| Title: |
A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry |
| Authors: |
Darst, Burcu; Hughley, Raymond; Pfennig, Aaron; Hazra, Ujani; Fan, Caoqi; Wan, Peggy; Sheng, Xin; Xia, Lucy; Andrews, Caroline; Chen, Fei; Berndt, Sonja; Kote-Jarai, Zsofia; Govindasami, Koveela; Bensen, Jeannette; Ingles, Sue; Rybicki, Benjamin; Nemesure, Barbara; John, Esther; Fowke, Jay; Huff, Chad; Strom, Sara; Isaacs, William; Park, Jong; Zheng, Wei; Ostrander, Elaine; Walsh, Patrick; Carpten, John; Sellers, Thomas; Yamoah, Kosj; Murphy, Adam; Sanderson, Maureen; Crawford, Dana; Gapstur, Susan; Bush, William; Aldrich, Melinda; Cussenot, Olivier; Petrovics, Gyorgy; Cullen, Jennifer; Neslund-Dudas, Christine; Kittles, Rick; Xu, Jianfeng; Stern, Mariana; Chokkalingam, Anand; Multigner, Luc; Parent, Marie-Elise; Menegaux, Florence; Cancel-Tassin, Geraldine; Kibel, Adam; Klein, Eric; Goodman, Phyllis; Stanford, Janet; Drake, Bettina; Hu, Jennifer; Clark, Peter; Blanchet, Pascal; Casey, Graham; Hennis, Anselm; Lubwama, Alexander; Thompson, Ian; Leach, Robin; Gundell, Susan; Pooler, Loreall; Mohler, James; Fontham, Elizabeth; Smith, Gary; Taylor, Jack; Brureau, Laurent; Blot, William; Biritwum, Richard; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Tettey, Yao; Varma, Rohit; Mckean-Cowdin, Roberta; Torres, Mina; Jalloh, Mohamed; Magueye Gueye, Serigne; Niang, Lamine; Ogunbiyi, Olufemi; Oladimeji Idowu, Michael; Popoola, Olufemi; Adebiyi, Akindele; Aisuodionoe-Shadrach, Oseremen; Nwegbu, Maxwell; Adusei, Ben; Mante, Sunny; Darkwa-Abrahams, Afua; Yeboah, Edward; Mensah, James; Anthony Adjei, Andrew; Diop, Halimatou; Cook, Michael; Chanock, Stephen; Watya, Stephen; Eeles, Rosalind; Chiang, Charleston; Lachance, Joseph; Rebbeck, Timothy; Conti, David; Haiman, Christopher; Hennis, Anselm J.M.; Fontham, Elizabeth T.H.; Chiang, Charleston W.K. |
| Contributors: |
University of Southern California (USC); The Institute of Cancer Research; Centre de Recherche pour les Pathologies Prostatiques Paris (CeRePP); Sorbonne Université (SU); Institut de recherche en santé, environnement et travail (Irset); Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Centre de recherche en épidémiologie et santé des populations (CESP); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse; AP-HP. Université Paris Saclay-AP-HP. Université Paris Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay |
| Source: |
ISSN: 0302-2838. |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2022 |
| Collection: |
Université de Versailles Saint-Quentin-en-Yvelines: HAL-UVSQ |
| Subject Terms: |
African ancestry; Allelic age; Genetics; HOXB13; Health disparities; Prostate cancer; Rare genetic variants; MESH: Case-Control Studies; MESH: Early Detection of Cancer; MESH: Genetic Predisposition to Disease; MESH: Germ Cells; MESH: Germ-Line Mutation; MESH: Homeodomain Proteins; MESH: Humans; MESH: Male; MESH: Prostate-Specific Antigen; MESH: Prostatic Neoplasms; [SDV.CAN]Life Sciences [q-bio]/Cancer |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35031163; PUBMED: 35031163; PUBMEDCENTRAL: PMC9018520 |
| DOI: |
10.1016/j.eururo.2021.12.023 |
| Availability: |
https://hal.science/hal-03789472; https://hal.science/hal-03789472v1/document; https://hal.science/hal-03789472v1/file/hal-03789472.pdf; https://doi.org/10.1016/j.eururo.2021.12.023 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.224F51C0 |
| Database: |
BASE |