title: Multiple loci identified in a genome-wide association study of prostate cancer.
abstract: We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 x 10(-13) and P < 2.14 x 10(-6)). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 x 10(-5)), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Jacobs
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Nick
authors.initials: N
authors.lastname: Orr
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Robert
authors.initials: R
authors.lastname: Welch
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Andrew
authors.initials: A
authors.lastname: Crenshaw
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cancel-Tassin
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Staats
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Jesus
authors.initials: J
authors.lastname: Gonzalez-Bosquet
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.forename: Xiang
authors.initials: X
authors.lastname: Deng
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Eugenia E
authors.initials: EE
authors.lastname: Calle
authors.forename: Heather Spencer
authors.initials: HS
authors.lastname: Feigelson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Stephanie
authors.initials: S
authors.lastname: Weinstein
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.forename: Antoine
authors.initials: A
authors.lastname: Valeri
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Andriole
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
authors.forename: Margaret
authors.initials: M
authors.lastname: Tucker
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Gerhard
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: Robert
authors.initials: R
authors.lastname: Hoover
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
mesh_terms: D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D019410:Interleukin-16 / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D010750:Phosphoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D040641:Quantitative Trait Loci; D044465:White People / Q000235:genetics
chemical_list: D015820:Cadherins; C099972:H-cadherin; D019410:Interleukin-16; D010750:Phosphoproteins; C415882:copine III