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Open Access Research article

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

Kristin L White1, Robert A Vierkant1, Catherine M Phelan2, Brooke L Fridley1, Stephanie Anderson1, Keith L Knutson1, Joellen M Schildkraut3, Julie M Cunningham1, Linda E Kelemen4, V Shane Pankratz1, David N Rider1, Mark Liebow1, Lynn C Hartmann1, Thomas A Sellers2 and Ellen L Goode1*

Author Affiliations

1 Mayo Clinic College of Medicine, Rochester, MN, USA

2 H. Lee Moffitt Cancer Research Institute, Tampa, FL, USA

3 Duke University, Durham, NC, USA

4 Alberta Cancer Board, Calgary, AB, USA

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BMC Cancer 2009, 9:170  doi:10.1186/1471-2407-9-170

Published: 6 June 2009

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.