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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-01

AUTHORS

Jianfeng Xu, Ethan M. Lange, Lingyi Lu, Siqun L. Zheng, Zhong Wang, Stephen N. Thibodeau, Lisa A. Cannon-Albright, Craig C. Teerlink, Nicola J. Camp, Anna M. Johnson, Kimberly A. Zuhlke, Janet L. Stanford, Elaine A. Ostrander, Kathleen E. Wiley, Sarah D. Isaacs, Patrick C. Walsh, Christiane Maier, Manuel Luedeke, Walther Vogel, Johanna Schleutker, Tiina Wahlfors, Teuvo Tammela, Daniel Schaid, Shannon K. McDonnell, Melissa S. DeRycke, Geraldine Cancel-Tassin, Olivier Cussenot, Fredrik Wiklund, Henrik Grönberg, Ros Eeles, Doug Easton, Zsofia Kote-Jarai, Alice S. Whittemore, Chih-Lin Hsieh, Graham G. Giles, John L. Hopper, Gianluca Severi, William J. Catalona, Diptasri Mandal, Elisa Ledet, William D. Foulkes, Nancy Hamel, Lovise Mahle, Pal Moller, Isaac Powell, Joan E. Bailey-Wilson, John D. Carpten, Daniela Seminara, Kathleen A. Cooney, William B. Isaacs, International Consortium for Prostate Cancer Genetics

ABSTRACT

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. More... »

PAGES

5-14

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00439-012-1229-4

    DOI

    http://dx.doi.org/10.1007/s00439-012-1229-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013475727

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23064873


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