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Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors.

Publication ,  Journal Article
Schildkraut, JM; Iversen, ES; Akushevich, L; Whitaker, R; Bentley, RC; Berchuck, A; Marks, JR
Published in: Cancer Epidemiol Biomarkers Prev
October 2013

BACKGROUND: Six gene expression subtypes of invasive epithelial ovarian cancer were recently defined using microarrays by Tothill and colleagues. The Cancer Genome Atlas (TCGA) project subsequently replicated these subtypes and identified a signature predictive of survival in high-grade serous (HGS) cancers. We previously validated these signatures for use in formalin-fixed paraffin-embedded tissues. The aim of the present study was to determine whether these signatures are associated with specific ovarian cancer risk factors, which would add to the evidence that they reflect the heterogeneous etiology of this disease. METHODS: We modeled signature-specific tumor characteristics and epidemiologic risk factor relationships using multiple regression and multivariate response multiple regression models in 193 patients from a case-control study of epithelial ovarian cancer. RESULTS: We observed associations between the Tothill gene expression subtype signatures and both age at diagnosis (P = 0.0008) and race (P = 0.008). Although most established epidemiologic risk factors were not associated with molecular signatures, there was an association between breast feeding (P = 0.024) and first-degree family history of breast or ovarian cancer (P = 0.034) among the 106 HGS cases. Some of the above associations were validated using gene expression microarray data from the TCGA project. Weak associations were seen with age at menarche and duration of oral contraceptive use and the TCGA survival signature. CONCLUSIONS: These data support the potential for genomic characterization to elucidate the etiologic heterogeneity of epithelial ovarian cancer. IMPACT: This study suggests that molecular signatures may augment the ability to define etiologic subtypes of epithelial ovarian cancer.

Duke Scholars

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

October 2013

Volume

22

Issue

10

Start / End Page

1709 / 1721

Location

United States

Related Subject Headings

  • Young Adult
  • Risk Factors
  • Ovarian Neoplasms
  • North Carolina
  • Neoplasms, Glandular and Epithelial
  • Middle Aged
  • Humans
  • Gene Expression
  • Female
  • Epidemiology
 

Citation

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MLA
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Schildkraut, J. M., Iversen, E. S., Akushevich, L., Whitaker, R., Bentley, R. C., Berchuck, A., & Marks, J. R. (2013). Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors. Cancer Epidemiol Biomarkers Prev, 22(10), 1709–1721. https://doi.org/10.1158/1055-9965.EPI-13-0192
Schildkraut, Joellen M., Edwin S. Iversen, Lucy Akushevich, Regina Whitaker, Rex C. Bentley, Andrew Berchuck, and Jeffrey R. Marks. “Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors.Cancer Epidemiol Biomarkers Prev 22, no. 10 (October 2013): 1709–21. https://doi.org/10.1158/1055-9965.EPI-13-0192.
Schildkraut JM, Iversen ES, Akushevich L, Whitaker R, Bentley RC, Berchuck A, et al. Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors. Cancer Epidemiol Biomarkers Prev. 2013 Oct;22(10):1709–21.
Schildkraut, Joellen M., et al. “Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors.Cancer Epidemiol Biomarkers Prev, vol. 22, no. 10, Oct. 2013, pp. 1709–21. Pubmed, doi:10.1158/1055-9965.EPI-13-0192.
Schildkraut JM, Iversen ES, Akushevich L, Whitaker R, Bentley RC, Berchuck A, Marks JR. Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors. Cancer Epidemiol Biomarkers Prev. 2013 Oct;22(10):1709–1721.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

October 2013

Volume

22

Issue

10

Start / End Page

1709 / 1721

Location

United States

Related Subject Headings

  • Young Adult
  • Risk Factors
  • Ovarian Neoplasms
  • North Carolina
  • Neoplasms, Glandular and Epithelial
  • Middle Aged
  • Humans
  • Gene Expression
  • Female
  • Epidemiology