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

被引：34

作者：

Darst, Burcu F. ^{[1
,2
]}

Hughley, Raymond ^{[1
]}

Pfennig, Aaron ^{[3
]}

Hazra, Ujani ^{[3
]}

Fan, Caoqi ^{[1
,4
]}

Wan, Peggy ^{[1
]}

Sheng, Xin ^{[1
]}

Xia, Lucy ^{[1
]}

Andrews, Caroline ^{[5
,6
]}

Chen, Fei ^{[1
]}

Berndt, Sonja, I ^{[7
]}

Kote-Jarai, Zsofia ^{[8
]}

Govindasami, Koveela ^{[8
,9
]}

Bensen, Jeannette T. ^{[10
,11
]}

Ingles, Sue A. ^{[1
,2
]}

Rybicki, Benjamin A. ^{[12
]}

Nemesure, Barbara ^{[13
]}

John, Esther M. ^{[14
,15
]}

Fowke, Jay H. ^{[16
]}

Huff, Chad D. ^{[17
]}

Strom, Sara S. ^{[17
]}

Isaacs, William B. ^{[18
]}

Park, Jong Y. ^{[19
]}

Zheng, Wei ^{[20
]}

Ostrander, Elaine A. ^{[21
]}

Walsh, Patrick C. ^{[18
]}

Carpten, John ^{[22
]}

Sellers, Thomas A. ^{[19
]}

Yamoah, Kosj ^{[23
]}

Murphy, Adam B. ^{[24
]}

Sanderson, Maureen ^{[25
]}

Crawford, Dana C. ^{[26
]}

Gapstur, Susan M. ^{[27
]}

Bush, William S. ^{[26
]}

Aldrich, Melinda C. ^{[28
]}

Cussenot, Olivier ^{[29
,30
]}

Petrovics, Gyorgy ^{[31
]}

Cullen, Jennifer ^{[31
,32
]}

Neslund-Dudas, Christine ^{[12
]}

Kittles, Rick A. ^{[33
]}

Xu, Jianfeng ^{[34
,35
]}

Stern, Mariana C. ^{[1
,2
]}

Chokkalingam, Anand P. ^{[36
]}

Multigner, Luc ^{[37
]}

Parent, Marie-Elise ^{[38
]}

Menegaux, Florence ^{[39
]}

Cancel-Tassin, Geraldine ^{[29
,30
]}

Kibel, Adam S. ^{[40
,41
]}

Klein, Eric A. ^{[42
]}

Goodman, Phyllis J. ^{[43
]}

机构：

[1] Univ Southern Calif, Ctr Genet Epidemiol, Keck Sch Med, Dept Populat & Publ Hlth Sci, 1450 Biggy St, Los Angeles, CA 90033 USA

[2] Univ Southern Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA

[3] Georgia Inst Technol, Sch Biol Sci, Atlanta, GA 30332 USA

[4] Univ Southern Calif, Dept Quantitat & Computat Biol, Los Angeles, CA USA

[5] Dana Farber Canc Inst, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA

[6] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA

[7] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[8] Inst Canc Res, London, England

[9] Royal Marsden NHS Fdn Trust, London, England

[10] Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA

[11] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[12] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA

[13] SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA

[14] Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA 94305 USA

[15] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA

[16] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Div Epidemiol, Knoxville, TN 37996 USA

[17] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[18] Johns Hopkins Hosp & Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD USA

[19] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA

[20] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Med, Div Epidemiol,Sch Med, Nashville, TN USA

[21] NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA

[22] Univ Southern Calif, Keck Sch Med, Dept Translat Genom, Los Angeles, CA USA

[23] H Lee Moffitt Canc Ctr & Res Inst, Dept Radiat Oncol & Canc Epidemiol, Tampa, FL USA

[24] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA

[25] Meharry Med Coll, Dept Family & Community Med, Nashville, TN 37208 USA

[26] Case Western Reserve Univ, Cleveland Inst Computat Biol, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA

[27] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[28] Vanderbilt Univ Sch Med, Dept Thorac Surg, Div Epidemiol, Nashville, TN USA

[29] CeRePP, Paris, France

[30] Sorbonne Univ, Tenon Hosp, AP HP, GRC 5, Paris, France

[31] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA

[32] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA

[33] City Hope Comprehens Canc Ctr, Dept Populat Sci, Duarte, CA USA

[34] NorthShore Univ HealthSyst, Program Personalized Canc Care, Evanston, IL USA

[35] NorthShore Univ HealthSyst, Dept Surg, Evanston, IL USA

[36] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA

[37] Univ Rennes, Irset Inst Rech Sante Environm & Travail UMR S 10, EHESP, INSERM, Rennes, France

[38] Univ Quebec, Inst Natl Rech Sci, Ctr Armand Frappier Sante Biotechnol, Laval, PQ, Canada

[39] Univ Paris Saclay, Univ Paris Sud, CESP Ctr Res Epidemiol & Populat Hlth, INSERM,Team Canc Environm, Villejuif, France

[40] Brigham & Womens Hosp, Div Urol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA

[41] Washington Univ, St Louis, MO 63110 USA

[42] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA

[43] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA

[44] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[45] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA

[46] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA

[47] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA

[48] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Miami, FL 33136 USA

[49] Atrium Hlth, Levine Canc Inst, Charlotte, NC USA

[50] Univ Antilles, CHU Guadeloupe, INSERM, EHESP,Irset Inst Rech Sante Environm & Travail UM, Rennes, France

来源：

EUROPEAN UROLOGY | 2022年 / 81卷 / 05期

基金：

美国国家卫生研究院;

关键词：

African ancestry; Allelic age; Genetics; Health disparities; HOXB13; Prostate cancer; Rare genetic variants; MUTATION;

D O I：

10.1016/j.eururo.2021.12.023

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 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 x 10(-5); stage T3/T4: OR = 4.5, 95% CI = 2.0-10.0, p = 2 x 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. (C) 2022 Published by Elsevier B.V. on behalf of European Association of Urology.

引用

页码：458 / 462

页数：5

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