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The G84E mutation of HOXB13 is associated with increased risk for prostate cancer: results from the REDUCE trial.

Authors
  • Chen, Zhuo
  • Greenwood, Celia
  • Isaacs, William B
  • Foulkes, William D
  • Sun, Jielin
  • Zheng, Sigun L
  • Condreay, Lynn D
  • Xu, Jianfeng
Type
Published Article
Journal
Carcinogenesis
Publisher
Oxford University Press
Publication Date
Jun 01, 2013
Volume
34
Issue
6
Pages
1260–1264
Identifiers
DOI: 10.1093/carcin/bgt055
PMID: 23393222
Source
Medline
License
Unknown

Abstract

A novel rare mutation, homeobox B13 (HOXB13) G84E, was reported to co-segregate with prostate cancer (PCa) in hereditary PCa families and associate with PCa risk in unrelated cases and controls. In this study, we aim to compare the G84E mutation frequency among subjects of different races/ethnicities from various geographic regions in the world and to assess its risk for developing PCa, in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. All the 3508 subjects had initial negative prostate biopsy and were biopsied at Year 2 and 4 for detection of PCa. The G84E mutation was detected only in Caucasians, with the highest carrier frequency in Northern Europe (1.06%), followed by Western Europe (0.60%) and North America (0.31%). No mutation carrier was observed in Southern Europe, Eastern Europe, Latin America, Australia and South Africa. In Caucasians, the G84E mutation frequency was 0.99% and 0.24% in positive and negative biopsy subjects, respectively (P = 0.01). In positive biopsy subjects, the frequency was significantly higher in subjects with a positive family history than those without (4.31% versus 0.34%, P = 0.002). In the 4 year follow-up, the PCa detection rate was 53.8% among the 13 mutation carriers and 22.0% among 3186 non-carriers, relative risk = 2.45 (95% confidence interval: 1.48-4.07). All mutation carriers shared a common haplotype, suggesting a founder effect. In Finland, the G84E mutation was estimated to occur in the year 1792 (95% credible interval: 1735-1831). In conclusion, the G84E mutation of HOXB13, a relatively recent mutation that likely occurred in Northern Europe, significantly increases risk for PCa.

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