title: Inherited determinants of ovarian cancer survival.
abstract: OBJECTIVE
  Due to variation of outcome among cases, we sought to examine whether overall survival in ovarian cancer was associated with common inherited variants in 227 candidate genes from ovarian cancer-related pathways including angiogenesis, inflammation, detoxification, glycosylation, one-carbon transfer, apoptosis, cell cycle regulation, and cellular senescence.
  
  
  METHODS
  Blood samples were obtained from 325 women with invasive epithelial ovarian cancer diagnosed at the Mayo Clinic from 1999 to 2006. During a median follow-up of 3.8 years (range, 0.1-8.6 years), 157 deaths were observed. Germline DNA was analyzed at 1,416 single nucleotide polymorphisms (SNP). For all patients, and for 203 with serous subtype, we assessed the overall significance of each gene and pathway, and estimated risk of death via hazard ratios (HR) and 95% confidence intervals (CI), adjusting for known prognostic factors.
  
  
  RESULTS
  Variation within angiogenesis was most strongly associated with survival time overall (P = 0.03) and among patients with serous cancer (P = 0.05), particularly for EIF2B5 rs4912474 (all patients HR, 0.69; 95% CI, 0.54-0.89; P = 0.004), VEGFC rs17697305 (serous subtype HR, 2.29; 95% CI, 1.34-3.92; P = 0.003), and four SNPs in VHL. Variation within the inflammation pathway was borderline significant (all patients, P = 0.09), and SNPs in CCR3, IL1B, IL18, CCL2, and ALOX5 which correlated with survival time are worthy of follow-up.
  
  
  CONCLUSIONS
  An extensive multiple-pathway assessment found evidence that inherited differences may play a role in outcome of ovarian cancer patients, particularly in genes within the angiogenesis and inflammation pathways. Our work supports efforts to target such mediators for therapeutic gain.
authors.affiliation: Mayo Clinic College of Medicine, Rochester, Minnesota, USA. egoode@mayo.edu
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phelan
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Kalli
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Armasu
authors.forename: Kristin L
authors.initials: KL
authors.lastname: White
authors.forename: Gary L
authors.initials: GL
authors.lastname: Keeney
authors.forename: William A
authors.initials: WA
authors.lastname: Cliby
authors.forename: David N
authors.initials: DN
authors.lastname: Rider
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.forename: Monica B
authors.initials: MB
authors.lastname: Jones
authors.forename: Prema P
authors.initials: PP
authors.lastname: Peethambaram
authors.forename: Johnathan M
authors.initials: JM
authors.lastname: Lancaster
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Hartmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality*; D020641:Polymorphism, Single Nucleotide