Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers. Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery.
Cancer cell. 2023 Oct 23 [Epub ahead of print]
Evelyn Jiagge, Dexter X Jin, Justin Y Newberg, Tomin Perea-Chamblee, Kelly R Pekala, Christopher Fong, Michele Waters, David Ma, Yvonne Dei-Adomakoh, Gilles Erb, Kanika S Arora, Sophia L Maund, Njoki Njiraini, Atara Ntekim, Susie Kim, Xuechun Bai, Marlene Thomas, Ronwyn van Eeden, Priti Hegde, Justin Jee, Debyani Chakravarty, Nikolaus Schultz, Michael F Berger, Garrett M Frampton, Ethan S Sokol, Jian Carrot-Zhang
Hematology/Oncology Division, Department of Medicine, Henry Ford Health System, Detroit, MI, USA. Electronic address: ., Computational Discovery, Foundation Medicine, Inc., Cambridge, MA, USA. Electronic address: ., Computational Discovery, Foundation Medicine, Inc., Cambridge, MA, USA., Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Haematology, University of Ghana Medical School, Accra, Ghana., Global Product Development Medical Affairs - Oncology, F. Hoffmann-La Roche Ltd, Basel, Switzerland., Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer, New York, NY, USA., Computational Sciences, Genentech, Inc., South San Francisco, CA, USA., Department of Oncology, Kenyatta University Teaching Research and Referral Hospital, Nairobi, Kenya., Department of Radiation Oncology, University of Ibadan, Ibadan, Nigeria., Department of Medical Oncology, Chris Hani Academic Baragwanath Hospital, Johannesburg, South Africa., Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer, New York, NY, USA; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Clinial Genetics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: .