Genomics of the NF-κB signaling pathway: Hypothesized role in ovarian cancer

Kristin L. White, David N. Rider, Kimberly R. Kalli, Keith L. Knutson, Gail P. Jarvik, Ellen L. Goode

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Objective: We sought to review evidence linking nuclear factor-kappa B (NF-κB) to ovarian cancer and to identify genetic variants involved in NF-κB signaling. Methods: PubMed was reviewed to inform on ovarian cancer biology and NF-κB signaling and to identify key genes. Public linkage disequilibrium (LD) data were analyzed to identify informative inherited variants (tagSNPs) using ldSelect. Results: We identified 319 key NF-κB genes including five NF-κB subunits, 167 activating genes, and 55 inhibiting genes. We found that the 1000 Genomes Project was the most informative LD source for most genes (92.8%), and we identified 13,027 LD bins (r 2 ≥ 0.9, minor allele frequency ≥0.05) and 1,018 putative-functional variants worthy of investigation. We also report that reliance on a commonly used genome-wide SNP array and genotype imputation with HapMap Phase II data provides data on only 74% of the common inherited NF-κB SNPs of interest. Conclusions: Compelling evidence suggests that NF-κB plays a critical role in ovarian cancer, yet inherited variation in these genes has not been thoroughly assessed in relation to disease risk or outcome. We present a collection of variants in key genes and suggest creation of a custom genotyping array as an optimal approach.

Original languageEnglish (US)
Pages (from-to)785-801
Number of pages17
JournalCancer Causes and Control
Volume22
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • Association studies
  • Etiology
  • Genetic variation
  • NF-kappaB
  • Single nucleotide polymorphisms
  • tagSNPs

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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