Meta-Analysis

. 2023 Jul;84(1):13-21.

doi: 10.1016/j.eururo.2023.01.022. Epub 2023 Mar 3.

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Fei Chen¹, Ravi K Madduri², Alex A Rodriguez², Burcu F Darst³, Alisha Chou¹, Xin Sheng¹, Anqi Wang¹, Jiayi Shen¹, Edward J Saunders⁴, Suhn K Rhie⁵, Jeannette T Bensen⁶, Sue A Ingles¹, Rick A Kittles⁷, Sara S Strom⁸, Benjamin A Rybicki⁹, Barbara Nemesure¹⁰, William B Isaacs¹¹, Janet L Stanford¹², Wei Zheng¹³, Maureen Sanderson¹⁴, Esther M John¹⁵, Jong Y Park¹⁶, Jianfeng Xu¹⁷, Ying Wang¹⁸, Sonja I Berndt¹⁹, Chad D Huff⁸, Edward D Yeboah²⁰, Yao Tettey²¹, Joseph Lachance²², Wei Tang²³, Christopher T Rentsch²⁴, Kelly Cho²⁵, Benjamin H Mcmahon²⁶, Richard B Biritwum²⁷, Andrew A Adjei²⁸, Evelyn Tay²⁷, Ann Truelove²⁹, Shelley Niwa²⁹, Thomas A Sellers¹⁶, Kosj Yamoah³⁰, Adam B Murphy³¹, Dana C Crawford³², Alpa V Patel¹⁸, William S Bush³², Melinda C Aldrich³³, Olivier Cussenot³⁴, Gyorgy Petrovics³⁵, Jennifer Cullen³⁶, Christine M Neslund-Dudas⁹, Mariana C Stern¹, Zsofia Kote-Jarai⁴, Koveela Govindasami⁴, Michael B Cook¹⁹, Anand P Chokkalingam³⁷, Ann W Hsing¹⁵, Phyllis J Goodman³⁸, Thomas J Hoffmann³⁹, Bettina F Drake⁴⁰, Jennifer J Hu⁴¹, Jacob M Keaton⁴², Jacklyn N Hellwege⁴³, Peter E Clark⁴⁴, Mohamed Jalloh⁴⁵, Serigne M Gueye⁴⁵, Lamine Niang⁴⁵, Olufemi Ogunbiyi⁴⁶, Michael O Idowu⁴⁶, Olufemi Popoola⁴⁶, Akindele O Adebiyi⁴⁶, Oseremen I Aisuodionoe-Shadrach⁴⁷, Hafees O Ajibola⁴⁷, Mustapha A Jamda⁴⁷, Olabode P Oluwole⁴⁷, Maxwell Nwegbu⁴⁷, Ben Adusei⁴⁸, Sunny Mante⁴⁸, Afua Darkwa-Abrahams²⁷, James E Mensah²⁷, Halimatou Diop⁴⁹, Stephen K Van Den Eeden⁵⁰, Pascal Blanchet⁵¹, Jay H Fowke⁵², Graham Casey⁵³, Anselm J Hennis¹⁰, Alexander Lubwama⁵⁴, Ian M Thompson Jr⁵⁵, Robin Leach⁵⁶, Douglas F Easton⁵⁷, Michael H Preuss⁵⁸, Ruth J Loos⁵⁸, Susan M Gundell¹, Peggy Wan¹, James L Mohler⁵⁹, Elizabeth T Fontham⁶⁰, Gary J Smith⁶¹, Jack A Taylor⁶², Shiv Srivastava⁶³, Rosaline A Eeles⁶⁴, John D Carpten⁶⁵, Adam S Kibel⁶⁶, Luc Multigner⁶⁷, Marie-Élise Parent⁶⁸, Florence Menegaux⁶⁹, Geraldine Cancel-Tassin³⁴, Eric A Klein⁷⁰, Caroline Andrews⁷¹, Timothy R Rebbeck⁷², Laurent Brureau⁵¹, Stefan Ambs²³, Todd L Edwards¹³, Stephen Watya⁵⁴, Stephen J Chanock¹⁹, John S Witte⁷³, William J Blot⁷⁴, J Michael Gaziano⁷⁵, Amy C Justice⁷⁶, David V Conti¹, Christopher A Haiman⁷⁷

