间差异在室管膜瘤患者的基因组血统中得到再现，这暗示了未来关联研究的目标区域。
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