I?BK? and NF?B1, NSAID use and risk of colorectal cancer in the Colon Cancer Family Registry.
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ABSTRACT: The NF?B-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 (NF?B)-dependent pathway. In this study, we investigated associations between 34 NF?B1 and 8 I?BK? 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 I?BK? SNPs were associated with a statistically significant lower colorectal or colon cancer risk: rs9694958 (A>G intron 5) (colorectal: OR(hzv) = 0.26(0.07-0.99), P(trend) = 0.048, P(adj) = 0.25), rs10958713 (A>C intron 19) (colon: OR(hzv) = 0.62(0.42-0.92), P(trend) = 0.005, P(adj) = 0.03) and rs5029748 (C>A intron 2) (colon: OR(het) = 0.72(0.56-0.91), P(trend) = 0.01, P(adj) = 0.08). We replicated trends associated with NF?B1 and I?BK? variants identified in a previous study (rs4648110 (T>A intron 22), rs13117745 (G>A intron 5) and rs3747811 (T>A intron 1)). I?BK?'s rs6474387 (C>T intron 20) and rs11986055 (A>C intron 2) showed substantially lower colon cancer risk among current NSAID users (P(interaction) = 0.01 and P(interaction) = 0.045, respectively), whereas NF?B1's rs230490 (G>A 5' (outside UTR)) and rs997476 (C>A 3' (outside UTR)) showed higher CRC risk among current NSAID users (P(interaction) = 0.01 and P(interaction) = 0.03, respectively). These findings suggest that variants in NF?B1 and I?BK? are associated with CRC risk and NSAIDs may function partially through an NF?B-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.
SUBMITTER: Seufert BL
PROVIDER: S-EPMC3534188 | biostudies-literature | 2013 Jan
REPOSITORIES: biostudies-literature
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