Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>The polymorphisms nuclear factor kappa-B (<it>NFkB, NFKB1) </it>-94 insertion/deletion ATTG (rs28362491), pregnane X receptor (<it>PXR, NR1I2) </it>A-24381C (rs1523127), C8055T (rs2276707), A7635G (rs6785049), liver X receptor (<it>LXR-β, NR1H3) </it>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.</p> <p>Results</p> <p>Carriers of <it>NFkB </it>-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 <it>NFkB </it>-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). <it>PXR </it>and <it>LXR </it>polymorphisms were not associated with CRC risk. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID) or smoking status and <it>NFkB</it>, <it>PXR </it>or <it>LXR </it>polymorphisms.</p> <p>Conclusions</p> <p>A polymorphism in <it>NFkB </it>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.</p

Rate coefficients for the chemical reactions of CH₂F₂, CHClF₂, CH₂FCF₃ and CH₃CCl₃ with O(¹D) at 298 K

The rate coefficients for the chemical reactions (species loss rates, quenching excluded) of the refrigerants CH2F2 (HFC-32), CHClF2 (HFC-22) and CH2FCF3 (HFC-134a), and the solvent CH3CCl3 with O(D-1) are determined relative to CH4 + O(D-1) at 298 K. The resulting rates k(CH2F2 + O(D-1)) = (4.78 +/- 1.03) x 10 (11) cm(3) molecule (1) s (1), k(CHClF2 + O(D-1)) = (8.69 +/- 1.72) x 10 (11) cm(3) molecule (1) s (1), k(CH2FCF3 + O(D-1)) = (6.10 +/- 1.43) x 10 (11) cm(3) molecule (1) s (1) are compared to available literature data. The reaction rate of 1,1,1-trichloroethane with O(D-1) is determined for the first time, k(CH3CCl3 + O(D-1)) = (2.93 +/- 1.20) x 10 (10) cm(3) molecule (1) s (1)

Pressure dependence of the deuterium isotope effect in the photolysis of formaldehyde by ultraviolet light

The pressure dependence of the relative photolysis rate of HCHO vs. HCDO has been investigated for the first time, using a photochemical reactor at the University of Copenhagen. The dissociation of HCHO vs. HCDO using a UVA lamp was measured at total bath gas pressures of 50, 200, 400, 600 and 1030 mbar. The products of formaldehyde photodissociation are either H&lt;sub&gt;2&lt;/sub&gt; + CO (molecular channel) or HCO + H (radical channel), and a photolysis lamp was chosen to emit light at wavelengths that greatly favor the molecular channel. The isotope effect in the dissociation, &lt;i&gt;k&lt;/i&gt;&lt;sub&gt;HCHO&lt;/sub&gt;/&lt;i&gt;k&lt;/i&gt;&lt;sub&gt;HCDO&lt;/sub&gt;, was found to depend strongly on pressure, varying from 1.1 + 0.15/&amp;minus;0.1 at 50 mbar to 1.75&amp;plusmn;0.10 at 1030 mbar. The results can be corrected for radical channel contribution to yield the kinetic isotope effect for the molecular channel; i.e. the KIE in the production of molecular hydrogen. This is done and the results at 1030 mbar are discussed in relation to previous studies at ambient pressure. In the atmosphere the relative importance of the two product channels changes with altitude as a result of changes in pressure and actinic flux. The study demonstrates that the δD of photochemical hydrogen produced from formaldehyde will increase substantially as pressure decreases