HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG)
Top Cited Papers
Open Access
- 12 October 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Human Genetics
- Vol. 132 (1), 5-14
- https://doi.org/10.1007/s00439-012-1229-4
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.Keywords
This publication has 32 references indexed in Scilit:
- Germline Mutations inHOXB13and Prostate-Cancer RiskThe New England Journal of Medicine, 2012
- Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association studyNature Genetics, 2011
- Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21Nature Genetics, 2011
- Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese populationNature Genetics, 2010
- Inherited genetic variant predisposes to aggressive but not indolent prostate cancerProceedings of the National Academy of Sciences of the United States of America, 2010
- Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibilityNature Genetics, 2009
- Identification of a new prostate cancer susceptibility locus on chromosome 8q24Nature Genetics, 2009
- Evidence for two independent prostate cancer risk–associated loci in the HNF1B gene at 17q12Nature Genetics, 2008
- Two Percent of Men with Early-Onset Prostate Cancer Harbor Germline Mutations in the BRCA2 GeneAmerican Journal of Human Genetics, 2003
- Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer riskNature Genetics, 2002