Authors

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, Henry Ford Health SystemFollow
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, Henry Ford Health SystemFollow
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

Document Type

Article

Publication Date

1-11-2022

Publication Title

European urology

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.

PubMed ID

35031163

ePublication

ePub ahead of print

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