Affiliations

¹ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
² Argonne National Laboratory, Lemont, IL, USA.
³ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁴ The Institute of Cancer Research, London, UK.
⁵ Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷ Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
⁸ Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
⁹ Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
¹⁰ Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, USA.
¹¹ James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA.
¹² Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹³ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁴ Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA.
¹⁵ Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
¹⁶ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
¹⁷ Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
¹⁸ Department of Population Science, American Cancer Society, Kennesaw, GA, USA.
¹⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
²⁰ University of Ghana Medical School, Accra, Ghana.
²¹ Department of Pathology, University of Ghana, Accra, Ghana; Korle Bu Teaching Hospital, Accra, Ghana.
²² School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
²³ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
²⁴ Yale School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
²⁵ Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Jamaica Plain, MA, USA.
²⁶ Theoretical Biology Division, Los Alamos National Lab, Los Alamos, NM, USA.
²⁷ Korle Bu Teaching Hospital, Accra, Ghana.
²⁸ Department of Pathology, University of Ghana Medical School, Accra, Ghana.
²⁹ Westat, Rockville, MD, USA.
³⁰ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA; Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.
³¹ Department of Urology, Northwestern University, Chicago, IL, USA.
³² Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
³³ Division of Epidemiology, Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
³⁴ Department of Urology and Predictive Onco-Urology Group, Sorbonne Université, GRC 5 Predictive Onco-Urology, APHP-Sorbonne Université, Paris, France; CeRePP, Tenon Hospital, Paris, France.
³⁵ Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
³⁶ Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
³⁷ School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
³⁸ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³⁹ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
⁴⁰ Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA.
⁴¹ The University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
⁴² Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
⁴³ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Division of Genetic Medicine, Department of Medicine, Vanderbilt Genetics Institute, Nashville, TN, USA.
⁴⁴ Atrium Health/Levine Cancer Institute, Charlotte, NC, USA.
⁴⁵ Hôpital Général Idrissa Pouye, Dakar, Senegal.
⁴⁶ College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria.
⁴⁷ College of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, Nigeria.
⁴⁸ 37 Military Hospital, Accra, Ghana.
⁴⁹ Laboratoires Bacteriologie et Virologie, Hôpital Aristide Le Dantec, Dakar, Senegal.
⁵⁰ Division of Research, Kaiser Permanente, Northern California, Oakland, CA, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
⁵¹ CHU de Pointe-à-Pitre, Univ Antilles, Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), Pointe-à-Pitre, Guadeloupe, France.
⁵² Department of Preventive Medicine, Division of Epidemiology, The University of Tennessee Health Science Center, Memphis, TN, USA.
⁵³ Department of Public Health Science, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁵⁴ Uro Care, Kampala, Uganda.
⁵⁵ CHRISTUS Santa Rosa Medical Center Hospital, San Antonio, TX, USA.
⁵⁶ Department of Urology, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁵⁷ Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
⁵⁸ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵⁹ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁶⁰ School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
⁶¹ Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁶² Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
⁶³ Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
⁶⁴ The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK.
⁶⁵ Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶⁶ Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶⁷ Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), Rennes, France.
⁶⁸ Epidemiology and Biostatistics Unit, Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique, Laval, QC, Canada.
⁶⁹ Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif Cédex, France; Paris-Sud University, Villejuif Cédex, France.
⁷⁰ Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
⁷¹ Harvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA; Glickman Urological & Kidney Institute, Cleveland, OH, USA.
⁷² Harvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA.
⁷³ Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
⁷⁴ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; International Epidemiology Institute, Rockville, MD, USA.
⁷⁵ Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA.
⁷⁶ Yale School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA.
⁷⁷ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: haiman@usc.edu.

PMID: 36872133
PMCID: PMC10424812
DOI: 10.1016/j.eururo.2023.01.022

Meta-Analysis

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Fei Chen et al. Eur Urol. 2023 Jul.

. 2023 Jul;84(1):13-21.

doi: 10.1016/j.eururo.2023.01.022. Epub 2023 Mar 3.

