Men of African descent have the highest prostate cancer incidence and mortality rates, yet the genetic basis of prostate cancer in African men has been understudied. We used genomic data from 3,963 cases and 3,509 controls from Ghana, Nigeria, Senegal, South Africa and Uganda to infer ancestry-specific genetic architectures and fine-map disease associations. Fifteen independent associations at 8q24.21, 6q22.1 and 11q13.3 reached genome-wide significance, including four new associations. Intriguingly, multiple lead associations are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of prostate cancer differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African prostate cancer associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.
Nature genetics. 2024 Oct 02 [Epub ahead of print]
Rohini Janivara, Wenlong C Chen, Ujani Hazra, Shakuntala Baichoo, Ilir Agalliu, Paidamoyo Kachambwa, Corrine N Simonti, Lyda M Brown, Saanika P Tambe, Michelle S Kim, Maxine Harlemon, Mohamed Jalloh, Dillon Muzondiwa, Daphne Naidoo, Olabode O Ajayi, Nana Yaa Snyper, Lamine Niang, Halimatou Diop, Medina Ndoye, James E Mensah, Afua O D Abrahams, Richard Biritwum, Andrew A Adjei, Akindele O Adebiyi, Olayiwola Shittu, Olufemi Ogunbiyi, Sikiru Adebayo, Maxwell M Nwegbu, Hafees O Ajibola, Olabode P Oluwole, Mustapha A Jamda, Audrey Pentz, Christopher A Haiman, Petrus V Spies, André van der Merwe, Michael B Cook, Stephen J Chanock, Sonja I Berndt, Stephen Watya, Alexander Lubwama, Mazvita Muchengeti, Sean Doherty, Natalie Smyth, David Lounsbury, Brian Fortier, Thomas E Rohan, Judith S Jacobson, Alfred I Neugut, Ann W Hsing, Alexander Gusev, Oseremen I Aisuodionoe-Shadrach, Maureen Joffe, Ben Adusei, Serigne M Gueye, Pedro W Fernandez, Jo McBride, Caroline Andrews, Lindsay N Petersen, Joseph Lachance, Timothy R Rebbeck
School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA., Strengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., University of Mauritius, Réduit, Mauritius., Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA., Centre for Proteomic and Genomic Research, Cape Town, South Africa., Université Cheikh Anta Diop de Dakar, Dakar, Senegal., 37 Military Hospital, Accra, Ghana., Korle-Bu Teaching Hospital and University of Ghana Medical School, Accra, Ghana., Department of Pathology, University of Ghana Medical School, Accra, Ghana., College of Medicine, University of Ibadan, Ibadan, Nigeria., College of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Centre, Abuja, Nigeria., Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA., Uro Care, Kampala, Uganda., National Cancer Registry, National Institute for Communicable Diseases a Division of the National Health Laboratory Service, Johannesburg, South Africa., Division of Urology, Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Dana-Farber Cancer Institute, Boston, MA, USA., Herbert Irving Comprehensive Cancer Center, Columbia University, New York City, NY, USA., Stanford Cancer Institute, Stanford University, Stanford, CA, USA., Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA., School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA. ., Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. .