title: Genome-wide linkage analyses of hereditary prostate cancer families with colon cancer provide further evidence for a susceptibility locus on 15q11-q14.
abstract: The search for susceptibility loci in hereditary prostate cancer (HPC) is challenging because of locus and disease heterogeneity. One approach to reduce disease heterogeneity is to stratify families on the basis of the occurrence of multiple cancer types. This method may increase the power for detecting susceptibility loci, including those with pleiotropic effects. We have completed a genome-wide SNP linkage analysis of 96 HPC families, each of which has one or more first-degree relatives with colon cancer (CCa), and further analyzed the subset of families with two or more CCa cases (n = 27). When only a prostate cancer (PCa) phenotype was considered to be affected, we observed suggestive evidence for linkage (LOD ≥1.86) at 15q14, 18q21 and 19q13 in all families, and at 1p32 and 15q11-q14 in families with two or more CCa cases. When both the PCa and CCa phenotypes were considered affected, suggestive evidence for linkage was observed at 11q25, 15q14 and 18q21 in all families, and at 1q31, 11q14 and 15q11-14 in families with two or more CCa cases. The strongest linkage signal was identified at 15q14 when both PCa and CCa phenotypes were considered to be affected in families with two or more CCa cases (recessive HLOD = 3.88). These results provide further support for the presence of HPC susceptibility loci on chromosomes 11q14, 15q11-q14 and 19q13 and highlight loci at 1q31, 11q, 15q11-14 and 18q21 as having possible pleiotropic effects. This study shows the benefit of using a comprehensive family cancer history to create more genetically homogenous subsets of HPC families for linkage analyses.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
authors.forename: Liesel M
authors.initials: LM
authors.lastname: Fitzgerald
authors.forename: Shannon K
authors.initials: SK
authors.lastname: McDonnell
authors.forename: Erin E
authors.initials: EE
authors.lastname: Carlson
authors.forename: Wendy
authors.initials: W
authors.lastname: Langeberg
authors.forename: Laura M
authors.initials: LM
authors.lastname: McIntosh
authors.forename: Kerry
authors.initials: K
authors.lastname: Deutsch
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
mesh_terms: D014408:Biomarkers, Tumor; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor
references.citation: Nat Genet. 2007 Aug;39(8):954-6
references.pmid: 17618282
references.citation: Am J Hum Genet. 1999 Mar;64(3):776-87
references.pmid: 10053012
references.citation: Eur Urol. 2007 Oct;52(4):973-82
references.pmid: 17644245
references.citation: Nature. 1995 Dec 21-28;378(6559):789-92
references.pmid: 8524414
references.citation: Nat Genet. 2007 Nov;39(11):1315-7
references.pmid: 17934461
references.citation: Exp Cell Res. 2006 Apr 15;312(7):1119-26
references.pmid: 16480715
references.citation: Nat Genet. 2008 Mar;40(3):316-21
references.pmid: 18264097
references.citation: Prostate. 2005 Sep 1;64(4):347-55
references.pmid: 15754348
references.citation: Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):4015-21
references.pmid: 15217933
references.citation: Cancer. 1990 May 1;65(9):2091-100
references.pmid: 2372775
references.citation: Annu Rev Genomics Hum Genet. 2004;5:151-75
references.pmid: 15485346
references.citation: Eur J Cancer Prev. 1994 Jul;3(4):321-7
references.pmid: 7950886
references.citation: J Natl Cancer Inst. 2006 Jan 4;98(1):61-8
references.pmid: 16391372
references.citation: Int J Cancer. 1998 Oct 29;78(3):293-7