Authors

Affiliations

¹ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
² Argonne National Laboratory, Lemont, IL, USA.
³ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁴ The Institute of Cancer Research, London, UK.
⁵ Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷ Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
⁸ Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
⁹ Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
¹⁰ Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, USA.
¹¹ James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA.
¹² Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹³ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁴ Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA.
¹⁵ Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
¹⁶ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
¹⁷ Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
¹⁸ Department of Population Science, American Cancer Society, Kennesaw, GA, USA.
¹⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
²⁰ University of Ghana Medical School, Accra, Ghana.
²¹ Department of Pathology, University of Ghana, Accra, Ghana; Korle Bu Teaching Hospital, Accra, Ghana.
²² School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
²³ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
²⁴ Yale School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
²⁵ Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Jamaica Plain, MA, USA.
²⁶ Theoretical Biology Division, Los Alamos National Lab, Los Alamos, NM, USA.
²⁷ Korle Bu Teaching Hospital, Accra, Ghana.
²⁸ Department of Pathology, University of Ghana Medical School, Accra, Ghana.
²⁹ Westat, Rockville, MD, USA.
³⁰ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA; Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.
³¹ Department of Urology, Northwestern University, Chicago, IL, USA.
³² Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
³³ Division of Epidemiology, Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
³⁴ Department of Urology and Predictive Onco-Urology Group, Sorbonne Université, GRC 5 Predictive Onco-Urology, APHP-Sorbonne Université, Paris, France; CeRePP, Tenon Hospital, Paris, France.
³⁵ Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
³⁶ Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
³⁷ School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
³⁸ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³⁹ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
⁴⁰ Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA.
⁴¹ The University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
⁴² Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
⁴³ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Division of Genetic Medicine, Department of Medicine, Vanderbilt Genetics Institute, Nashville, TN, USA.
⁴⁴ Atrium Health/Levine Cancer Institute, Charlotte, NC, USA.
⁴⁵ Hôpital Général Idrissa Pouye, Dakar, Senegal.
⁴⁶ College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria.
⁴⁷ College of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, Nigeria.
⁴⁸ 37 Military Hospital, Accra, Ghana.
⁴⁹ Laboratoires Bacteriologie et Virologie, Hôpital Aristide Le Dantec, Dakar, Senegal.
⁵⁰ Division of Research, Kaiser Permanente, Northern California, Oakland, CA, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
⁵¹ CHU de Pointe-à-Pitre, Univ Antilles, Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), Pointe-à-Pitre, Guadeloupe, France.
⁵² Department of Preventive Medicine, Division of Epidemiology, The University of Tennessee Health Science Center, Memphis, TN, USA.
⁵³ Department of Public Health Science, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁵⁴ Uro Care, Kampala, Uganda.
⁵⁵ CHRISTUS Santa Rosa Medical Center Hospital, San Antonio, TX, USA.
⁵⁶ Department of Urology, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁵⁷ Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
⁵⁸ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵⁹ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁶⁰ School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
⁶¹ Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁶² Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
⁶³ Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
⁶⁴ The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK.
⁶⁵ Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶⁶ Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶⁷ Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), Rennes, France.
⁶⁸ Epidemiology and Biostatistics Unit, Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique, Laval, QC, Canada.
⁶⁹ Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif Cédex, France; Paris-Sud University, Villejuif Cédex, France.
⁷⁰ Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
⁷¹ Harvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA; Glickman Urological & Kidney Institute, Cleveland, OH, USA.
⁷² Harvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA.
⁷³ Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
⁷⁴ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; International Epidemiology Institute, Rockville, MD, USA.
⁷⁵ Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA.
⁷⁶ Yale School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA.
⁷⁷ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: haiman@usc.edu.

PMID: 36872133
PMCID: PMC10424812
DOI: 10.1016/j.eururo.2023.01.022

Abstract

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

Design, setting, and participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

Outcome measurements and statistical analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.

Results and limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10^-4).

Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry.

Patient summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.

Keywords: African ancestry; Aggressive prostate cancer; Polygenic risk score; Prostate cancer; Susceptibility loci.

PubMed Disclaimer

Figures

**Fig. 1 –**
Genome-wide associations with prostate cancer risk. The association for each variant was estimated in each study/consortium and meta-analyzed across studies using a fixed-effect inverse-variance-weighted method. The nine novel association signals are highlighted in orange. The known risk associations are not shown in this plot. The dash line represents the genome-wide significance at p < 5 × 10 ^–8.

**Fig. 2 –**
Association of the multiancestry PRS with aggressive and nonaggressive forms of prostate cancer. Association was assessed comparing prostate cancer cases by Gleason score, tumor stage, and metastatic or fatal prostate cancer with controls. Results were obtained from each individual study and then meta-analyzed across studies. The x axis indicates the PRS category. The y axis indicates the ORs, with error bars representing the 95% CIs for each PRS category compared with the 40–60% PRS category. The dotted horizontal line corresponds to an OR of 1. ORs and 95% CIs for each PRS decile and/or strata are provided in Supplementary Tables 13 and 15. CI = confidence interval; OR = odds ratio; PRS = polygenic risk score.

See this image and copyright information in PMC

Comment in

Common Genetic Variants Associated with Prostate Cancer Risk: The Need for African Inclusion.
Soh PXY, Hayes VM. Soh PXY, et al. Eur Urol. 2023 Jul;84(1):22-24. doi: 10.1016/j.eururo.2023.04.006. Epub 2023 Apr 24. Eur Urol. 2023. PMID: 37100647 No abstract available.

References

1. Conti DV, Darst BF, Moss LC, et al. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nat Genet 2021;53:65–75. - PMC - PubMed
1. Dadaev T, Saunders EJ, Newcombe PJ, et al. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants. Nat Commun 2018;9:2256. - PMC - PubMed
1. Schumacher FR, Al Olama AA, Berndt SI, et al. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nat Genet 2018;50:928–36. - PMC - PubMed
1. Eeles RA, Olama AAA, Benlloch S, et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet 2013;45:385–91, 391e1–2. - PMC - PubMed
1. Al Olama AA, Kote-Jarai Z, Berndt SI, et al. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet 2014;46:1103–9. - PMC - PubMed

Publication types

Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- ClinicalTrials.gov
- 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

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Affiliations

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Authors

Affiliations

Abstract

Figures

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical