Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa

Rohini Janivara¹, Wenlong C Chen^{2

3

4}, Ujani Hazra¹, Shakuntala Baichoo⁵, Ilir Agalliu⁶, Paidamoyo Kachambwa^{7

8}, Corrine N Simonti¹, Lyda M Brown¹, Saanika P Tambe¹, Michelle S Kim¹, Maxine Harlemon¹, Mohamed Jalloh^{9

10}, Dillon Muzondiwa⁷, Daphne Naidoo⁷, Olabode O Ajayi⁷, Nana Yaa Snyper¹¹, Lamine Niang⁹, Halimatou Diop⁹, Medina Ndoye⁹, James E Mensah¹², Afua O D Abrahams¹², Richard Biritwum¹², Andrew A Adjei¹³, Akindele O Adebiyi¹⁴, Olayiwola Shittu¹⁴, Olufemi Ogunbiyi¹⁴, Sikiru Adebayo¹⁴, Maxwell M Nwegbu¹⁵, Hafees O Ajibola¹⁵, Olabode P Oluwole¹⁵, Mustapha A Jamda¹⁵, Audrey Pentz², Christopher A Haiman¹⁶, Petrus V Spies¹⁷, André van der Merwe¹⁷, Michael B Cook¹⁸, Stephen J Chanock¹⁸, Sonja I Berndt¹⁸, Stephen Watya¹⁹, Alexander Lubwama¹⁹, Mazvita Muchengeti⁴, Sean Doherty²⁰, Natalie Smyth³, David Lounsbury⁶, Brian Fortier²¹, Thomas E Rohan⁶, Judith S Jacobson²², Alfred I Neugut²², Ann W Hsing²³, Alexander Gusev²⁴, Oseremen I Aisuodionoe-Shadrach¹⁵, Maureen Joffe², Ben Adusei¹¹, Serigne M Gueye⁹, Pedro W Fernandez¹⁷, Jo McBride⁷, Caroline Andrews²¹, Lindsay N Petersen^{7

8}, Joseph Lachance^#²⁵, Timothy R Rebbeck^#^{26

27}

Affiliations

¹ School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
² Strengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
³ Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ National Cancer Registry, National Institute for Communicable Diseases a Division of the National Health Laboratory Service, Johannesburg, South Africa.
⁵ University of Mauritius, Réduit, Mauritius.
⁶ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
⁷ Centre for Proteomic and Genomic Research, Cape Town, South Africa.
⁸ Mediclinic Precise Southern Africa, Cape Town, South Africa.
⁹ Université Cheikh Anta Diop de Dakar, Dakar, Senegal.
¹⁰ Université Iba Der Thiam de Thiès, Thiès, Senegal.
¹¹ 37 Military Hospital, Accra, Ghana.
¹² Korle-Bu Teaching Hospital and University of Ghana Medical School, Accra, Ghana.
¹³ Department of Pathology, University of Ghana Medical School, Accra, Ghana.
¹⁴ College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁵ College of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Centre, Abuja, Nigeria.
¹⁶ Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁷ Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
¹⁸ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
¹⁹ Uro Care, Kampala, Uganda.
²⁰ Division of Urology, Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²¹ Dana-Farber Cancer Institute, Boston, MA, USA.
²² Herbert Irving Comprehensive Cancer Center, Columbia University, New York City, NY, USA.
²³ Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
²⁴ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
²⁵ School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA. joseph.lachance@biology.gatech.edu.
²⁶ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. timothy_rebbeck@dfci.harvard.edu.
²⁷ Harvard T.H. Chan School of Public Health, Boston, MA, USA. timothy_rebbeck@dfci.harvard.edu.

^# Contributed equally.

PMID: 39358599
DOI: 10.1038/s41588-024-01931-3

Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa

Rohini Janivara et al. Nat Genet. 2024 Oct.

. 2024 Oct;56(10):2093-2103.

doi: 10.1038/s41588-024-01931-3. Epub 2024 Oct 2.

