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Genetics and Genomics

The HOXB13 variant X285K is associated with clinical significance and early age at diagnosis in African American prostate cancer patients

British Journal of Cancer volume 126, pages 791–796 (2022)Cite this article

Subjects

Abstract

Background

Recently, a novel HOXB13 variant (X285K) was observed in men of African descent with prostate cancer (PCa) in Martinique. Little is known about this or other variants in HOXB13 which may play a role in PCa susceptibility in African-American (AA) men.

Methods

We sequenced HOXB13 in an AA population of 1048 men undergoing surgical treatment for PCa at Johns Hopkins Hospital.

Results

Seven non-synonymous germline variants were observed in the patient population. While six of these variants were seen only once, X285K was found in eight patients. In a case–case analysis, we find that carriers of this latter variant are at increased risk of clinically significant PCa (1.2% carrier rate in Gleason Score ≥7 PCa vs. 0% in Gleason Score <7 PCa, odds ratio, OR = inf; 95% Confidence Interval, 95%CI:1.05-inf, P = 0.028), as well as PCa with early age at diagnosis (2.4% carrier rate in patients <50 year vs. 0.5% carrier rate in patients ≥50 year, OR = 5.25, 95% CI:1.00–28.52, P = 0.03).

Conclusions

While this variant is rare in the AA population (~0.2% MAF), its ancestry-specific occurrence and apparent preferential association with risk for the more aggressive disease at an early age emphasizes its translational potential as an important, novel PCa susceptibility marker in the high-risk AA population.

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Data availability

The data of the study are available upon reasonable request from the corresponding author.

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Acknowledgements

The generous support from the Patrick C Walsh Hereditary Prostate Cancer program is gratefully acknowledged.

Funding

The generous support from the Patrick C Walsh Hereditary Prostate Cancer program is gratefully acknowledged. This study was supported by grants from the Department of Defense (W81XWH-16-1-0764, W81XWH-16-1-0765 and W81XWH-16-1-0766).

Author information

Authors and Affiliations

  1. Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, IL, USA

    Rong Na, Jun Wei, Lilly S. Zheng & Jianfeng Xu

  2. Duke University School of Medicine and Duke Cancer Institute, Durham, NC, USA

    Chris J. Sample & Kathleen A. Cooney

  3. Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Marta Gielzak, Sodam Choi, Daniel Rabizadeh, Patrick C. Walsh & William B. Isaacs

Authors
  1. Rong Na
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  2. Jun Wei
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  3. Chris J. Sample
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  8. Patrick C. Walsh
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  9. Lilly S. Zheng
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  11. William B. Isaacs
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Contributions

WI conceived and designed the study. RN, MG, CS, DR, KC, PW, SC and LZ contributed materials and collected the data. RN and JW analysed the data. RN, WI and JX wrote the manuscript.

Corresponding author

Correspondence to William B. Isaacs.

Ethics declarations

Competing interests

KAC and WBI are coinventors on a patent (no. 9593380; Inst.) related to the discovery of HOXB13 as a prostate cancer susceptibility gene.

Ethics approval and consent to participate

The study was approved by the Institutional Review Boards at Johns Hopkins University. The study was performed in accordance with the Declaration of Helsinki.

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All the authors have reviewed and approved the current version of the manuscript.

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Na, R., Wei, J., Sample, C.J. et al. The HOXB13 variant X285K is associated with clinical significance and early age at diagnosis in African American prostate cancer patients. Br J Cancer 126, 791–796 (2022). https://doi.org/10.1038/s41416-021-01622-4

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