Integrated Analysis of Genetic Ancestry and Genomic Alterations across Cancers

Jiao Yuan, Zhongyi Hu, Brandon A. Mahal, Sihai D. Zhao, Kevin H. Kensler, Jingjiang Pi, Xiaowen Hu, Youyou Zhang, Yueying Wang, Junjie Jiang, Chunsheng Li, Xiaomin Zhong, Kathleen T. Montone, Guoqiang Guan, Janos L. Tanyi, Yi Fan, Xiaowei Xu, Mark A. Morgan, Meixiao Long, Yuzhen ZhangRugang Zhang, Anil K. Sood, Timothy R. Rebbeck, Chi V. Dang, Lin Zhang

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

Disparities in cancer care have been a long-standing challenge. We estimated the genetic ancestry of The Cancer Genome Atlas patients, and performed a pan-cancer analysis on the influence of genetic ancestry on genomic alterations. Compared with European Americans, African Americans (AA) with breast, head and neck, and endometrial cancers exhibit a higher level of chromosomal instability, while a lower level of chromosomal instability was observed in AAs with kidney cancers. The frequencies of TP53 mutations and amplification of CCNE1 were increased in AAs in the cancer types showing higher levels of chromosomal instability. We observed lower frequencies of genomic alterations affecting genes in the PI3K pathway in AA patients across cancers. Our result provides insight into genomic contribution to cancer disparities. By analyzing TCGA cohorts, Yuan et al. show that breast, head and neck, and endometrial cancers of African Americans (AA) have higher levels of chromosomal instability than those of European Americans whereas the frequency of genetic alternations in the PI3K pathway in AA patients is lower across cancers.

Original languageEnglish (US)
Pages (from-to)549-560.e9
JournalCancer cell
Volume34
Issue number4
DOIs
StatePublished - Oct 8 2018

Keywords

  • cancer disparities
  • cancer genetics
  • cancer genomics

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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