Journal
CARCINOGENESIS
Volume 34, Issue 1, Pages 79-85Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgs296
Keywords
-
Categories
Funding
- National Cancer Institute [R01CA112516]
- NIH [T32 CA009001]
Ask authors/readers for more resources
The NFB-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 (NFB)-dependent pathway. In this study, we investigated associations between 34 NFB1 and 8 IBK 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 IBK SNPs were associated with a statistically significant lower colorectal or colon cancer risk: rs9694958 (A > G intron 5) (colorectal: ORhzv 0.26(0.070.99), P-trend 0.048, P-adj 0.25), rs10958713 (A > C intron 19) (colon: ORhzv 0.62(0.420.92), P-trend 0.005, P-adj 0.03) and rs5029748 (C > A intron 2) (colon: ORhet 0.72(0.560.91), P-trend 0.01, P-adj 0.08). We replicated trends associated with NFB1 and IBK variants identified in a previous study (rs4648110 (T > A intron 22), rs13117745 (G > A intron 5) and rs3747811 (T > A intron 1)). IBK'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 NFB1'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 NFB1 and IBK are associated with CRC risk and NSAIDs may function partially through an NFB-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available