title: Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics.
abstract: While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer. Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component. Starting with 1,233 familial prostate cancer families with genome scan data available from the International Consortium for Prostate Cancer Genetics, we selected those that had at least three members with the phenotype of clinically aggressive prostate cancer, as defined by either high tumor grade and/or stage, resulting in 166 pedigrees (13%). Genome-wide linkage data were then pooled to perform a combined linkage analysis for these families. Linkage signals reaching a suggestive level of significance were found on chromosomes 6p22.3 (LOD = 3.0), 11q14.1-14.3 (LOD = 2.4), and 20p11.21-q11.21 (LOD = 2.5). For chromosome 11, stronger evidence of linkage (LOD = 3.3) was observed among pedigrees with an average at diagnosis of 65 years or younger. Other chromosomes that showed evidence for heterogeneity in linkage across strata were chromosome 7, with the strongest linkage signal among pedigrees without male-to-male disease transmission (7q21.11, LOD = 4.1), and chromosome 21, with the strongest linkage signal among pedigrees that had African American ancestry (21q22.13-22.3; LOD = 3.2). Our findings suggest several regions that may contain genes which, when mutated, predispose men to develop a more aggressive prostate cancer phenotype. This provides a basis for attempts to identify these genes, with potential clinical utility for men with aggressive prostate cancer and their relatives.
authors.affiliation: Harwick 7, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. schaid@mayo.edu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.forename: Shannon K
authors.initials: SK
authors.lastname: McDonnell
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Zarfas
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Scott
authors.initials: S
authors.lastname: Hebbring
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Lovise
authors.initials: L
authors.lastname: Mahle
authors.forename: Pal
authors.initials: P
authors.lastname: Moller
authors.forename: Michael
authors.initials: M
authors.lastname: Badzioch
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Chris
authors.initials: C
authors.lastname: Evans
authors.forename: Steve
authors.initials: S
authors.lastname: Edwards
authors.forename: Julia
authors.initials: J
authors.lastname: Meitz
authors.forename: Sarah
authors.initials: S
authors.lastname: Bullock
authors.forename: Questa
authors.initials: Q
authors.lastname: Hope
authors.forename: Michelle
authors.initials: M
authors.lastname: Guy
authors.forename: Chih-lin
authors.initials: CL
authors.lastname: Hsieh
authors.forename: Jerry
authors.initials: J
authors.lastname: Halpern
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Balise
authors.forename: Ingrid
authors.initials: I
authors.lastname: Oakley-Girvan
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Latchezar
authors.initials: L
authors.lastname: Dimitrov
authors.forename: Bao-Li
authors.initials: BL
authors.lastname: Chang
authors.forename: Tamara S
authors.initials: TS
authors.lastname: Adams
authors.forename: Aubrey R
authors.initials: AR
authors.lastname: Turner
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Friedrichsen
authors.forename: Kerry
authors.initials: K
authors.lastname: Deutsch
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kolb
authors.forename: Marta
authors.initials: M
authors.lastname: Janer
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
authors.forename: Charles M
authors.initials: CM
authors.lastname: Ewing
authors.forename: Marta
authors.initials: M
authors.lastname: Gielzak
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Isaacs
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Walsh
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Wiley
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Ho
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Beebe-Dimmer
authors.forename: David P
authors.initials: DP
authors.lastname: Wood
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Cooney
authors.forename: Daniela
authors.initials: D
authors.lastname: Seminara
authors.forename: Tarja
authors.initials: T
authors.lastname: Ikonen
authors.forename: Agnes
authors.initials: A
authors.lastname: Baffoe-Bonnie
authors.forename: Henna
authors.initials: H
authors.lastname: Fredriksson
authors.forename: Mika P
authors.initials: MP
authors.lastname: Matikainen
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.forename: Joan
authors.initials: J
authors.lastname: Bailey-Wilson
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
authors.forename: Christiane
authors.initials: C
authors.lastname: Maier
authors.forename: Kathleen
authors.initials: K
authors.lastname: Herkommer
authors.forename: Josef J
authors.initials: JJ
authors.lastname: Hoegel
authors.forename: Walther
authors.initials: W
authors.lastname: Vogel
authors.forename: Thomas
authors.initials: T
authors.lastname: Paiss
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Monica
authors.initials: M
authors.lastname: Emanuelsson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Stenman
authors.forename: Björn-Anders
authors.initials: BA
authors.lastname: Jonsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Camp
authors.forename: James
authors.initials: J
authors.lastname: Farnham
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.forename: Brian K
authors.initials: BK
authors.lastname: Suarez
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Roehl
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D002874:Chromosome Mapping; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007391:International Cooperation; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics