The effects of common genetic variants in oncogenes on ovarian cancer survival

L. Quaye; S.A. Gayther; S.J. Ramus; R.A. Di Cioccio; V. McGuire; C. Hogdall; J. Blaakr; D.F. Easton; B.A. Ponder; I. Jacobs; S.K. Kjaer; A.S. Whittemore; C.L. Pearce; P.D. Pharoah; H. Song; Estrid Vilma Solyom Høgdall

The effects of common genetic variants in oncogenes on ovarian cancer survival

L. Quaye, S.A. Gayther, S.J. Ramus, R.A. Di Cioccio, V. McGuire, C. Hogdall, J. Blaakr, D.F. Easton, B.A. Ponder, I. Jacobs, S.K. Kjaer, A.S. Whittemore, C.L. Pearce, P.D. Pharoah, H. Song, Estrid Vilma Solyom Høgdall

25 Citationer (Scopus)

Abstract

PURPOSE: 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. EXPERIMENTAL DESIGN: 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). CONCLUSION: Common genetic variants in the BRAF and KRAS oncogenes may be important in the prediction of survival in patients with invasive epithelial ovarian cancer
Udgivelsesdato: 2008/9/15

Originalsprog	Dansk
Tidsskrift	Clinical Cancer Research
Vol/bind	14
Udgave nummer	18
Sider (fra-til)	5833-5839
Antal sider	6
ISSN	1078-0432
Status	Udgivet - 2008

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@article{12fbb5408d6611de8bc9000ea68e967b,

title = "The effects of common genetic variants in oncogenes on ovarian cancer survival",

abstract = "PURPOSE: 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. EXPERIMENTAL DESIGN: 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). CONCLUSION: Common genetic variants in the BRAF and KRAS oncogenes may be important in the prediction of survival in patients with invasive epithelial ovarian cancer Udgivelsesdato: 2008/9/15",

author = "L. Quaye and S.A. Gayther and S.J. Ramus and Cioccio, {R.A. Di} and V. McGuire and C. Hogdall and J. Blaakr and D.F. Easton and B.A. Ponder and I. Jacobs and S.K. Kjaer and A.S. Whittemore and C.L. Pearce and P.D. Pharoah and H. Song and H{\o}gdall, {Estrid Vilma Solyom}",

note = "IS - 1078-0432 (Print)LA - engPT - Journal ArticlePT - Research Support, N.I.H., ExtramuralPT - Research Support, Non-U.S. Gov'tRN - 0 (KRAS protein, human)RN - 0 (Proto-Oncogene Proteins)RN - EC 2.7.1.37 (BRAF protein, human)RN - EC 2.7.1.37 (Proto-Oncogene Proteins B-raf)RN - EC 3.6.5.2 (ras Proteins)SB - IM",

year = "2008",

language = "Dansk",

volume = "14",

pages = "5833--5839",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research (A A C R)",

number = "18",

}

TY - JOUR

T1 - The effects of common genetic variants in oncogenes on ovarian cancer survival

AU - Quaye, L.

AU - Gayther, S.A.

AU - Ramus, S.J.

AU - Cioccio, R.A. Di

AU - McGuire, V.

AU - Hogdall, C.

AU - Blaakr, J.

AU - Easton, D.F.

AU - Ponder, B.A.

AU - Jacobs, I.

AU - Kjaer, S.K.

AU - Whittemore, A.S.

AU - Pearce, C.L.

AU - Pharoah, P.D.

AU - Song, H.

AU - Høgdall, Estrid Vilma Solyom

N1 - IS - 1078-0432 (Print)LA - engPT - Journal ArticlePT - Research Support, N.I.H., ExtramuralPT - Research Support, Non-U.S. Gov'tRN - 0 (KRAS protein, human)RN - 0 (Proto-Oncogene Proteins)RN - EC 2.7.1.37 (BRAF protein, human)RN - EC 2.7.1.37 (Proto-Oncogene Proteins B-raf)RN - EC 3.6.5.2 (ras Proteins)SB - IM

PY - 2008

Y1 - 2008

N2 - PURPOSE: 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. EXPERIMENTAL DESIGN: 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). CONCLUSION: Common genetic variants in the BRAF and KRAS oncogenes may be important in the prediction of survival in patients with invasive epithelial ovarian cancer Udgivelsesdato: 2008/9/15

AB - PURPOSE: 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. EXPERIMENTAL DESIGN: 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). CONCLUSION: Common genetic variants in the BRAF and KRAS oncogenes may be important in the prediction of survival in patients with invasive epithelial ovarian cancer Udgivelsesdato: 2008/9/15

M3 - Tidsskriftartikel

SN - 1078-0432

VL - 14

SP - 5833

EP - 5839

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 18

ER -