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Polymorphisms in NF-κB Inhibitors and Risk of Epithelial Ovarian Cancer

Author(s): White Kristin | Vierkant Robert | Phelan Catherine | Fridley Brooke | Anderson Stephanie | Knutson Keith | Schildkraut Joellen | Cunningham Julie | Kelemen Linda | Pankratz V Shane | Rider David | Liebow Mark | Hartmann Lynn | Sellers Thomas | Goode Ellen

Journal: BMC Cancer
ISSN 1471-2407

Volume: 9;
Issue: 1;
Start page: 170;
Date: 2009;
Original page

Abstract Background The nuclear factor-κB (NF-κB) family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of κB (IκB) prevent NF-κB activation by sequestering NF-κB proteins in the cytoplasm until IκB proteins are phosphorylated and degraded. Methods We used a case-control study to evaluate the association between single nucleotide polymorphisms (SNPs) in NFKBIA and NFKBIB (the genes encoding IκBα and IκBβ, respectively) and risk of epithelial ovarian cancer. We queried 19 tagSNPs and putative-functional SNPs among 930 epithelial ovarian cancer cases and 1,037 controls from two studies. Results The minor allele for one synonymous SNP in NFKBIA, rs1957106, was associated with decreased risk (p = 0.03). Conclusion Considering the number of single-SNP tests performed and null gene-level results, we conclude that NFKBIA and NFKBIB are not likely to harbor ovarian cancer risk alleles. Due to its biological significance in ovarian cancer, additional genes encoding NF-κB subunits, activating and inhibiting molecules, and signaling molecules warrant interrogation.
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