期刊
PROSTATE
卷 72, 期 4, 页码 410-426出版社
WILEY-BLACKWELL
DOI: 10.1002/pros.21443
关键词
prostate cancer; hereditary; susceptibility; 8q24
资金
- National Institutes of Health [U01 CA89600]
- Cancer Research UK (CR-UK) [C5047/A3354]
- Cancer Council Victoria
- National Health and Medical Research Council [940934, 251533, 209057, 126402, 396407]
- Tattersall's and The Whitten Foundation
- NCI Post-doctoral Fellowship in Cancer Prevention [R25]
- CeRePP: Association pour la Recherche sur le Cancer [5441]
- Pirkanmaa Hospital District
- Reino Lahtikari Foundation
- Finnish Cancer Organisations
- Sigrid Juselius Foundation
- Academy of Finland [211123]
- University of Ulm Group: Deutsche Krebshilfe [70-3111-V03]
- Umea University Hospital, Umea, Sweden
- USPHS [CA90752, CA98364, CA106523]
- Utah Cancer Registry from the National Cancer Institute's Surveillance, Epidemiology [N01-PC-35141]
- Huntsman Cancer Foundation
- National Human Genome Research Institute, NIH
- Department of Defense [PC051264]
- Cancer Research UK [11022, 10588, 15007, 10118] Funding Source: researchfish
- Academy of Finland (AKA) [211123, 211123] Funding Source: Academy of Finland (AKA)
BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD?=?1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS. In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS. Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD cores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS. These results will be useful in prioritizing future susceptibility gene discovery efforts in thiscommon cancer. Prostate 72: 410-426, 2012. (C) 2011 Wiley Periodicals, Inc.
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