title: Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease.
abstract: Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p ≤ 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.
authors.affiliation: Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA, craig.teerlink@utah.edu.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Teerlink
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Shannon K
authors.initials: SK
authors.lastname: McDonnell
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.forename: Antje
authors.initials: A
authors.lastname: Rinckleb
authors.forename: Christiane
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authors.lastname: Maier
authors.forename: Walther
authors.initials: W
authors.lastname: Vogel
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cancel-Tassin
authors.forename: Christophe
authors.initials: C
authors.lastname: Egrot
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.forename: Ros
authors.initials: R
authors.lastname: Eeles
authors.forename: Douglas
authors.initials: D
authors.lastname: Easton
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: Michelle
authors.initials: M
authors.lastname: Guy
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Cooney
authors.forename: Anna M
authors.initials: AM
authors.lastname: Ray
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Zuhlke
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.forename: Liesel M
authors.initials: LM
authors.lastname: Fitzgerald
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Wiley
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Isaacs
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Walsh
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Tiina
authors.initials: T
authors.lastname: Wahlfors
authors.forename: Teuvo
authors.initials: T
authors.lastname: Tammela
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Monica
authors.initials: M
authors.lastname: Emanuelsson
authors.forename: John
authors.initials: J
authors.lastname: Carpten
authors.forename: Joan
authors.initials: J
authors.lastname: Bailey-Wilson
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Ingrid
authors.initials: I
authors.lastname: Oakley-Girvan
authors.forename: Chih-Lin
authors.initials: CL
authors.lastname: Hsieh
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Lingyi
authors.initials: L
authors.lastname: Lu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Camp
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors