Trans-ethnic variation in germline variants of patients with renal cell carcinoma
Sarah Abou Alaiwi,
Amin H. Nassar,
Elio Adib,
Stefan M. Groha,
Elie W. Akl,
Bradley A. McGregor,
Edward D. Esplin,
Shan Yang,
Kathryn Hatchell,
Vincent Fusaro,
Sarah Nielsen,
David J. Kwiatkowski,
Guru P. Sonpavde,
Mark Pomerantz,
Judy E. Garber,
Matthew L. Freedman,
Huma Q. Rana,
Alexander Gusev,
Toni K. Choueiri
Affiliations
Sarah Abou Alaiwi
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Amin H. Nassar
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine and Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Elio Adib
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine and Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Stefan M. Groha
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Elie W. Akl
Division of Pulmonary and Critical Care Medicine and Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Bradley A. McGregor
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Edward D. Esplin
Invitae Corporation, San Francisco, CA, USA
Shan Yang
Invitae Corporation, San Francisco, CA, USA
Kathryn Hatchell
Invitae Corporation, San Francisco, CA, USA
Vincent Fusaro
Invitae Corporation, San Francisco, CA, USA
Sarah Nielsen
Invitae Corporation, San Francisco, CA, USA
David J. Kwiatkowski
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine and Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Guru P. Sonpavde
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Mark Pomerantz
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Judy E. Garber
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Division of Population Sciences, Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA
Matthew L. Freedman
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Huma Q. Rana
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Division of Population Sciences, Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA
Alexander Gusev
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Toni K. Choueiri
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine and Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; Corresponding author
Summary: Prior studies of the renal cell carcinoma (RCC) germline landscape investigated predominantly patients of European ancestry. We examine the frequency of germline pathogenic and likely pathogenic (P/LP) variants in 1,829 patients with RCC from various ancestries. Overall, P/LP variants are found in 17% of patients, among whom 10.3% harbor one or more clinically actionable variants with potential preventive or therapeutic utility. Patients of African ancestry with RCC harbor significantly more P/LP variants in FH compared to patients of non-African ancestry with RCC and African controls from the Genome Aggregation Database (gnomAD). Patients of non-African ancestry have significantly more P/LP variants in CHEK2 compared to patients of African ancestry with RCC and non-Finnish Europeans controls. Non-Africans with RCC have more actionable variants compared to Africans with RCC. This work helps understand the underlying biological differences in RCC between Africans and non-Africans and paves the way to more comprehensive genomic characterization of underrepresented populations.
