Interaction between interleukin-10 (IL-10) polymorphisms and dietary fibre in relation to risk of colorectal cancer in a Danish case-cohort study

<p>Abstract</p> <p>Background</p> <p>More than 50% of the colorectal cancer (CRC) etiology has been attributed to diet. Established or suspected dietary factors modifying risk of CRC are red meat, cereals, fish, and fibre. Diet and lifestyle may be linked to cancer through inflammation. Interleukin-10 (IL-10) is an anti-inflammatory cytokine. We wanted to test if dietary factors and <it>IL10</it> polymorphisms interact in relation to colorectal carcinogenesis.</p> <p>Methods</p> <p>The functional <it>IL10</it> polymorphism C-592A (rs1800872) and the marker rs3024505 were assessed in relation to diet and lifestyle in a nested case-cohort study of 378 CRC cases and 775 randomly selected participants from a prospective study of 57,053 persons. Genotyping data on the <it>IL10</it> polymorphism C-592A, smoking and non-steroidal anti-inflammatory drugs (NSAID) was retrieved from Vogel et al. (Mutat Res, 2007; 624:88). Incidence rate ratios (IRR) and 95% Confidence Interval (95% CI) were calculated.</p> <p>Results</p> <p>No associations were found between the <it>IL10</it> rs3024505 polymorphism and risk of CRC. There was interaction between rs3024505 and dietary fibre (P-value for interaction = 0.01). <it>IL10</it> rs3024505 homozygous wildtype carriers were at 27% reduced risk of CRC per 10 g fibre per day (95% CI: 0.60-0.88) whereas variant carriers had no risk reduction by fibre intake. Also, interaction between <it>IL10</it> C-592A and intake of fibre was found (P-value for interaction = 0.02). Among those eating <17.0 grams of fibre per day, carriers of an C-592A variant allele had a statistically significantly higher risk of colorectal cancer compared to homozygous wildtypes. No significant differences in colorectal cancer risk were observed between the reference group (CC and <17.0 g/day) and carriers of one C-592A variant allele eating 17.0 or more grams of dietary fibre per day. This suggests that the increased risk due to carrying the variant allele can be overcome by higher fibre intake. No interactions between <it>IL10</it> polymorphisms and dietary meat, cereal, or fish intake, or between <it>IL10</it> rs3024505 and smoking or NSAID use were found.</p> <p>Conclusions</p> <p>In this northern Caucasian cohort we found interaction between <it>IL10</it> and dietary fibre in CRC carcinogenesis. High intake of fibre seems to protect against CRC among individuals with <it>IL10</it> related genetic susceptibility to CRC. This finding should be evaluated in other prospective and population-based cohorts with different ethnic groups.</p

Meat consumption and mortality -results from the European Prospective Investigation into Cancer and Nutrition

Abstract Background: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. Results: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and &apos;other causes of death&apos;. The consumption of poultry was not related to all-cause mortality. Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer

Real-world dose adjustments of biologic treatments in psoriasis and their economic impact : a Swedish national population study

Background To date, evidence on the dose adjustments of biologics in the real-world treatment of psoriasis is limited. However, dose adjustments may have important clinical and economic implications. Aims To study the dose adjustments of individual biologics over time in real-world practice in Sweden. Methods A retrospective observational study of adults with moderate to severe psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Treatment episodes were identified for individual patients from the date of drug dispensation to the end of the supply of the drug. Dosing data were expressed as the proportion of treatment episodes with accumulated syringes/vials equal to, above or below the recommended guidelines. Real-world costs were calculated and compared with costs predicted from dosing guidelines. Results The mean dose was above recommended levels for all biologics investigated. Weighted mean dose adjustments for adalimumab, etanercept, secukinumab and ustekinumab were 13%, 23%, 8% and 3%, respectively, over the entire treatment period. Higher doses translate to higher costs, including notable increases over time vs. expected costs for secukinumab. Conclusions Dose adjustments of biologics are frequent in clinical practice but differ for the various biologics. The mean observed increases in dose above guideline recommendations might indicate perceptions of suboptimal efficacy for biologics, with implications for the cost and cost-effectiveness of these treatments. Further research is warranted to understand the reasons for dose adjustments in clinical practice.Funding Agencies|LEO Pharma A/S</p