references.pmid: 9766560
references.citation: Trends Cell Biol. 2003 Aug;13(8):435-46
references.pmid: 12888296
references.citation: Gut. 2006 Mar;55(3):362-6
references.pmid: 16150854
references.citation: Eur J Hum Genet. 2000 Mar;8(3):181-6
references.pmid: 10780783
references.citation: Hum Mol Genet. 2009 May 15;18(10):1839-48
references.pmid: 19251732
references.citation: Cell. 1996 Feb 23;84(4):587-97
references.pmid: 8598045
references.citation: Am J Hum Genet. 2000 Mar;66(3):933-44
references.pmid: 10712208
references.citation: Nat Genet. 2007 Aug;39(8):984-8
references.pmid: 17618284
references.citation: Prostate. 2006 Feb 15;66(3):317-25
references.pmid: 16245279
references.citation: Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R103-21
references.pmid: 14749351
references.citation: Hum Genet. 2006 Nov;120(4):471-85
references.pmid: 16932970
references.citation: J Med Genet. 2000 Dec;37(12):947-9
references.pmid: 11186936
references.citation: PLoS One. 2008 Aug 20;3(8):e2990
references.pmid: 18714356
references.citation: Am J Hum Genet. 2003 Mar;72(3):759-62
references.pmid: 12563560
references.citation: J Urol. 2008 May;179(5):2020-4
references.pmid: 18355840
references.citation: Am J Hum Genet. 1997 Nov;61(5):1179-88
references.pmid: 9345087
references.citation: Am J Hum Genet. 2004 Jan;74(1):106-20
references.pmid: 14681826
references.citation: Gastroenterology. 1999 Apr;116(4):789-95
references.pmid: 10092300
references.citation: Am J Hum Genet. 2008 Mar;82(3):723-36
references.pmid: 18313025
references.citation: Prostate. 2003 Dec 1;57(4):298-308
references.pmid: 14601026
references.citation: Hum Hered. 2004;57(4):172-8
references.pmid: 15583422
references.citation: Int J Gastrointest Cancer. 2003;34(1):49-54
references.pmid: 15235135
references.citation: Nat Genet. 2002 Jan;30(1):97-101
references.pmid: 11731797
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):616-21
references.pmid: 19155440
references.citation: Cancer Res. 2005 Feb 1;65(3):805-14
references.pmid: 15705877
references.citation: Prostate. 2005 Sep 1;64(4):356-61
references.pmid: 15754351
references.citation: Nat Genet. 2008 Jan;40(1):26-8
references.pmid: 18084292
references.citation: Nat Genet. 1995 Nov;11(3):241-7
references.pmid: 7581446
references.citation: Prostate. 2003 Dec 1;57(4):309-19
references.pmid: 14601027
references.citation: Genes Chromosomes Cancer. 1997 Oct;20(2):140-7
references.pmid: 9331564
references.citation: Int J Cancer. 2008 Sep 1;123(5):1141-5
references.pmid: 18546265
references.citation: Prostate. 2003 Dec 1;57(4):280-9
references.pmid: 14601024
references.citation: Am J Hum Genet. 2005 Nov;77(5):754-67
references.pmid: 16252236
references.citation: Prostate. 2007 Mar 1;67(4):410-5
references.pmid: 17192958
references.citation: J Hum Genet. 2004;49(1):9-15
references.pmid: 14666403
references.citation: Prostate. 2007 May 15;67(7):732-42
references.pmid: 17372923
references.citation: Science. 1994 Oct 7;266(5182):66-71
references.pmid: 7545954
references.citation: Science. 1997 Nov 7;278(5340):1043-50
references.pmid: 9353177
references.citation: Eur J Hum Genet. 2005 Mar;13(3):352-60
references.pmid: 15536476
references.citation: Science. 1990 Dec 21;250(4988):1684-9
references.pmid: 2270482
references.citation: J Epidemiol Community Health. 2006 Jul;60(7):593-9
references.pmid: 16790831
references.citation: Lancet. 1995 Aug 26;346(8974):544-5
references.pmid: 7658781
references.citation: Nat Genet. 2006 Jun;38(6):652-8
references.pmid: 16682969
references.citation: Am J Hum Genet. 2005 Aug;77(2):219-29
references.pmid: 15988677