期刊
HUMAN GENETICS
卷 132, 期 1, 页码 5-14出版社
SPRINGER
DOI: 10.1007/s00439-012-1229-4
关键词
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资金
- National Institutes of Health [U01 CA89600]
- NIH [R01 CA79596, R01 CA079596-10-S1, R01 CA136621, P50 CA69568]
- University of Utah Huntsman Cancer Institute
- Fred Hutchinson Cancer Research Center
- National Human Genome Research Institute
- CR-UK grant [C5047/A7357]
- NIHR
- Royal Marsden NHS Foundation Trust and Prostate Action
- Cancer Research UK
- European Commission [223175]
- Swedish Cancer Society
- Umea University Hospital, Umea, Sweden
- Pirkanmaa Hospital District [9M094]
- Finnish Cancer Organisations
- Sigrid Juselius Foundation
- Academy of Finland [116437, 251074]
- Cancer Council Victoria, Tattersalls
- The Whitten Foundation
- Robert H Lurie Comprehensive Cancer Center
- Urological Research Foundation
- NCI [CA119069, CA129684]
- Cancer Research UK [15007, 11022, 10118] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10096] Funding Source: researchfish
- NATIONAL CANCER INSTITUTE [U01CA089600, R01CA079596, R01CA136621, R01CA119069, P30CA042014, R25CA092049, R01CA129684, P50CA069568] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000150] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [ZIAHG200325, ZIAHG200331] Funding Source: NIH RePORTER
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 x 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 x 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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