Abstract
BackgroundTranscription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC) risk. The aim of this study was to investigate if polymorphisms in nuclear factor kappa-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use.MethodsThe polymorphisms nuclear factor kappa-B (NFkB, NFKB1) -94 insertion/deletion ATTG (rs28362491), pregnane X receptor (PXR, NR1I2) A-24381C (rs1523127), C8055T (rs2276707), A7635G (rs6785049), liver X receptor (LXR-β, NR1H3) C-rs1405655T, T-rs2695121C were assessed together with lifestyle factors in a nested case-cohort study of 378 CRC cases and 756 random participants from the Danish prospective Diet, Cancer and Health study of 57,053 persons.ResultsCarriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR) = 1.45, 95% confidence interval (95% CI): 1.10-1.92). There was interaction between this polymorphism and intake of red and processed meat in relation to CRC risk. Carriers of NFkB -94deletion were at 3% increased risk pr 25 gram meat per day (95% CI: 0.98-1.09) whereas homozygous carriers of the insertion were not at increased risk (p for interaction = 0.03). PXR and LXR polymorphisms were not associated with CRC risk. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID) or smoking status and NFkB, PXR or LXR polymorphisms.ConclusionsA polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role for NFkB in CRC aetiology.
Highlights
Transcription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC) risk
We investigated the association between polymorphisms in nuclear factor kappa-B (NFkB) (NFkB1) -94 insertion/deletion ATTG, pregnane X receptor (PXR) (NR1I2) A-rs1523127-C, C-rs2276707-T, A-rs6785049-G, Liver X receptor (LXR) (NR1H2) C-rs1405655-T, T-rs2695121-C and risk of CRC, as well as interactions between genes and consumption of red and processed meat, smoking status and use of nonsteroid antiinflammatory drugs (NSAID) in relation to the development of CRC, in a case-cohort study nested in the prospective population-based Danish Diet, Cancer and Health study
Carriers of the NFkB -94del were at 1.45-fold (95% confidence interval (CI): 1.10-1.92) higher risk of CRC than homozygous carriers of the ins allele (Table 2) whereas PXR and LXR genotypes were not associated with CRC risk (Table 2)
Summary
Transcription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC) risk. The aim of this study was to investigate if polymorphisms in nuclear factor kappa-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. Intake of red and processed meat is a risk factor for CRC and Danes have the highest meat intake per capita in the World [1,3,4]. Red and processed meat represent sources of carcinogenic heterocyclic amines (HCA), polycyclic aromatic hydrocarbons (PAH) as well as N-nitroso. The expression of human MDR1 is regulated by pregnane X receptor (PXR) and nuclear factor-B (NFkB) [21] whereas other xenobiotic transporters such as ABCC2 (MRP2) seem to be regulated by PXR and Liver X receptor (LXR) and ABCG2 (BCRP) by Peroxisome Proliferator-Activated Receptor g (PPARg) [21,22,23,24]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
