Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2011-6-21
pubmed:abstractText
Genome-wide association studies have identified prostate cancer susceptibility alleles on chromosome 11q13. As part of the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative, the region flanking the most significant marker, rs10896449, was fine mapped in 10 272 cases and 9123 controls of European origin (10 studies) using 120 common single nucleotide polymorphisms (SNPs) selected by a two-staged tagging strategy using HapMap SNPs. Single-locus analysis identified 18 SNPs below genome-wide significance (P< 10(-8)) with rs10896449 the most significant (P= 7.94 × 10(-19)). Multi-locus models that included significant SNPs sequentially identified a second association at rs12793759 [odds ratio (OR) = 1.14, P= 4.76 × 10(-5), adjusted P= 0.004] that is independent of rs10896449 and remained significant after adjustment for multiple testing within the region. rs10896438, a proxy of previously reported rs12418451 (r(2)= 0.96), independent of both rs10896449 and rs12793759 was detected (OR = 1.07, P= 5.92 × 10(-3), adjusted P= 0.054). Our observation of a recombination hotspot that separates rs10896438 from rs10896449 and rs12793759, and low linkage disequilibrium (rs10896449-rs12793759, r(2)= 0.17; rs10896449-rs10896438, r(2)= 0.10; rs12793759-rs10896438, r(2)= 0.12) corroborate our finding of three independent signals. By analysis of tagged SNPs across ?123 kb using next generation sequencing of 63 controls of European origin, 1000 Genome and HapMap data, we observed multiple surrogates for the three independent signals marked by rs10896449 (n= 31), rs10896438 (n= 24) and rs12793759 (n= 8). Our results indicate that a complex architecture underlying the common variants contributing to prostate cancer risk at 11q13. We estimate that at least 63 common variants should be considered in future studies designed to investigate the biological basis of the multiple association signals.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1460-2083
pubmed:author
pubmed-author:AlbanesDemetriusD, pubmed-author:AndrioleGerald LGL, pubmed-author:BerndtSonja ISI, pubmed-author:BolandJosephJ, pubmed-author:Cancel-TassinGeraldineG, pubmed-author:ChanockStephen JSJ, pubmed-author:ChatterjeeNilanjanN, pubmed-author:ChenQuanQ, pubmed-author:ChungCharles CCC, pubmed-author:CiampaJuliaJ, pubmed-author:CrawfordE DavidED, pubmed-author:CussenotOlivierO, pubmed-author:DiverW RyanWR, pubmed-author:FeigelsonHeather SpencerHS, pubmed-author:FraumeniJoseph FJFJr, pubmed-author:GerhardDaniela SDS, pubmed-author:Gonzalez-BosquetJesusJ, pubmed-author:GrönbergHenrikH, pubmed-author:HaimanChristopher ACA, pubmed-author:HayesRichard BRB, pubmed-author:HendersonBrian EBE, pubmed-author:HooverRobert NRN, pubmed-author:HunterDavid JDJ, pubmed-author:HutchinsonAmyA, pubmed-author:HveemKristianK, pubmed-author:IsaacsSarah DSD, pubmed-author:IsaacsWilliam BWB, pubmed-author:JacobsKevin BKB, pubmed-author:KaaksRudolfR, pubmed-author:KeyTim JTJ, pubmed-author:KolonelLaurenceL, pubmed-author:KraftPeterP, pubmed-author:Le MarchandLoicL, pubmed-author:MoaPP, pubmed-author:NjolstadIngerI, pubmed-author:OrrNickN, pubmed-author:RiboliElioE, pubmed-author:SchumacherFredrick RFR, pubmed-author:SiddiqAfshanA, pubmed-author:ThomasGillesG, pubmed-author:ThunMichael JMJ, pubmed-author:TuckerMargaretM, pubmed-author:ValeriAntoineA, pubmed-author:VattenLars JLJ, pubmed-author:VirtamoJarmoJ, pubmed-author:WacholderSholomS, pubmed-author:WeinsteinStephanieS, pubmed-author:WiklundFredrikF, pubmed-author:XuJianfengJ, pubmed-author:YeagerMeredithM
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2869-78
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Fine mapping of a region of chromosome 11q13 reveals multiple independent loci associated with risk of prostate cancer.
pubmed:affiliation
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute/NIH, 8717 Grovemont Circle, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural