Journal
CANCER CAUSES & CONTROL
Volume 22, Issue 5, Pages 785-801Publisher
SPRINGER
DOI: 10.1007/s10552-011-9745-4
Keywords
Association studies; Genetic variation; NF-kappaB; Etiology; tagSNPs; Single nucleotide polymorphisms
Funding
- NCI [R01-CA122443]
- Mayo Clinic SPORE in Ovarian Cancer [P50 CA136393]
- Mayo Foundation
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Objective We sought to review evidence linking nuclear factor-kappa B (NF-kappa B) to ovarian cancer and to identify genetic variants involved in NF-kappa B signaling. Methods PubMed was reviewed to inform on ovarian cancer biology and NF-kappa B 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-kappa B genes including five NF-kappa 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) a parts per thousand yen 0.9, minor allele frequency a parts per thousand yen0.05) 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-kappa B SNPs of interest. Conclusions Compelling evidence suggests that NF-kappa 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.
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