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 Zhang; Rugang Zhang; Anil K Sood; Timothy R Rebbeck; Chi V Dang; Lin Zhang

doi:10.1016/j.ccell.2018.08.019

Integrated Analysis of Genetic Ancestry and Genomic Alterations across Cancers

Cancer Cell. 2018 Oct 8;34(4):549-560.e9. doi: 10.1016/j.ccell.2018.08.019.

Authors

Jiao Yuan¹, Zhongyi Hu¹, Brandon A Mahal², Sihai D Zhao³, Kevin H Kensler⁴, Jingjiang Pi⁵, Xiaowen Hu¹, Youyou Zhang¹, Yueying Wang¹, Junjie Jiang¹, Chunsheng Li¹, Xiaomin Zhong⁶, Kathleen T Montone⁷, Guoqiang Guan⁸, Janos L Tanyi⁹, Yi Fan¹⁰, Xiaowei Xu⁷, Mark A Morgan⁹, Meixiao Long¹¹, Yuzhen Zhang⁵, Rugang Zhang¹², Anil K Sood¹³, Timothy R Rebbeck⁴, Chi V Dang¹⁴, Lin Zhang¹⁵

Affiliations

¹ Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
³ Department of Statistics, University of Illinois at Urbana-Champaign, Champaign, IL 61801, USA.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA 02115, USA.
⁵ Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
⁶ Center for Stem Cell Biology and Tissue Engineering, Department of Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
⁷ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁸ Department of Orthodontics, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹ Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁰ Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹¹ Department of Internal Medicine, Division of Hematology, Ohio State University, Columbus, OH 43210, USA.
¹² Wistar Institute, Philadelphia, PA 19104, USA.
¹³ Center for RNA Interference and Non-coding RNA, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77584, USA.
¹⁴ Wistar Institute, Philadelphia, PA 19104, USA; Ludwig Institute for Cancer Research, New York City, NY 10017, USA.
¹⁵ Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected].

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.

Keywords: cancer disparities; cancer genetics; cancer genomics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Black or African American / genetics
Chromosomal Instability / genetics*
Female
Genomics
Humans
Male
Mutation / genetics*
Neoplasms / genetics*
Phosphatidylinositol 3-Kinases / genetics*
Polymorphism, Single Nucleotide / genetics
White People / genetics

Abstract

Publication types

MeSH terms

Grants and funding