Genomics of the NF-?B signaling pathway: hypothesized role in ovarian cancer.

ABSTRACT: We sought to review evidence linking nuclear factor-kappa B (NF-?B) to ovarian cancer and to identify genetic variants involved in NF-?B signaling.PubMed was reviewed to inform on ovarian cancer biology and NF-?B signaling and to identify key genes. Public linkage disequilibrium (LD) data were analyzed to identify informative inherited variants (tagSNPs) using ldSelect.We identified 319 key NF-?B genes including five NF-?B 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-?B SNPs of interest.Compelling evidence suggests that NF-?B 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.

SUBMITTER: White KL 

PROVIDER: S-EPMC3119514 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature