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-Élise ORCID: https://orcid.org/0000-0002-4196-3773; Menegaux, Florence; Cancel-Tassin, Geraldine; Kibel, Adam S.; Klein, Eric A.; Goodman, Phyllis J.; Stanford, Janet L.; Drake, Bettina F.; Hu, Jennifer J.; Clark, Peter E.; Blanchet, Pascal; Casey, Graham; Hennis, Anselm J. M.; Lubwama, Alexander; Thompson, Ian M. JR; Leach, Robin; Gundell, Susan M.; Pooler, Loreall C.; Mohler, James L.; Fontham, Elizabeth; Smith, Gary J.; Taylor, Jack A.; Brureau, Laurent; Blot, William J.; Biritwum, Richard B.; 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 O.; Aisuodionoe-Shadrach, Oseremen I.; Nwegbu, Maxwell; Adusei, Ben; Mante, Sunny; Darkwa-Abrahams, Afua; Yeboah, Edward D.; Mensah, James E.; Anthony Adjei, Andrew; Diop, Halimatou; Cook, Micheal B.; Chanock, Stephen J.; Watya, Stephen; Eeles, Rosalind A.; Chiang, Charleston W. K.; Lachance, Joseph; Rebbeck, Timothy R.; Conti, David V. et Haiman, Christopher A. (2022). A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry European Urology , vol. 81 , nº 5. pp. 458-462. DOI: 10.1016/j.eururo.2021.12.023.

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Résumé

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.

Type de document:	Article
Mots-clés libres:	African ancestry; Allelic age; Genetics; HOXB13; Health disparities; Prostate cancer; Rare genetic variants
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	22 juin 2022 19:24
Dernière modification:	18 nov. 2022 15:15
URI:	https://espace.inrs.ca/id/eprint/12323

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