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Germline mutations in HOXB13 and prostate-cancer risk.

Publication ,  Journal Article
Ewing, CM; Ray, AM; Lange, EM; Zuhlke, KA; Robbins, CM; Tembe, WD; Wiley, KE; Isaacs, SD; Johng, D; Wang, Y; Bizon, C; Yan, G; Gielzak, M ...
Published in: N Engl J Med
January 12, 2012

BACKGROUND: Family history is a significant risk factor for prostate cancer, although the molecular basis for this association is poorly understood. Linkage studies have implicated chromosome 17q21-22 as a possible location of a prostate-cancer susceptibility gene. METHODS: We screened more than 200 genes in the 17q21-22 region by sequencing germline DNA from 94 unrelated patients with prostate cancer from families selected for linkage to the candidate region. We tested family members, additional case subjects, and control subjects to characterize the frequency of the identified mutations. RESULTS: Probands from four families were discovered to have a rare but recurrent mutation (G84E) in HOXB13 (rs138213197), a homeobox transcription factor gene that is important in prostate development. All 18 men with prostate cancer and available DNA in these four families carried the mutation. The carrier rate of the G84E mutation was increased by a factor of approximately 20 in 5083 unrelated subjects of European descent who had prostate cancer, with the mutation found in 72 subjects (1.4%), as compared with 1 in 1401 control subjects (0.1%) (P=8.5x10(-7)). The mutation was significantly more common in men with early-onset, familial prostate cancer (3.1%) than in those with late-onset, nonfamilial prostate cancer (0.6%) (P=2.0x10(-6)). CONCLUSIONS: The novel HOXB13 G84E variant is associated with a significantly increased risk of hereditary prostate cancer. Although the variant accounts for a small fraction of all prostate cancers, this finding has implications for prostate-cancer risk assessment and may provide new mechanistic insights into this common cancer. (Funded by the National Institutes of Health and others.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

January 12, 2012

Volume

366

Issue

2

Start / End Page

141 / 149

Location

United States

Related Subject Headings

  • Sequence Analysis, DNA
  • Prostatic Neoplasms
  • Prostate
  • Pedigree
  • Middle Aged
  • Male
  • Humans
  • Homeodomain Proteins
  • High-Throughput Nucleotide Sequencing
  • Germ-Line Mutation
 

Citation

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Ewing, C. M., Ray, A. M., Lange, E. M., Zuhlke, K. A., Robbins, C. M., Tembe, W. D., … Cooney, K. A. (2012). Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med, 366(2), 141–149. https://doi.org/10.1056/NEJMoa1110000
Ewing, Charles M., Anna M. Ray, Ethan M. Lange, Kimberly A. Zuhlke, Christiane M. Robbins, Waibhav D. Tembe, Kathleen E. Wiley, et al. “Germline mutations in HOXB13 and prostate-cancer risk.N Engl J Med 366, no. 2 (January 12, 2012): 141–49. https://doi.org/10.1056/NEJMoa1110000.
Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, et al. Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med. 2012 Jan 12;366(2):141–9.
Ewing, Charles M., et al. “Germline mutations in HOXB13 and prostate-cancer risk.N Engl J Med, vol. 366, no. 2, Jan. 2012, pp. 141–49. Pubmed, doi:10.1056/NEJMoa1110000.
Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, Wiley KE, Isaacs SD, Johng D, Wang Y, Bizon C, Yan G, Gielzak M, Partin AW, Shanmugam V, Izatt T, Sinari S, Craig DW, Zheng SL, Walsh PC, Montie JE, Xu J, Carpten JD, Isaacs WB, Cooney KA. Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med. 2012 Jan 12;366(2):141–149.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

January 12, 2012

Volume

366

Issue

2

Start / End Page

141 / 149

Location

United States

Related Subject Headings

  • Sequence Analysis, DNA
  • Prostatic Neoplasms
  • Prostate
  • Pedigree
  • Middle Aged
  • Male
  • Humans
  • Homeodomain Proteins
  • High-Throughput Nucleotide Sequencing
  • Germ-Line Mutation