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HOXB13 mutation and prostate cancer: studies of siblings and aggressive disease.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Witte, John S. Mefford, Joel Plummer, Sarah J. Liu, Jinghua Cheng, Iona Klein, Eric A. Rybicki, Benjamin A. Casey, Graham
Description	Country affiliation: United States Author Affiliation: Witte JS ( Departments of Epidemiology & Biostatistics and Urology, University of California San Francisco, San Francisco, CA 94158, USA. jwitte@ucsf.edu)
Abstract	BACKGROUND: Recent work detected for the first time a high-risk prostate cancer mutation, in homeobox B13 (HOXB13) among European-Americans. METHODS: We further evaluated this G84E missense mutation (rs138213197) in two genetic association studies of prostate cancer: a family-based study of brothers and a case-control study of more aggressive disease (N = 2,665 total). We then calculated overall impact of this mutation by pooling all published studies of European-Americans. RESULTS: In our studies, the mutation was found exclusively among men with prostate cancer (carrier frequency = 1.48%) or unaffected brothers of cases carrying the mutation (frequency = 0.34%), and carrying the mutation gave an OR for disease = 4.79 (P = 0.01). The G84E mutation was more common among men with an earlier age of onset (≤55 years) or a family history of prostate cancer. We also observed for the first time an African-American case carrying the G84E mutation, although at HOXB13 both of his chromosomes were of European-American ancestry. The pooled analysis also indicated that carrying the G84E mutation results in an almost five-fold increase in risk of prostate cancer (P = 3.5 × 10(-17)), and this risk is even higher among cases with an early age of prostate cancer onset (≤55 years) or a family history of disease: a test of heterogeneity across these strata gives P < 1 × 10(-5). CONCLUSIONS: The HOXB13 mutation substantially increases risk of early onset, familial prostate cancer in European-American men. IMPACT: Testing for the G84E mutation in men with a positive family history may help distinguish those who merit more regular screening for prostate cancer.
File Format	HTM / HTML
ISSN	10559965
e-ISSN	15387755
DOI	10.1158/1055-9965.EPI-12-1154
Journal	Cancer Epidemiology Biomarkers & Prevention
Issue Number	4
Volume Number	22
Language	English
Publisher	American Association for Cancer Research
Publisher Date	2013-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cancer epidemiology Genetic Predisposition To Disease Homeodomain Proteins Genetics Mutation Prostate Pathology Prostatic Neoplasms Case-control Studies Disease Progression Neoplasm Grading Neoplasm Staging Polymerase Chain Reaction Prognosis Risk Factors Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Epidemiology Oncology

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HOXB13 Mutation and Prostate Cancer: Studies of Siblings and Aggressive Disease

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