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Prostate cancer genetic risk and associated aggressive disease in men of African ancestry

Author

Listed:
  • Pamela X. Y. Soh

    (University of Sydney)

  • Naledi Mmekwa

    (University of Pretoria)

  • Desiree C. Petersen

    (Stellenbosch University)

  • Kazzem Gheybi

    (University of Sydney)

  • Smit van Zyl

    (University of Limpopo)

  • Jue Jiang

    (University of Sydney)

  • Sean M. Patrick

    (University of Pretoria)

  • Raymond Campbell

    (Phulukisa health Care)

  • Weerachai Jaratlerdseri

    (University of Sydney)

  • Shingai B. A. Mutambirwa

    (Sefako Makgatho Health Science University, Dr George Mukhari Academic Hospital)

  • M. S. Riana Bornman

    (University of Pretoria)

  • Vanessa M. Hayes

    (University of Sydney
    University of Pretoria
    University of Limpopo
    University of Manchester)

Abstract

African ancestry is a significant risk factor for prostate cancer and advanced disease. Yet, genetic studies have largely been conducted outside the context of Sub-Saharan Africa, identifying 278 common risk variants contributing to a multiethnic polygenic risk score, with rare variants focused on a panel of roughly 20 pathogenic genes. Based on this knowledge, we are unable to determine polygenic risk or differentiate prostate cancer status interrogating whole genome data for 113 Black South African men. To further assess for potentially functional common and rare variant associations, here we interrogate 247,780 exomic variants for 798 Black South African men using a case versus control or aggressive versus non-aggressive study design. Notable genes of interest include HCP5, RFX6 and H3C1 for risk, and MKI67 and KLF5 for aggressive disease. Our study highlights the need for further inclusion across the African diaspora to establish African-relevant risk models aimed at reducing prostate cancer health disparities.

Suggested Citation

  • Pamela X. Y. Soh & Naledi Mmekwa & Desiree C. Petersen & Kazzem Gheybi & Smit van Zyl & Jue Jiang & Sean M. Patrick & Raymond Campbell & Weerachai Jaratlerdseri & Shingai B. A. Mutambirwa & M. S. Rian, 2023. "Prostate cancer genetic risk and associated aggressive disease in men of African ancestry," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43726-w
    DOI: 10.1038/s41467-023-43726-w
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    References listed on IDEAS

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    1. Kaivalya Walavalkar & Bharath Saravanan & Anurag Kumar Singh & Ranveer Singh Jayani & Ashwin Nair & Umer Farooq & Zubairul Islam & Deepanshu Soota & Rajat Mann & Padubidri V. Shivaprasad & Matthew L. , 2020. "A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Baotong Zhang & Yixiang Li & Qiao Wu & Lin Xie & Benjamin Barwick & Changying Fu & Xin Li & Daqing Wu & Siyuan Xia & Jing Chen & Wei Ping Qian & Lily Yang & Adeboye O. Osunkoya & Lawrence Boise & Paul, 2021. "Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    3. Julia F. Hopkins & Veronica Y. Sabelnykova & Joachim Weischenfeldt & Ronald Simon & Jennifer A. Aguiar & Rached Alkallas & Lawrence E. Heisler & Junyan Zhang & John D. Watson & Melvin L. K. Chua & Mic, 2017. "Mitochondrial mutations drive prostate cancer aggression," Nature Communications, Nature, vol. 8(1), pages 1-8, December.
    4. Weerachai Jaratlerdsiri & Jue Jiang & Tingting Gong & Sean M. Patrick & Cali Willet & Tracy Chew & Ruth J. Lyons & Anne-Maree Haynes & Gabriela Pasqualim & Melanie Louw & James G. Kench & Raymond Camp, 2022. "African-specific molecular taxonomy of prostate cancer," Nature, Nature, vol. 609(7927), pages 552-559, September.
    5. Ananyo Choudhury & Shaun Aron & Laura R. Botigué & Dhriti Sengupta & Gerrit Botha & Taoufik Bensellak & Gordon Wells & Judit Kumuthini & Daniel Shriner & Yasmina J. Fakim & Anisah W. Ghoorah & Eileen , 2020. "High-depth African genomes inform human migration and health," Nature, Nature, vol. 586(7831), pages 741-748, October.
    6. Meixia Che & Aashi Chaturvedi & Sarah A. Munro & Samuel P. Pitzen & Alex Ling & Weijie Zhang & Josh Mentzer & Sheng-Yu Ku & Loredana Puca & Yanyun Zhu & Andries M. Bergman & Tesa M. Severson & Colleen, 2021. "Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    7. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
    8. Philippe Mauffrey & Nicolas Tchitchek & Vilma Barroca & Alexis-Pierre Bemelmans & Virginie Firlej & Yves Allory & Paul-Henri Roméo & Claire Magnon, 2019. "Progenitors from the central nervous system drive neurogenesis in cancer," Nature, Nature, vol. 569(7758), pages 672-678, May.
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