Abstract
BackgroundThe 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.MethodsWe 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.ResultsThe minor allele for one synonymous SNP in NFKBIA, rs1957106, was associated with decreased risk (p = 0.03).ConclusionConsidering 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.
Highlights
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
DNA samples were transferred to Mayo Clinic and, because of the relatively low quantities of DNA, they were whole-genome amplified (WGA) with the REPLI-G protocol (Qiagen Inc, Valencia CA) which we have shown to yield highly reproducible results with these samples [28]
We identified tagSNPs within five kb of NFKBIA and NFKBIB using the algorithm of ldSelect [29] to bin pairwise-correlated single nucleotide polymorphisms (SNPs) at r2 ≥ 0.80 with minor allele frequency (MAF) ≥ 0.05 among publiclyavailable European-American data from the National Heart, Lung, and Blood Institute's Program for Genomic Applications SeattleSNPs gene-resequencing effort [30]
Summary
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. During ovulation the ovarian epithelial surface is damaged, requiring a repair process involving the recruitment of leukocytes and inflammatory cytokines, release of nitrous oxide, DNA repair, and tissue restructuring [6,7,8,9] Over time, this continuous repair of the ovarian epithelial tissue increases the likelihood of errors during replication, potentially leading to carcinogenesis. Ovarian tumors acquire aberrant NF-κB functions allowing them to circumvent apoptotic pathways, tumor necrosis factor alpha(TNFα)-induced apoptosis, and afford protection against environmental insults such as anti-tumor immune effectors or chemotherapy [16,17,18,19]
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