Polymorphisms in NF-kappaB inhibitors and risk of epithelial ovarian cancer.
BACKGROUND
The nuclear factor-kappaB (NF-kappaB) 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 kappaB (IkappaB) prevent NF-kappaB activation by sequestering NF-kappaB proteins in the cytoplasm until IkappaB 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 IkappaBalpha and IkappaBbeta, 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).


CONCLUSIONS
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-kappaB subunits, activating and inhibiting molecules, and signaling molecules warrant interrogation.
White
Kristin L
KL
Mayo Clinic College of Medicine, Rochester, MN, USA. white.kristin@mayo.edu
Vierkant
Robert A
RA
Phelan
Catherine M
CM
Fridley
Brooke L
BL
Anderson
Stephanie
S
Knutson
Keith L
KL
Schildkraut
Joellen M
JM
Cunningham
Julie M
JM
Kelemen
Linda E
LE
Pankratz
V Shane
VS
Rider
David N
DN
Liebow
Mark
M
Hartmann
Lynn C
LC
Sellers
Thomas A
TA
Goode
Ellen L
EL
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha