PDTM-33. EUROPEAN GENETIC ANCESTRY ASSOCIATED WITH RISK OF CHILDHOOD EPENDYMOMA. (11th November 2019)

• Record Type: Journal Article
• Authors: Zhang, Chenan; Ostrom, Quinn; Hansen, Helen; de Smith, Adam; Kline, Cassie; Kruchko, Carol; Vaksman, Zalman; Diskin, Sharon; Barnholtz-Sloan, Jill; Ramaswamy, Vijay; Taylor, Michael; Bondy, Melissa; Metayer, Catherine; Wiemels, Joseph; Walsh, Kyle
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 6
• Page Start: vi194
• Page End: vi194
• Publication Date: 2019-11-11
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz175.809
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: BACKGROUND: Ependymoma is a histologically-defined central nervous system tumor most commonly occurring in children. Incidence differs by race/ethnicity, with individuals of European ancestry at highest risk. No large-scale genomic analyses of ependymoma predisposition have been conducted to date. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk. 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 admixed Hispanic and African-American subjects and estimated European substructure 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 European ancestry. We also re-analyzed CBTRUS data to examine subtype-specific differences in ependymoma incidence across racial/ethnic groups. RESULTS: Each 20% increase in European ancestry was associated with 1.31-fold greater odds of ependymoma among Hispanic and African-American subjects (95% CI: 1.08–1.59, Pmeta =6.7×10 –3 ). Among non-Hispanic whites, European ancestral substructure was also significantly associated with ependymoma risk. Local admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and genotype association analysis in the region identified an association upstream of R-spondin 4 that survived Bonferroni correction (P=2.2x10 -5 ) but was not validated in an independent set of posterior fossa type A (PF-EPN-A) patients. In complementary CBTRUS analyses, American Indian/Alaskan Natives were at reduced risk relative to non-Hispanic whites (RR=0.64, 95% CI:0.46–0.87), as were African-Americans (RR=0.67, 95% CI:0.60–0.74) and Asian/Pacific Islanders (RR=0.86, 95% CI:0.73–1.00). Although overall ependymoma rates were similar in U.S. Hispanics (RR=0.96, 95% CI:0.88–1.05), lower rates were observed for myxopapillary ependymoma and other spinal ependymoma. CONCLUSION: Inter-ethnic differences in ependymoma risk vary by histopathologic and potentially molecular subgroup, and are recapitulated in the genomic ancestry of ependymoma patients.