Authors

Affiliations

¹ School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
² Strengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
³ Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ National Cancer Registry, National Institute for Communicable Diseases a Division of the National Health Laboratory Service, Johannesburg, South Africa.
⁵ University of Mauritius, Réduit, Mauritius.
⁶ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
⁷ Centre for Proteomic and Genomic Research, Cape Town, South Africa.
⁸ Mediclinic Precise Southern Africa, Cape Town, South Africa.
⁹ Université Cheikh Anta Diop de Dakar, Dakar, Senegal.
¹⁰ Université Iba Der Thiam de Thiès, Thiès, Senegal.
¹¹ 37 Military Hospital, Accra, Ghana.
¹² Korle-Bu Teaching Hospital and University of Ghana Medical School, Accra, Ghana.
¹³ Department of Pathology, University of Ghana Medical School, Accra, Ghana.
¹⁴ College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁵ College of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Centre, Abuja, Nigeria.
¹⁶ Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁷ Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
¹⁸ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
¹⁹ Uro Care, Kampala, Uganda.
²⁰ Division of Urology, Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²¹ Dana-Farber Cancer Institute, Boston, MA, USA.
²² Herbert Irving Comprehensive Cancer Center, Columbia University, New York City, NY, USA.
²³ Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
²⁴ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
²⁵ School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA. joseph.lachance@biology.gatech.edu.
²⁶ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. timothy_rebbeck@dfci.harvard.edu.
²⁷ Harvard T.H. Chan School of Public Health, Boston, MA, USA. timothy_rebbeck@dfci.harvard.edu.

^# Contributed equally.

PMID: 39358599
DOI: 10.1038/s41588-024-01931-3

Abstract

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.

PubMed Disclaimer

Update of

Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.
Rebbeck T, Janivara R, Chen W, Hazra U, Baichoo S, Agalliu I, Kachambwa P, Simonti C, Brown L, Tambe S, Kim M, Harlemon M, Jalloh M, Muzondiwa D, Naidoo D, Ajayi O, Snyper N, Niang L, Diop H, Ndoye M, Mensah J, Darkwa-Abrahams A, Biritwum R, Adjei A, Adebiyi A, Shittu O, Ogunbiyi O, Adebayo S, Nwegbu M, Ajibola H, Oluwole O, Jamda M, Pentz A, Haiman C, Spies P, Van der Merwe A, Cook M, Chanock SJ, Berndt SI, Watya S, Lubwama A, Muchengeti M, Doherty S, Smyth N, Lounsbury D, Fortier B, Rohan T, Jacobson J, Neugut A, Hsing A, Gusev A, Aisuodionoe-Shadrach O, Joffe M, Adusei B, Gueye S, Fernandez P, McBride J, Andrews C, Petersen L, Lachance J. Rebbeck T, et al. Res Sq [Preprint]. 2023 Oct 12:rs.3.rs-3378303. doi: 10.21203/rs.3.rs-3378303/v1. Res Sq. 2023. Update in: Nat Genet. 2024 Oct;56(10):2093-2103. doi: 10.1038/s41588-024-01931-3. PMID: 37886553 Free PMC article. Updated. Preprint.

References

1. Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021). - PubMed
1. McHugh, J. et al. Prostate cancer risk in men of differing genetic ancestry and approaches to disease screening and management in these groups. Br. J. Cancer 126, 1366–1373 (2022). - PubMed
1. Rebbeck, T. R. Prostate cancer disparities by race and ethnicity: from nucleotide to neighborhood. Cold Spring Harb. Perspect. Med. 8, a030387 (2018). - PubMed - PMC
1. Smith, Z. L., Eggener, S. E. & Murphy, A. B. African-American prostate cancer disparities. Curr. Urol. Rep. 18, 81 (2017). - PubMed
1. Surveillance Research Program, National Cancer Institute. SEER* explorer: an interactive website for SEER cancer statistics. seer.cancer.gov/statistics-network/explorer/ (2024).

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

R35GM133727/U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa

Affiliations

Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa

Authors

Affiliations

Abstract

Update of

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical