IκBKβ and NFκB1, NSAID use and risk of colorectal cancer in the colon cancer family registry

Brenna L. Seufert, Elizabeth M. Poole, John Whitton, Liren Xiao, Karen W. Makar, Peter T. Campbell, Richard J. Kulmacz, John A. Baron, Polly A. Newcomb, Martha L. Slattery, John D. Potter, Cornelia M. Ulrich

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


The NFκB-signaling pathway regulates cell proliferation and inflammation. Activation of the pathway is implicated in the etiology of colorectal cancer (CRC). NSAIDs may reduce CRC risk partially through a nuclear factor-kappa B (NFκB)-dependent pathway. In this study, we investigated associations between 34 NFκB1 and 8 IκBKβ tagSNPs and CRC risk and examined interactions with non-steroidal anti-inflammatory drug (NSAID) use. Using conditional logistic regression, we investigated these associations among 1584 incident CRC cases and 2516 sibling controls from the Colon Cancer Family Registry. Three IκBKβ SNPs were associated with a statistically significant lower colorectal or colon cancer risk: rs9694958 (A>G intron 5) (colorectal: ORhzv = 0.26(0.07-0.99), Ptrend = 0.048, Padj = 0.25), rs10958713 (A>C intron 19) (colon: ORhzv = 0.62(0.42-0.92), Ptrend = 0.005, Padj = 0.03) and rs5029748 (C>A intron 2) (colon: ORhet = 0.72(0.56-0.91), Ptrend = 0.01, Padj = 0.08). We replicated trends associated with NFκB1 and IκBKβ variants identified in a previous study (rs4648110 (T>A intron 22), rs13117745 (G>A intron 5) and rs3747811 (T>A intron 1)). IκBKβ's rs6474387 (C>T intron 20) and rs11986055 (A>C intron 2) showed substantially lower colon cancer risk among current NSAID users (Pinteraction = 0.01 and Pinteraction = 0.045, respectively), whereas NFκB1's rs230490 (G>A 5? (outside UTR)) and rs997476 (C>A 3? (outside UTR)) showed higher CRC risk among current NSAID users (Pinteraction = 0.01 and Pinteraction = 0.03, respectively). These findings suggest that variants in NFκB1 and IκBKβ are associated with CRC risk and NSAIDs may function partially through an NFκB-dependent pathway. The SNPs identified here should be considered for future functional studies and may be useful in designing a pharmacogenetic approach to preventive NSAID use.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
Issue number1
StatePublished - Jan 2013
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research


Dive into the research topics of 'IκBKβ and NFκB1, NSAID use and risk of colorectal cancer in the colon cancer family registry'. Together they form a unique fingerprint.

Cite this