Evidence map›Paper›PMID 41038821›Full record

ArticleNature communications2025

Pathogenic variants reveal candidate genes for prostate cancer germline testing for men of African ancestry.

Kazzem Gheybi, Pamela X Y Soh, Jue Jiang, Tumisang M N Mbeki, Melanie Louw, Daniel Burns, Piyushkumar Mundra, Daria Kiriy, Md Mehedi Hasan, Weerachai Jaratlerdsiri and 33 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors.

Kazzem GheybiAncestry & Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.ORCID http://orcid.org/0000-0001-8557-3649
Pamela X Y SohAncestry & Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.ORCID http://orcid.org/0000-0002-8485-6556
Jue JiangAncestry & Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.ORCID http://orcid.org/0000-0003-0920-8310
Tumisang M N MbekiSchool of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Melanie LouwNational Health Laboratory Services, Johannesburg, South Africa.
Daniel BurnsThe Institute of Cancer Research, London, UK.
Piyushkumar MundraChildrens Cancer Institute, Lowy Cancer Centre, University of New South Wales Sydney, Randwick, NSW, Australia.
Daria KiriyBiotech Research & Innovation Centre & Finsen Laboratory, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Md Mehedi HasanAncestry & Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.
Weerachai JaratlerdsiriAncestry & Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.ORCID http://orcid.org/0000-0001-9100-1807
Maphuti Tebogo LebeloDepartment of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Raymond A CampbellDepartment of Urology, University of Pretoria, Pretoria, South Africa.
Mulalo B RadzumaDepartment of Urology, Sefako Makgatho Health Science University, Dr George Mukhari Academic Hospital, Medunsa, Ga-Rankuwa, South Africa.
Mukudeni NenzheleleTshilidzini Hospital, Shayandima, Thohoyandou, Limpopo, South Africa.
Muvhulawa ObidaSchool of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Martin ObidaSchool of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Winstar M OmbukiDepartment of Urology, East African Kidney Institute, University of Nairobi, Nairobi, Kenya.
Micah O OyaroDepartment of Human Pathology, University of Nairobi, Nairobi, Kenya.
Sean M PatrickSchool of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Massimo LodaDepartment of Pathology and Laboratory Medicine, Weil Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-9674-8379
David C WedgeManchester Cancer Research Centre, University of Manchester, Manchester, M20 4GJ, UK.ORCID http://orcid.org/0000-0002-7572-3196
Robert G BristowManchester Cancer Research Centre, University of Manchester, Manchester, M20 4GJ, UK.ORCID http://orcid.org/0000-0002-8553-9544
Daniel S BrewerNorwich Medical School, University of East Anglia, Norwich, UK.ORCID http://orcid.org/0000-0003-4753-9794
Colin S CooperThe Institute of Cancer Research, London, UK.
Jüri ReimandComputational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-2299-2309
Geraldine Cancel-TassinCeRePP, Hospital Tenon, Paris, France.ORCID http://orcid.org/0000-0002-9583-6382
Olivier CussenotCeRePP, Hospital Tenon, Paris, France.
Chris M HovensCollaborative Center for Genomic Cancer Medicine University of Melbourne, The Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia.
Niall M CocoranCollaborative Center for Genomic Cancer Medicine University of Melbourne, The Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia.
Phillip D StrickerSt Vincent's Prostate Cancer Research Centre, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-0934-0656
Thorsten SchlommCharité Universitätsmedizin Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0001-9557-4653
Gail S PrinsDepartment of Urology, University of Illinois at Chicago, Chicago, IL, 60612, USA.
Karina Dalsgaard SørensenDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark.ORCID http://orcid.org/0000-0002-4902-5490
Pan Prostate Cancer Group
HEROIC PCaPH Africa1K
Joachim WeischenfeldtBiotech Research & Innovation Centre & Finsen Laboratory, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-3917-5524
Shingai B A MutambirwaDepartment of Urology, Sefako Makgatho Health Science University, Dr George Mukhari Academic Hospital, Medunsa, Ga-Rankuwa, South Africa.
Peter M NgugiDepartment of Urology, East African Kidney Institute, University of Nairobi, Nairobi, Kenya.
David M ThomasCentre for Molecular Oncology, School of Biomedical Sciences, University of New South Wales Sydney, Randwick, NSW, Australia.
Zsofia Kote-JaraiThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-6329-5155
Rosalind A EelesThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-3698-6241
M S Riana BornmanSchool of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.ORCID http://orcid.org/0000-0003-3975-2333
Vanessa M HayesAncestry & Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia. vanessa.hayes@sydney.edu.au.ORCID http://orcid.org/0000-0002-4524-7280

Funding

Pilot Program CoreP30ES027792 · NIEHS · UNIVERSITY OF CHICAGO · PI Gokhan M. Mutlu, Gail S Prins · 2017 to 2026
$13.6M
Genomic bases for African geo-ethnic prostate cancer health disparityR01CA285772 · NCI · UNIVERSITY OF SYDNEY · PI Vanessa Marie Hayes · 2024 to 2026
$1.5M
Cancer Research UK (CRUK) C5047/A14835/A22530/A17528, C309/A11566, C368/A6743, A368/A7990, C14303/A17197Department of Health | National Health and Medical Research Council (NHMRC) APP1165762, APP2001098, APP2010551NCI NIH HHS R01 CA285772NIEHS NIH HHS P30 ES027792Petre Foundation Petre ChairProstate Cancer UK MA-TIA23-002United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) PC200390, PC210168, PC230673U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R01CA285772-01
6 · The paper itself

Abstract

Prostate cancer (PCa) germline testing, while gaining momentum, is ancestry restrictive and African exclusive. Through whole genome sequencing for 217 African ancestral cases (186 southern African, 31 Pan representative), we identify 172 potentially pathogenic variants in 78 DNA damage repair or PCa related genes. Prevalence for reported (13/217, 5.99%) and cumulative predicted (24/217, 11.06%) variants of significance (11 genes) falls below that reported for non-Africans. Conversely, BRCA1, HOXB13, CDK12, MLH1, MSH2, and BRIP1 remain unimpacted. Through pathogenic ranking based on variant frequency and functionality, clinical presentation and tumour-matched biallelic inactivation, top-ranked candidates include PREX2, POLE, FAT1, BRCA2, POLQ, LRP1B and ATM. Besides notable impact of DNA polymerases, including POLG, Fanconi anaemia genes include FANCD2, FANCA, FANCG, ERCC4, FANCE and FANCI, while DNA mismatch repair genes MSH3 and PMS1 outranked known namesakes MSH6 and PMS2. This study provides insights into the spectrum of African-relevant potentially pathogenic PCa variants, highlighting much-needed gene candidates for ancestry-inclusive germline testing.

Indexed as

Black PeopleGenetic Predisposition to DiseaseGerm-Line MutationProstatic NeoplasmsDNA RepairGenetic TestingHumansMaleMiddle AgedWhole Genome Sequencing

Identifiers

PMID41038821
PMCPMC12491615

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