title: The effects of common genetic variants in oncogenes on ovarian cancer survival.
abstract: OBJECTIVE
  The 5-year survival rate for invasive epithelial ovarian cancer is <35%. It has been suggested that common, germline genetic variation may influence survival after cancer diagnoses, which might enable the prediction of response to treatment and survival in the clinical setting. The aim of this study was to evaluate associations between common germline genetic variants in the oncogenes BRAF, ERBB2, KRAS, NMI, and PIK3CA, and survival after a diagnosis of epithelial ovarian cancer.
  
  
  METHODS
  We evaluated the association between 34 tagging single nucleotide polymorphisms and survival in 1,480 cases of invasive epithelial ovarian cancer cases from three different studies. Cox regression analysis, stratified by study, was used to estimate per rare allele hazard ratios (HR).
  
  
  RESULTS
  The minor allele rs6944385 in BRAF was significantly associated with poor survival [HR, 1.19; 95% confidence intervals (95% CI), 1.02-1.39; P = 0.024]. The association remained after adjusting for prognostic factors (adjusted HR, 1.20; 95 CI, 1.03-1.40; P = 0.018). A haplotype of BRAF was also associated with poor survival (HR, 1.24; 95% CI, 1.02-1.51; P = 0.029) and was more significant after adjustment (HR, 1.44; 95% CI, 1.15-1.81; P = 0.001). We also found evidence of an association between a KRAS haplotype and poor survival in serous subtype (HR, 1.69; 95% CI, 1.21-2.38; P = 0.002), but this was no longer significant after adjustment. Finally, when analyses were restricted to the serous histologic subtype, the rare allele rs10842513 in KRAS, was associated with poor survival (HR, 1.40; 95% CI, 1.10-1.78; P = 0.007).
  
  
  CONCLUSIONS
  Common genetic variants in the BRAF and KRAS oncogenes may be important in the prediction of survival in patients with invasive epithelial ovarian cancer.
authors.affiliation: Gynaecological Cancer Research Laboratory, UCL EGA Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Lydia
authors.initials: L
authors.lastname: Quaye
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Richard A
authors.initials: RA
authors.lastname: Di Cioccio
authors.forename: Valerie
authors.initials: V
authors.lastname: McGuire
authors.forename: Estrid
authors.initials: E
authors.lastname: Hogdall
authors.forename: Claus
authors.initials: C
authors.lastname: Hogdall
authors.forename: Jan
authors.initials: J
authors.lastname: Blaakr
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Bruce A J
authors.initials: BA
authors.lastname: Ponder
authors.forename: Ian
authors.initials: I
authors.lastname: Jacobs
authors.forename: Susanne Kruger
authors.initials: SK
authors.lastname: Kjaer
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Celeste Leigh
authors.initials: CL
authors.lastname: Pearce
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
mesh_terms: D005260:Female; D005838:Genotype; D006801:Humans; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins