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A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry.
Darst, Burcu F; Hughley, Raymond; Pfennig, Aaron; Hazra, Ujani; Fan, Caoqi; Wan, Peggy; Sheng, Xin; Xia, Lucy; Andrews, Caroline; Chen, Fei; Berndt, Sonja I; Kote-Jarai, Zsofia; Govindasami, Koveela; Bensen, Jeannette T; Ingles, Sue A; Rybicki, Benjamin A; Nemesure, Barbara; John, Esther M; Fowke, Jay H; Huff, Chad D; Strom, Sara S; Isaacs, William B; Park, Jong Y; Zheng, Wei; Ostrander, Elaine A; Walsh, Patrick C; Carpten, John; Sellers, Thomas A; Yamoah, Kosj; Murphy, Adam B; Sanderson, Maureen; Crawford, Dana C; Gapstur, Susan M; Bush, William S; Aldrich, Melinda C; Cussenot, Olivier; Petrovics, Gyorgy; Cullen, Jennifer; Neslund-Dudas, Christine; Kittles, Rick A; Xu, Jianfeng; Stern, Mariana C; Chokkalingam, Anand P; Multigner, Luc; Parent, Marie-Elise; Menegaux, Florence; Cancel-Tassin, Geraldine; Kibel, Adam S; Klein, Eric A; Goodman, Phyllis J.
Affiliation
  • Darst BF; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. Electronic address: bdarst@usc.edu.
  • Hughley R; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Pfennig A; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
  • Hazra U; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
  • Fan C; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA.
  • Wan P; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Sheng X; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Xia L; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Andrews C; Harvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA.
  • Chen F; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
  • Kote-Jarai Z; The Institute of Cancer Research, Sutton, London, UK.
  • Govindasami K; The Institute of Cancer Research, Sutton, London, UK; Royal Marsden NHS Foundation Trust, London, UK.
  • Bensen JT; 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.
  • Ingles SA; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
  • Rybicki BA; Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
  • Nemesure B; Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, USA.
  • John EM; Department of Epidemiology & Population Health and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Fowke JH; Division of Epidemiology, Department of Preventive Medicine, The University of Tennessee Health Science Center, TN, USA.
  • Huff CD; Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
  • Strom SS; Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
  • Isaacs WB; James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA.
  • Park JY; Department of Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
  • Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Ostrander EA; Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Walsh PC; James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA.
  • Carpten J; Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Sellers TA; Department of Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
  • Yamoah K; Department of Radiation Oncology and Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
  • Murphy AB; Department of Urology, Northwestern University, Chicago, IL, USA.
  • Sanderson M; Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA.
  • Crawford DC; Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Gapstur SM; Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
  • Bush WS; Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Aldrich MC; Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Cussenot O; CeRePP & Sorbonne Universite, GRC n° 5, AP-HP, Tenon Hospital, Paris, France.
  • Petrovics G; Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Cullen J; Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Neslund-Dudas C; Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
  • Kittles RA; Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • Xu J; Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
  • Stern MC; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
  • Chokkalingam AP; School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Multigner L; Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) -UMR_S 1085, Rennes, France.
  • Parent ME; Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique, University of Quebec, Laval, Quebec, Canada.
  • Menegaux F; Université Paris-Saclay, Université Paris-Sud, CESP (Center for Research in Epidemiology and Population Health), Inserm, Team Cancer-Environment, Villejuif, France.
  • Cancel-Tassin G; CeRePP & Sorbonne Universite, GRC n° 5, AP-HP, Tenon Hospital, Paris, France.
  • Kibel AS; Division of Urology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA; Washington University, St. Louis, MO, USA.
  • Klein EA; Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Goodman PJ; SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Eur Urol ; 81(5): 458-462, 2022 05.
Article in En | MEDLINE | ID: mdl-35031163
ABSTRACT
A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0-0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10-4), with greater risk observed for more aggressive and advanced disease (Gleason ≥8 odds ratio [OR] = 4.7, 95% CI = 2.3-9.5, p = 2 × 10-5; stage T3/T4 OR = 4.5, 95% CI = 2.0-10.0, p = 2 × 10-4; metastatic disease OR = 5.1, 95% CI = 1.9-13.7, p = 0.001). We estimated that the allele arose in West Africa 1500-4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. PATIENT

SUMMARY:

A rare African ancestry-specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prostatic Neoplasms / Early Detection of Cancer Type of study: Diagnostic_studies / Etiology_studies / Observational_studies / Risk_factors_studies / Screening_studies Limits: Humans / Male Language: En Journal: Eur Urol Year: 2022 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prostatic Neoplasms / Early Detection of Cancer Type of study: Diagnostic_studies / Etiology_studies / Observational_studies / Risk_factors_studies / Screening_studies Limits: Humans / Male Language: En Journal: Eur Urol Year: 2022 Document type: Article