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Gene set analysis of survival following ovarian cancer implicates macrolide binding and intracellular signaling genes.

Publication ,  Journal Article
Fridley, BL; Jenkins, GD; Tsai, Y-Y; Song, H; Bolton, KL; Fenstermacher, D; Tyrer, J; Ramus, SJ; Cunningham, JM; Vierkant, RA; Chen, Z ...
Published in: Cancer Epidemiol Biomarkers Prev
March 2012

BACKGROUND: Genome-wide association studies (GWAS) for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy, have identified novel susceptibility loci. GWAS for survival after EOC have had more limited success. The association of each single-nucleotide polymorphism (SNP) individually may not be well suited to detect small effects of multiple SNPs, such as those operating within the same biologic pathway. Gene set analysis (GSA) overcomes this limitation by assessing overall evidence for association of a phenotype with all measured variation in a set of genes. METHODS: To determine gene sets associated with EOC overall survival, we conducted GSA using data from two large GWAS (N cases = 2,813, N deaths = 1,116), with a novel Principal Component-Gamma GSA method. Analysis was completed for all cases and then separately for high-grade serous histologic subtype. RESULTS: Analysis of the high-grade serous subjects resulted in 43 gene sets with P < 0.005 (1.7%); of these, 21 gene sets had P < 0.10 in both GWAS, including intracellular signaling pathway (P = 7.3 × 10(-5)) and macrolide binding (P = 6.2 × 10(-4)) gene sets. The top gene sets in analysis of all cases were meiotic mismatch repair (P = 6.3 × 10(-4)) and macrolide binding (P = 1.0 × 10(-3)). Of 18 gene sets with P < 0.005 (0.7%), eight had P < 0.10 in both GWAS. CONCLUSION: This research detected novel gene sets associated with EOC survival. IMPACT: Novel gene sets associated with EOC survival might lead to new insights and avenues for development of novel therapies for EOC and pharmacogenomic studies.

Duke Scholars

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

March 2012

Volume

21

Issue

3

Start / End Page

529 / 536

Location

United States

Related Subject Headings

  • Survival Rate
  • Signal Transduction
  • Risk Factors
  • Prognosis
  • Principal Component Analysis
  • Ovarian Neoplasms
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Invasiveness
  • Neoplasm Grading
  • Middle Aged
 

Citation

APA
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MLA
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Fridley, B. L., Jenkins, G. D., Tsai, Y.-Y., Song, H., Bolton, K. L., Fenstermacher, D., … Goode, E. L. (2012). Gene set analysis of survival following ovarian cancer implicates macrolide binding and intracellular signaling genes. Cancer Epidemiol Biomarkers Prev, 21(3), 529–536. https://doi.org/10.1158/1055-9965.EPI-11-0741
Fridley, Brooke L., Gregory D. Jenkins, Ya-Yu Tsai, Honglin Song, Kelly L. Bolton, David Fenstermacher, Jonathan Tyrer, et al. “Gene set analysis of survival following ovarian cancer implicates macrolide binding and intracellular signaling genes.Cancer Epidemiol Biomarkers Prev 21, no. 3 (March 2012): 529–36. https://doi.org/10.1158/1055-9965.EPI-11-0741.
Fridley BL, Jenkins GD, Tsai Y-Y, Song H, Bolton KL, Fenstermacher D, et al. Gene set analysis of survival following ovarian cancer implicates macrolide binding and intracellular signaling genes. Cancer Epidemiol Biomarkers Prev. 2012 Mar;21(3):529–36.
Fridley, Brooke L., et al. “Gene set analysis of survival following ovarian cancer implicates macrolide binding and intracellular signaling genes.Cancer Epidemiol Biomarkers Prev, vol. 21, no. 3, Mar. 2012, pp. 529–36. Pubmed, doi:10.1158/1055-9965.EPI-11-0741.
Fridley BL, Jenkins GD, Tsai Y-Y, Song H, Bolton KL, Fenstermacher D, Tyrer J, Ramus SJ, Cunningham JM, Vierkant RA, Chen Z, Chen YA, Iversen E, Menon U, Gentry-Maharaj A, Schildkraut J, Sutphen R, Gayther SA, Hartmann LC, Pharoah PDP, Sellers TA, Goode EL. Gene set analysis of survival following ovarian cancer implicates macrolide binding and intracellular signaling genes. Cancer Epidemiol Biomarkers Prev. 2012 Mar;21(3):529–536.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

March 2012

Volume

21

Issue

3

Start / End Page

529 / 536

Location

United States

Related Subject Headings

  • Survival Rate
  • Signal Transduction
  • Risk Factors
  • Prognosis
  • Principal Component Analysis
  • Ovarian Neoplasms
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Invasiveness
  • Neoplasm Grading
  • Middle Aged