title: Two independent prostate cancer risk-associated Loci at 11q13.
abstract: Single nucleotide polymorphisms (SNP) at 11q13 were recently implicated in prostate cancer risk by two genome-wide association studies and were consistently replicated in multiple study populations. To explore prostate cancer association in the regions flanking these SNPs, we genotyped 31 tagging SNPs in a approximately 110 kb region at 11q13 in a Swedish case-control study (Cancer of the Prostate in Sweden), including 2,899 cases and 1,722 controls. We found evidence of prostate cancer association for the previously implicated SNPs including rs10896449, which we termed locus 1. In addition, multiple SNPs on the centromeric side of the region, including rs12418451, were also significantly associated with prostate cancer risk (termed locus 2). The two groups of SNPs were separated by a recombination hotspot. We then evaluated these two representative SNPs in an additional approximately 4,000 cases and approximately 3,000 controls from three study populations and confirmed both loci at 11q13. In the combined allelic test of all four populations, P = 4.0 x 10(-11) for rs10896449 at locus 1 and P = 1.2 x 10(-6) for rs12418451 at locus 2, and both remained significant after adjusting for the other locus and study population. The prostate cancer association at these two 11q13 loci was unlikely confounded by prostate-specific antigen (PSA) detection bias because neither SNP was associated with PSA levels in controls. Unlike locus 1, in which no known gene is located, several putative mRNAs are in close proximity to locus 2. Additional confirmation studies at locus 2 and functional studies for both loci are needed to advance our knowledge on the etiology of prostate cancer.
authors.affiliation: Center for Cancer Genomics, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Stevens
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Isaacs
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Shelly
authors.initials: S
authors.lastname: Smith
authors.forename: Kristen
authors.initials: K
authors.lastname: Pruett
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: Jan-Erik
authors.initials: JE
authors.lastname: Johansson
authors.forename: Wennuan
authors.initials: W
authors.lastname: Liu
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Bao-Li
authors.initials: BL
authors.lastname: Chang
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: John
authors.initials: J
authors.lastname: Carpten
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez
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
mesh_terms: D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors