title: Fine mapping of 11q13.5 identifies regions associated with prostate cancer and prostate cancer death.
abstract: BACKGROUND
  Chromosomal region 11q13-14 associates with prostate cancer (PrCa). Previously, we identified a rare intronic mutation on EMSY (11q13.5) that increases the risk of aggressive PrCa and associates with familial PrCa. Here, we further study the genetic structure and variants of the PrCa susceptibility region 11q13.5.
  
  
  METHODS
  This study included 2716 unselected hospital-based PrCa cases, 1318 cases of a screening trial and 908 controls of Finnish origin. We imputed single nucleotide polymorphisms (SNPs) and structural variants from the 1000 Genomes Project and validated the associations of the variants in two PrCa patient sets by genotyping. Genetic structure was studied with haplotype analysis.
  
  
  RESULTS
  Two independent regions at 11q13.5 were associated with PrCa risk. The most significant association was at EMSY (rs10899221, odds ratio (OR) 1.29-1.40, P=3.5 × 10(-4)-0.002) near the previously identified mutation. Correlated intronic SNPs rs10899221 and rs72944758 formed with other EMSY variants common and rare haplotypes that were associated with increased risk (P=4.0 × 10(-4)) and decreased risk (P=0.01) of PrCa, respectively. The other associated region was intergenic. Among the six validated variants, rs12277366 was significant in both patient sets (OR 1.15-1.17, P=0.01). Haplotypes associated with an increased risk (P=0.02) and a decreased risk (P=0.02) were identified. In addition, the intergenic region was strongly associated with PrCa death, with the most significant association at rs12277366 (OR=0.72, P=4.8 × 10(-5)).
  
  
  CONCLUSIONS
  These findings indicate that 11q13.5 contributes to PrCa predisposition with complex genetic structure and is associated with PrCa death.
authors.affiliation: Institute of Biomedical Technology/BioMediTech and Prostate Cancer Research Center, University of Tampere and Fimlab Laboratories, Biokatu 8, FI-33014 Tampere, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Nurminen
authors.forename: Rainer
authors.initials: R
authors.lastname: Lehtonen
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.forename: Tiina
authors.initials: T
authors.lastname: Wahlfors
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality; D012307:Risk Factors
keywords: Death; EMSY; Genetic association study; Prostate cancer; Single nucleotide polymorphism