| Literature DB >> 35031163 |
Burcu F Darst1, Raymond Hughley2, Aaron Pfennig3, Ujani Hazra3, Caoqi Fan4, Peggy Wan2, Xin Sheng2, Lucy Xia2, Caroline Andrews5, Fei Chen2, Sonja I Berndt6, Zsofia Kote-Jarai7, Koveela Govindasami8, Jeannette T Bensen9, Sue A Ingles10, Benjamin A Rybicki11, Barbara Nemesure12, Esther M John13, Jay H Fowke14, Chad D Huff15, Sara S Strom15, William B Isaacs16, Jong Y Park17, Wei Zheng18, Elaine A Ostrander19, Patrick C Walsh16, John Carpten20, Thomas A Sellers17, Kosj Yamoah21, Adam B Murphy22, Maureen Sanderson23, Dana C Crawford24, Susan M Gapstur25, William S Bush24, Melinda C Aldrich26, Olivier Cussenot27, Gyorgy Petrovics28, Jennifer Cullen29, Christine Neslund-Dudas11, Rick A Kittles30, Jianfeng Xu31, Mariana C Stern10, Anand P Chokkalingam32, Luc Multigner33, Marie-Elise Parent34, Florence Menegaux35, Geraldine Cancel-Tassin27, Adam S Kibel36, Eric A Klein37, Phyllis J Goodman38, Janet L Stanford39, Bettina F Drake40, Jennifer J Hu41, Peter E Clark42, Pascal Blanchet43, Graham Casey44, Anselm J M Hennis45, Alexander Lubwama46, Ian M Thompson47, Robin J Leach48, Susan M Gundell2, Loreall Pooler2, James L Mohler49, Elizabeth T H Fontham50, Gary J Smith51, Jack A Taylor52, Laurent Brureau43, William J Blot18, Richard Biritwum53, Evelyn Tay53, Ann Truelove54, Shelley Niwa54, Yao Tettey55, Rohit Varma56, Roberta McKean-Cowdin10, Mina Torres56, Mohamed Jalloh57, Serigne Magueye Gueye57, Lamine Niang57, Olufemi Ogunbiyi58, Michael Oladimeji Idowu59, Olufemi Popoola58, Akindele O Adebiyi58, Oseremen I Aisuodionoe-Shadrach60, Maxwell Nwegbu60, Ben Adusei61, Sunny Mante61, Afua Darkwa-Abrahams53, Edward D Yeboah55, James E Mensah53, Andrew Anthony Adjei53, Halimatou Diop62, Michael B Cook6, Stephen J Chanock6, Stephen Watya63, Rosalind A Eeles8, Charleston W K Chiang4, Joseph Lachance3, Timothy R Rebbeck5, David V Conti10, Christopher A Haiman64.
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. PATIENTEntities:
Keywords: African ancestry; Allelic age; Genetics; HOXB13; Health disparities; Prostate cancer; Rare genetic variants
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Year: 2022 PMID： 35031163 PMCID： PMC9018520 DOI： 10.1016/j.eururo.2021.12.023
Source DB: PubMed Journal: Eur Urol ISSN： 0302-2838 Impact factor: 24.267