A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry

Burcu F Darst; Peggy Wan; Xin Sheng; Jeannette T Bensen; Sue A Ingles; Benjamin A Rybicki; Barbara Nemesure; Esther M John; Jay H Fowke; Victoria L Stevens; Sonja I Berndt; Chad D Huff; Sara S Strom; Jong Y Park; Wei Zheng; Elaine A Ostrander; Patrick C Walsh; Shiv Srivastava; John Carpten; Thomas A Sellers; Kosj Yamoah; Adam B Murphy; Maureen Sanderson; Dana C Crawford; Susan M Gapstur; William S Bush; Melinda C Aldrich; Olivier Cussenot; Meredith Yeager; Gyorgy Petrovics; Jennifer Cullen; Christine Neslund-Dudas; Rick A Kittles; Jianfeng Xu; Mariana C Stern; Zsofia Kote-Jarai; Koveela Govindasami; Anand P Chokkalingam; Luc Multigner; Marie-Elise Parent; Florence Menegaux; Geraldine Cancel-Tassin; Adam S Kibel; Eric A Klein; Phyllis J Goodman; Bettina F Drake; Jennifer J Hu; Peter E Clark; Pascal Blanchet; Graham Casey; Anselm J.M Hennis; Alexander Lubwama; Ian M Thompson; Robin Leach; Susan M Gundell; Loreall Pooler; Lucy Xia; James L Mohler; Elizabeth T.H Fontham; Gary J Smith; Jack A Taylor; Rosalind A Eeles; Laurent Brureau; Stephen J Chanock; Stephen Watya; Janet L Stanford; Diptasri Mandal; William B Isaacs; Kathleen Cooney; William J Blot; David V Conti; Christopher A Haiman

doi:10.1016/j.eururo.2020.04.060

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A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry

Journal article

Open access

Peer reviewed

A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry

Burcu F Darst, Peggy Wan, Xin Sheng, Jeannette T Bensen, Sue A Ingles, Benjamin A Rybicki, Barbara Nemesure, Esther M John, Jay H Fowke, Victoria L Stevens, …

European urology, Vol.78(3), pp.316-320

2020-09

DOI: https://doi.org/10.1016/j.eururo.2020.04.060

PMID: 32409115

Abstract

8q24

African ancestry

Familial prostate cancer

Genetic variant

Genetics

Family history

Prostate cancer

Health disparities

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry–specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13–7.22) and 33.41 (95% CI = 10.86–102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17–25%) for TA heterozygotes and 38% (95% CI = 13–65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. We found that rs72725854, an African ancestry–specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening. The African ancestry–specific prostate cancer risk variant at 8q24, rs72725854, is enriched in men diagnosed at younger ages and men with a prostate cancer family history. Carriers of this risk allele would benefit from regular and earlier prostate cancer screening.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.189 Genome Studies; 1.189.597 BRCA1
Web Of Science research areas: Urology & Nephrology
ESI research areas: Clinical Medicine

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Title: A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry
Creators: Burcu F Darst - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Peggy Wan - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Xin Sheng - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Jeannette T Bensen - Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Sue A Ingles - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Benjamin A Rybicki - Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA
Barbara Nemesure - Department of Preventive Medicine, Stony Brook University, Stony Brook, NY, USA
Esther M John - Department of Epidemiology and Population Health and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
Jay H Fowke - Division of Epidemiology, Department of Preventive Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA
Victoria L Stevens - Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
Sonja I Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA
Chad D Huff - Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Sara S Strom - Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Jong Y Park - Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Wei Zheng - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA
Elaine A Ostrander - Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Patrick C Walsh - The James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA
Shiv Srivastava - Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
John Carpten - Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Thomas A Sellers - Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Kosj Yamoah - Department of Radiation Oncology and Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Adam B Murphy - Department of Urology, Northwestern University, Chicago, IL, USA
Maureen Sanderson - Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA
Dana C Crawford - Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA
Susan M Gapstur - Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
William S Bush - Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA
Melinda C Aldrich - Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA
Olivier Cussenot - CeRePP and Sorbonne Universite, GRC n° 5, AP-HP, Tenon Hospital, Paris, France
Meredith Yeager - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA
Gyorgy Petrovics - Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Jennifer Cullen - Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Christine Neslund-Dudas - Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA
Rick A Kittles - Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
Jianfeng Xu - Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA
Mariana C Stern - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Zsofia Kote-Jarai - The Institute of Cancer Research, Sutton, London, UK
Koveela Govindasami - Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, London, UK
Anand P Chokkalingam - School of Public Health, University of California, Berkeley, Berkeley, CA, USA
Luc Multigner - Inserm U1085—IRSET, Rennes, France
Marie-Elise Parent - INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, University of Quebec, Laval, Quebec, Canada
Florence Menegaux - INSERM, Center for Research in Epidemiology and Population Health, Team Cancer-Environment, Université Paris-Saclay, Université Paris-Sud, Villejuif, France
Geraldine Cancel-Tassin - CeRePP and Sorbonne Universite, GRC n° 5, AP-HP, Tenon Hospital, Paris, France
Adam S Kibel - Division of Urology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
Eric A Klein - Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
Phyllis J Goodman - SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Bettina F Drake - Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA
Jennifer J Hu - Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
Peter E Clark - Vanderbilt University Medical Center, Nashville, TN, USA
Pascal Blanchet - Inserm U1085—IRSET, Rennes, France
Graham Casey - Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
Anselm J.M Hennis - Department of Preventive Medicine, Stony Brook University, Stony Brook, NY, USA
Alexander Lubwama - School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda
Ian M Thompson - Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Robin Leach - Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Susan M Gundell - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Loreall Pooler - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Lucy Xia - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
James L Mohler - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Elizabeth T.H Fontham - School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA
Gary J Smith - Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA
Jack A Taylor - Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
Rosalind A Eeles - The Institute of Cancer Research, Sutton, London, UK
Laurent Brureau - Inserm U1085—IRSET, Rennes, France
Stephen J Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA
Stephen Watya - School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda
Janet L Stanford - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Diptasri Mandal - Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
William B Isaacs - The James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA
Kathleen Cooney - Department of Medicine, Duke University of Medicine, Durham, NC, USA
William J Blot - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA
David V Conti - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Christopher A Haiman - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Publication Details: European urology, Vol.78(3), pp.316-320
Publisher: Elsevier B.V
Academic Unit: Miller School of Medicine; UMMG Department of Public Health Sciences Research
Language: English
Resource Type: Journal article
PMID: 32409115
Record Identifier: 991031578334702976