A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry

Burcu F. Darst; Raymond Hughley; Aaron Pfennig; Ujani Hazra; Caoqi Fan; Peggy Wan; Xin Sheng; Lucy Xia; Caroline Andrews; Fei Chen; Sonja I. Berndt; Zsofia Kote-Jarai; Koveela Govindasami; Jeannette T. Bensen; Sue A. Ingles; Benjamin A. Rybicki; Barbara Nemesure; Esther M. John; Jay H. Fowke; Chad D. Huff; Sara S. Strom; William B. Isaacs; Jong Y. Park; Wei Zheng; Elaine A. Ostrander; Patrick C. Walsh; 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; Gyorgy Petrovics; Jennifer Cullen; Christine Neslund-Dudas; Rick A. Kittles; Jianfeng Xu; Mariana C. Stern; Anand P. Chokkalingam; Luc Multigner; Marie-Elise Parent; Florence Menegaux; Geraldine Cancel-Tassin; Adam S. Kibel; Eric A. Klein; Phyllis J. Goodman; Janet L. Stanford; Bettina F. Drake; Jennifer J. Hu; Peter E. Clark; Pascal Blanchet; Graham Casey; Anselm J.M. Hennis; Alexander Lubwama; Ian M. Thompson; Robin J. Leach; Susan M. Gundell; Loreall Pooler; James L. Mohler; Elizabeth T.H. Fontham; Gary J. Smith; Jack A. Taylor; Laurent Brureau; William J. Blot; Richard Biritwum; Evelyn Tay; Ann Truelove; Shelley Niwa; Yao Tettey; Rohit Varma; Roberta McKean-Cowdin; Mina Torres; Mohamed Jalloh; Serigne Magueye Gueye; Lamine Niang; Olufemi Ogunbiyi; Michael Oladimeji Idowu; Olufemi Popoola; Akindele O. Adebiyi; Oseremen I. Aisuodionoe-Shadrach; Maxwell Nwegbu; Ben Adusei; Sunny Mante; Afua Darkwa-Abrahams; Edward D. Yeboah; James E. Mensah; Andrew Anthony Adjei; Halimatou Diop; Michael B. Cook; Stephen J. Chanock; Stephen Watya; Rosalind A. Eeles; Charleston W.K. Chiang; Joseph Lachance; Timothy R. Rebbeck; David V. Conti; Christopher A. Haiman

doi:10.1016/j.eururo.2021.12.023

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A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry

Journal article

Peer reviewed

A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry

Burcu F. Darst, Raymond Hughley, Aaron Pfennig, Ujani Hazra, Caoqi Fan, Peggy Wan, Xin Sheng, Lucy Xia, Caroline Andrews, Fei Chen, …

