title: Fine-mapping CASP8 risk variants in breast cancer.
abstract: BACKGROUND
  Multiple genome-wide and candidate gene association studies have been conducted in search of common risk variants for breast cancer. Recent large meta analyses, consolidating evidence from these studies, have been consistent in highlighting the caspase-8 (CASP8) gene as important in this regard. To define a risk haplotype and map the CASP8 gene region with respect to underlying susceptibility variant/s, we screened four genes in the CASP8 region on 2q33-q34 for breast cancer risk.
  
  
  METHODS
  Two independent data sets from the United Kingdom and the United States, including 3,888 breast cancer cases and controls, were genotyped for 45 tagging single nucleotide polymorphisms (tSNP) in the expanded CASP8 region. SNP and haplotype association tests were carried out using Monte Carlo-based methods.
  
  
  RESULTS
  We identified a three-SNP haplotype across rs3834129, rs6723097, and rs3817578 that was significantly associated with breast cancer (P < 5 × 10(-6)), with a dominant risk ratio and 95% CI of 1.28 (1.21-1.35) and frequency of 0.29 in controls. Evidence for this risk haplotype was extremely consistent across the two study sites and also consistent with previous data.
  
  
  CONCLUSIONS
  This three-SNP risk haplotype represents the best characterization so far of the chromosome upon which the susceptibility variant resides.
  
  
  CONCLUSIONS
  Characterization of the risk haplotype provides a strong foundation for resequencing efforts to identify the underlying risk variant, which may prove useful for individual-level risk prediction, and provide novel insights into breast carcinogenesis.
authors: Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors: Nicola J
authors: NJ
authors: Camp
authors: Marina
authors: M
authors: Parry
authors: Stacey
authors: S
authors: Knight
authors: Ryan
authors: R
authors: Abo
authors: Graeme
authors: G
authors: Elliott
authors: Sushilaben H
authors: SH
authors: Rigas
authors: Sabapathy P
authors: SP
authors: Balasubramanian
authors: Malcolm W R
authors: MW
authors: Reed
authors: Helen
authors: H
authors: McBurney
authors: Ayse
authors: A
authors: Latif
authors: William G
authors: WG
authors: Newman
authors: Lisa A
authors: LA
authors: Cannon-Albright
authors: D Gareth
authors: DG
authors: Evans
authors: Angela
authors: A
authors: Cox
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D053181:Caspase 8