IκBKβ and NFκB1, NSAID Use and Risk of Colorectal Cancer in the Colon Cancer Family Registry
A partir des données d'un registre américain portant sur 1 584 patients atteints d'un cancer colorectal et sur 2 516 témoins frères et soeurs, cette étude évalue l'association entre des polymorphismes à simple nucléotide des gènes IκBKβ et NFκB1, l'utilisation d'anti-inflammatoires non stéroïdiens et le risque de développer la maladie
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 an NFκB-dependent pathway. Here, we investigated associations between 34 NFκB1 and eight IκBKβ tagSNPs and CRC risk and examined interactions with NSAID use. Using conditional logistic regression, we investigated these associations among 1,584 incident CRC cases and 2,516 sibling controls from the Colorectal Cancer Family Registry. Three IκBKβ SNPs were associated with a statistically significant lower colorectal or colon cancer risk: rs9694958 (colorectal: ORhzv=0.26(0.07-0.99), p-trend=0.048, padj=0.25), rs10958713 (colon: ORhzv=0.62(0.42-0.92), p-trend=0.005, padj=0.03) and rs5029748 (colon: ORhet=0.72(0.56-0.91), p-trend=0.01, padj=0.08). We replicated trends associated with NFκB1 and IκBKβ variants identified in a previous study (rs4648110, rs13117745, rs3747811). IκBKβ’s rs6474387 and rs11986055 showed substantially lower colon cancer risk among current NSAID users (pinteraction=0.01 and pinteraction=0.045), whereas NFκB1’s rs230490 and rs997476 showed higher CRC risk among current NSAID users (pinteraction=0.01 and pinteraction=0.03). 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.
http://carcin.oxfordjournals.org/content/early/2012/09/21/carcin.bgs296.abstract