title: Sequence variants at 22q13 are associated with prostate cancer risk.
abstract: To search for genetic variants that are associated with prostate cancer risk in the genome, we combined the data from our genome-wide association study (GWAS) in a population-based case-control study in Sweden with publicly available GWAS data from the Cancer Genetic Markers of Susceptibility (CGEMS) study. We limited the cases to those with aggressive disease in an attempt to identify risk variants that are associated with this most clinically relevant form of the disease. Among the most likely candidate single nucleotide polymorphisms (SNP) identified from the two GWAS, we sequentially confirmed one SNP at 22q13 in two independent study populations: the remaining subjects in Cancer of the Prostate in Sweden and a hospital-based case-control study at Johns Hopkins Hospital. Association of aggressive prostate cancer with the SNP at 22q13 was also observed in the publicly available data of four additional study populations from the second stage of the CGEMS study. In all seven study populations examined, the frequency of allele "C" of rs9623117 at 22q13 was consistently higher in aggressive cases than in controls. The combined allelic test was highly significant, with P = 5.0 x 10(-7). The odds ratio (OR) of allele C for aggressive prostate cancer was estimated to be 1.18 [95% confidence interval (95% CI), 1.11-1.26]. However, the SNP was also associated with nonaggressive prostate cancer, with an estimated OR of 1.11 (95% CI, 1.04-1.19; P = 0.004). The risk-associated variants are located within the genomic region of TNRC6B, a gene involved in miRNA-mediated mRNA degradation. Additional studies are warranted to further confirm the association.
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Siqun Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Isaacs
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Wiley
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu
authors.forename: Aubrey R
authors.initials: AR
authors.lastname: Turner
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Wennuan
authors.initials: W
authors.lastname: Liu
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: John
authors.initials: J
authors.lastname: Carpten
authors.forename: William
authors.initials: W
authors.lastname: Isaacs
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Bao-Li
authors.initials: BL
authors.lastname: Chang
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002892:Chromosomes, Human, Pair 22; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*