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

KL White, DN Rider, KR Kalli, KL Knutson… - Cancer Causes & …, 2011 - Springer
KL White, DN Rider, KR Kalli, KL Knutson, GP Jarvik, EL Goode
Cancer Causes & Control, 2011Springer
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 …
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.
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