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HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG).

Publication ,  Journal Article
Xu, J; Lange, EM; Lu, L; Zheng, SL; Wang, Z; Thibodeau, SN; Cannon-Albright, LA; Teerlink, CC; Camp, NJ; Johnson, AM; Zuhlke, KA; Stanford, JL ...
Published in: Hum Genet
January 2013

Prostate cancer has a strong familial component but uncovering the molecular basis for inherited susceptibility for this disease has been challenging. Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic. To examine this finding in a large international sample of prostate cancer families, we genotyped this mutation and 14 other SNPs in or flanking HOXB13 in 2,443 prostate cancer families recruited by the International Consortium for Prostate Cancer Genetics (ICPCG). At least one mutation carrier was found in 112 prostate cancer families (4.6 %), all of European descent. Within carrier families, the G84E mutation was more common in men with a diagnosis of prostate cancer (194 of 382, 51 %) than those without (42 of 137, 30 %), P = 9.9 × 10(-8) [odds ratio 4.42 (95 % confidence interval 2.56-7.64)]. A family-based association test found G84E to be significantly over-transmitted from parents to affected offspring (P = 6.5 × 10(-6)). Analysis of markers flanking the G84E mutation indicates that it resides in the same haplotype in 95 % of carriers, consistent with a founder effect. Clinical characteristics of cancers in mutation carriers included features of high-risk disease. These findings demonstrate that the HOXB13 G84E mutation is present in ~5 % of prostate cancer families, predominantly of European descent, and confirm its association with prostate cancer risk. While future studies are needed to more fully define the clinical utility of this observation, this allele and others like it could form the basis for early, targeted screening of men at elevated risk for this common, clinically heterogeneous cancer.

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Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

January 2013

Volume

132

Issue

1

Start / End Page

5 / 14

Location

Germany

Related Subject Headings

  • White People
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Mutation, Missense
  • Male
  • International Agencies
  • Humans
  • Homeodomain Proteins
  • Heterozygote
  • Germ-Line Mutation
 

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Xu, J., Lange, E. M., Lu, L., Zheng, S. L., Wang, Z., Thibodeau, S. N., … International Consortium for Prostate Cancer Genetics, . (2013). HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG). Hum Genet, 132(1), 5–14. https://doi.org/10.1007/s00439-012-1229-4
Xu, Jianfeng, Ethan M. Lange, Lingyi Lu, Siqun L. Zheng, Zhong Wang, Stephen N. Thibodeau, Lisa A. Cannon-Albright, et al. “HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG).Hum Genet 132, no. 1 (January 2013): 5–14. https://doi.org/10.1007/s00439-012-1229-4.
Xu J, Lange EM, Lu L, Zheng SL, Wang Z, Thibodeau SN, et al. HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG). Hum Genet. 2013 Jan;132(1):5–14.
Xu, Jianfeng, et al. “HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG).Hum Genet, vol. 132, no. 1, Jan. 2013, pp. 5–14. Pubmed, doi:10.1007/s00439-012-1229-4.
Xu J, Lange EM, Lu L, Zheng SL, Wang Z, Thibodeau SN, Cannon-Albright LA, Teerlink CC, Camp NJ, Johnson AM, Zuhlke KA, Stanford JL, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC, Maier C, Luedeke M, Vogel W, Schleutker J, Wahlfors T, Tammela T, Schaid D, McDonnell SK, DeRycke MS, Cancel-Tassin G, Cussenot O, Wiklund F, Grönberg H, Eeles R, Easton D, Kote-Jarai Z, Whittemore AS, Hsieh C-L, Giles GG, Hopper JL, Severi G, Catalona WJ, Mandal D, Ledet E, Foulkes WD, Hamel N, Mahle L, Moller P, Powell I, Bailey-Wilson JE, Carpten JD, Seminara D, Cooney KA, Isaacs WB, International Consortium for Prostate Cancer Genetics. HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG). Hum Genet. 2013 Jan;132(1):5–14.
Journal cover image

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

January 2013

Volume

132

Issue

1

Start / End Page

5 / 14

Location

Germany

Related Subject Headings

  • White People
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Mutation, Missense
  • Male
  • International Agencies
  • Humans
  • Homeodomain Proteins
  • Heterozygote
  • Germ-Line Mutation