Lu, L and Cancel-Tassin, G and Valeri, A and Cussenot, O and Lange, EM and Cooney, KA and Farnham, JM and Camp, NJ and Canon-Albright, LA and Tammela, TLJ and Schleutker, J and Hoegel, W and Wiklund, F and Emanuelsson, M and Gronberg, H and Wiley, KE and Isaacs, SD and Walsh, PC and Helfand, BT and Kan, D and Catalona, WJ and Stanford, JL and Fitzgerald, LM and Johanneson, B and Deutsch, K and McIntosh, L and Ostrander, EA and Thibodeau, SN and McDonnel, SK and Hebbring, S and Schaid, DJ and Whittemore, AS and Oakley-Girvan, I and Hsieh, C-L and Powell, I and Bailey-Wilson, JE and Cropp, CD and Simpson, C and Carpten, JD and Seminara, D and Zheng, SL and Xu, J and Giles, GG and Severi, G and Hopper, JL and English, DR and Foulkes, WD and Maehle, L and Moller, P and Badzioch, MD and Edwards, S and Guy, M and Eeles, R and Easton, D and Isaacs, WB, International Consortium for Prostate Cancer Genetics, Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG, The Prostate, 72, (4) pp. 410-26. ISSN 0270-4137 (2012) [Refereed Article]
Copyright 2011 Wiley Periodicals, Inc.
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, 37 cM 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 scores 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 this common cancer.
|Item Type:||Refereed Article|
|Keywords:||Prostate Cancer ICPCG|
|Research Division:||Medical and Health Sciences|
|Research Group:||Oncology and Carcinogenesis|
|Research Field:||Cancer Genetics|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Cancer and Related Disorders|
|UTAS Author:||Fitzgerald, LM (Dr Liesel Fitzgerald)|
|Web of Science® Times Cited:||8|
|Deposited By:||Menzies Institute for Medical Research|
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