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

Treatment Delay in Oral and Oropharyngeal Cancer in Our Population: The Role of Socio-Economic Factors and Health-Seeking Behaviour

The objective is to assess the role of socio-economic factors and health-seeking behavior in treatment delay in oral and oropharyngeal cancer in our population. This article adapts—design: prospective study and setting: tertiary care centre. We studied 153 patients with oral and oropharyngeal squamous cell carcinoma who were managed in the department of otolaryngology and head and neck surgery between January 2006 and December 2007. There were 127 male patients (83%) and 26 females (17%) with ages ranging from 22 years to 70 years. Fifty-nine patients (39%) presented to us with early stage disease (i.e. stage I and II), whereas, 94 patients (61%) presented with late stage disease (i.e. stage III and IV). Of the 59 patients presenting with early stage disease, 20 were illiterate and 39 literate with 28 patients (47%) belonging to low socio-economic status and 32 patients (54%) having an access to primary health centre (PHC). Of the 94 patients presenting with late stage disease, 53 were illiterate and 41 literate with 58 patients (62%) belonging to low socio-economic status and 38 patients (40%) having an access to primary health centre. Literacy, socio-economic status, access to primary health centre and health-seeking behavior of our population has a significant association with the stage of presentation of patients with oral and oropharyngeal cancer