European urology, Vol.81(5), pp.458-462

2022-05

DOI: https://doi.org/10.1016/j.eururo.2021.12.023

PMID: 35031163

Appears in Miller School of Medicine - Latest Publications

Abstract

African ancestry

Allelic age

Genetics

Health disparities

HOXB13

Prostate cancer

Rare genetic variants

A rare African ancestry–specific germline deletion in HOXB13 (X285K) was associated with an increased risk of overall and advanced prostate cancer and was found only in men of West African ancestry. Men carrying this variant may benefit from earlier prostate cancer screening. 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. 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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Collaboration types: Industry collaboration; 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 Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry
Creators: Burcu F. Darst - University of Southern California
Raymond Hughley - University of Southern California
Aaron Pfennig - Georgia Institute of Technology
Ujani Hazra - Georgia Institute of Technology
Caoqi Fan - University of Southern California
Peggy Wan - University of Southern California
Xin Sheng - University of Southern California
Lucy Xia - University of Southern California
Caroline Andrews - Dana-Farber Cancer Institute
Fei Chen - University of Southern California
Sonja I. Berndt - National Cancer Institute
Zsofia Kote-Jarai - Institute of Cancer Research
Koveela Govindasami - Royal Marsden NHS Foundation Trust
Jeannette T. Bensen - University of North Carolina at Chapel Hill
Sue A. Ingles - University of Southern California
Benjamin A. Rybicki - Henry Ford Hospital
Barbara Nemesure - Stony Brook University
Esther M. John - Stanford University
Jay H. Fowke - University of Tennessee Health Science Center
Chad D. Huff - The University of Texas MD Anderson Cancer Center
Sara S. Strom - Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
William B. Isaacs - Johns Hopkins Hospital
Jong Y. Park - Moffitt Cancer Center
Wei Zheng - Vanderbilt University School of Medicine
Elaine A. Ostrander - National Human Genome Research Institute
Patrick C. Walsh - Johns Hopkins Hospital
John Carpten - Stanford University
Thomas A. Sellers - Moffitt Cancer Center
Kosj Yamoah - Moffitt Cancer Center
Adam B. Murphy - Northwestern University
Maureen Sanderson - Meharry Medical College
Dana C. Crawford - Case Western Reserve University
Susan M. Gapstur - Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
William S. Bush - Case Western Reserve University
Melinda C. Aldrich - Vanderbilt University Medical Center
Olivier Cussenot - Assistance Publique – Hôpitaux de Paris
Gyorgy Petrovics - Uniformed Services University of the Health Sciences
Jennifer Cullen - Uniformed Services University of the Health Sciences
Christine Neslund-Dudas - Henry Ford Hospital
Rick A. Kittles - City Of Hope National Medical Center
Jianfeng Xu - NorthShore University HealthSystem
Mariana C. Stern - Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Anand P. Chokkalingam - University of California, Berkeley
Luc Multigner - University of Southern California
Marie-Elise Parent - Université du Québec
Florence Menegaux - University of Paris-Sud
Geraldine Cancel-Tassin - Assistance Publique – Hôpitaux de Paris
Adam S. Kibel - Division of Urology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
Eric A. Klein - Cleveland Clinic
Phyllis J. Goodman - Fred Hutch Cancer Center
Janet L. Stanford - Fred Hutch Cancer Center
Bettina F. Drake - Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA
Jennifer J. Hu - The University of Texas MD Anderson Cancer Center
Peter E. Clark - Atrium Health/Levine Cancer Institute, Charlotte, NC, USA
Pascal Blanchet - Inserm
Graham Casey - University of Virginia
Anselm J.M. Hennis - Stony Brook University
Alexander Lubwama - Makerere University
Ian M. Thompson - CHRISTUS Santa Rosa Health System and The University of Texas Health Science Center, San Antonio, TX, USA
Robin J. Leach - Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Susan M. Gundell - Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Loreall Pooler - Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
James L. Mohler - University of North Carolina at Chapel Hill
Elizabeth T.H. Fontham - Louisiana State University Health Sciences Center New Orleans
Gary J. Smith - Roswell Park Cancer Institute
Jack A. Taylor - Triangle
Laurent Brureau - Inserm
William J. Blot - Vanderbilt University School of Medicine
Richard Biritwum - Korle Bu Teaching Hospital
Evelyn Tay - Korle Bu Teaching Hospital
Ann Truelove - University of North Carolina at Chapel Hill
Shelley Niwa - Westat
Yao Tettey - Korle Bu Teaching Hospital
Rohit Varma - Presbyterian Medical Center
Roberta McKean-Cowdin - Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Mina Torres - Presbyterian Medical Center
Mohamed Jalloh - Hôpital Général Idrissa Pouye, Dakar, Senegal
Serigne Magueye Gueye - Hôpital Général Idrissa Pouye, Dakar, Senegal
Lamine Niang - Hôpital Général Idrissa Pouye, Dakar, Senegal
Olufemi Ogunbiyi - University College Hospital, Ibadan
Michael Oladimeji Idowu - University of Ibadan
Olufemi Popoola - University College Hospital, Ibadan
Akindele O. Adebiyi - University College Hospital, Ibadan
Oseremen I. Aisuodionoe-Shadrach - College of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, Nigeria
Maxwell Nwegbu - College of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, Nigeria
Ben Adusei - Henry Ford Hospital
Sunny Mante - 37 Military Hospital
Afua Darkwa-Abrahams - Korle Bu Teaching Hospital
Edward D. Yeboah - Korle Bu Teaching Hospital
James E. Mensah - Korle Bu Teaching Hospital
Andrew Anthony Adjei - Korle Bu Teaching Hospital
Halimatou Diop - Hôpital Aristide Le Dantec
Michael B. Cook - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA
Stephen J. Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA
Stephen Watya - Makerere University
Rosalind A. Eeles - The Institute of Cancer Research, Sutton, London, UK
Charleston W.K. Chiang - Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Joseph Lachance - Georgia Institute of Technology
Timothy R. Rebbeck - Dana-Farber Cancer Institute
David V. Conti - Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Christopher A. Haiman - Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Publication Details: European urology, Vol.81(5), pp.458-462
Publisher: Elsevier B.V
Academic Unit: Miller School of Medicine; UMMG Department of Public Health Sciences Research
Language: English
Resource Type: Journal article
PMID: 35031163
Record Identifier: 991031723593502976