The effects of common genetic variants in oncogenes on ovarian cancer survival.
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.
Quaye
Lydia
L
Gynaecological Cancer Research Laboratory, UCL EGA Institute for Women's Health, University College London, London, United Kingdom.
Gayther
Simon A
SA
Ramus
Susan J
SJ
Di Cioccio
Richard A
RA
McGuire
Valerie
V
Hogdall
Estrid
E
Hogdall
Claus
C
Blaakr
Jan
J
Easton
Douglas F
DF
Ponder
Bruce A J
BA
Jacobs
Ian
I
Kjaer
Susanne Kruger
SK
Whittemore
Alice S
AS
Pearce
Celeste Leigh
CL
Pharoah
Paul D P
PD
Song
Honglin
H
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
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