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

Polymorphisms in NF-kappa B, PXR, LXR, PPAR gamma and risk of inflammatory bowel disease

AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD). METHODS: Genotypes of nuclear factor (NF)-kappa B (NFKB1) NF kappa B -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-gamma (PPAR gamma) PPAR gamma Pro12Ala (rs 1801282) and C1431T (rs 3856806); pregnane X receptor (PXR) (NR1I2) PXR A-24381C (rs1523127), C8055T (2276707), and A7635G (rs 6785049); and liver X receptor (LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn's disease patients, 495 ulcerative colitis (UC) patients, and 779 healthy controls. Odds ratio (OR) and 95% CI were estimated by logistic regression models. RESULTS: The PXR A7635G variant, the PPAR gamma Pro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC (OR: 1.31, 95% CI: 1.03-1.66, P = 0.03, OR: 2.30, 95% CI: 1.04-5.08, P = 0.04, and OR: 1.41, 95% CI: 1.00-1.98, P = 0.05, respectively) compared to the corresponding homozygous wild-type genotypes. Among never smokers, PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD (OR: 1.41, 95% CI: 1.05-1.91, P = 0.02, OR: 1.63, 95% CI: 1.21-2.20, P = 0.001, and OR: 2.02, 95% CI: 1.36-2.99, P = 0.0005, respectively) compared to the respective homozygous variant genotypes. PXR A7635G (rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease (OR: 1.34, 95% CI: 1.03-1.75 and OR: 2.49, 95% CI: 1.24-5.03, respectively). CONCLUSION: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers. (C) 2011 Baishideng. All rights reserved

Higher habitual flavonoid intakes are associated with a lower risk of peripheral artery disease hospitalizations

Background The role of nutrition in the primary prevention of peripheral artery disease (PAD), the third leading cause of atherosclerotic cardiovascular disease, is undetermined. Flavonoids may attenuate atherosclerosis and therefore persons who consume flavonoid-rich foods may have a lower risk of developing PAD. Objectives We aimed to examine the association between flavonoid intake and PAD hospitalizations and investigate if the association differs according to established risk factors for PAD. Methods Baseline data from 55,647 participants of the Danish Diet, Cancer, and Health Study without PAD, recruited from 1993 to 1997, were cross-linked with Danish nationwide registries. Flavonoid intake was calculated from FFQs using the Phenol-Explorer database. Associations were examined using multivariable-adjusted restricted cubic splines based on Cox proportional hazards models. Results After a median [IQR] follow-up time of 21 [20–22] y, 2131 participants had been hospitalized for any PAD. The association between total flavonoid intake and total PAD hospitalizations was nonlinear, reaching a plateau at ∼750–1000 mg/d. Compared with the median flavonoid intake in quintile 1 (174 mg/d), an intake of 1000 mg/d was associated with a 32% lower risk of any PAD hospitalization (HR: 0.68; 95% CI: 0.60, 0.77), a 26% lower risk of atherosclerosis (HR: 0.74; 95% CI: 0.62, 0.88), a 28% lower risk of an aneurysm (HR: 0.72; 95% CI: 0.59, 0.88), and a 47% lower risk of a hospitalization for other peripheral vascular disease (HR: 0.53; 95% CI: 0.42, 0.67). A higher total flavonoid intake was also significantly associated with a lower incidence of revascularization or endovascular surgery and lower extremity amputation. The association between total flavonoid intake and PAD hospitalizations differed according to baseline smoking status, alcohol intake, BMI, and diabetes status. Conclusions Ensuring the adequate consumption of flavonoid-rich foods, particularly in subpopulations prone to the development of atherosclerosis, may be a key strategy to lower the risk of PAD

Rye and health - Where do we stand and where do we go?

Background: High whole grain intake has consistently been associated with lowered risk of developing a number of chronic diseases. Among cereals, rye has highest content of dietary fiber, together with a wide variety of bioactive compounds. There is accumulating evidence from intervention studies of physiological effects of rye foods with potential health benefits. Scope and approach: This review summarizes the state of the art of rye and health and identifies future directions for research and innovation, based partly on findings presented at the international conference "The Power of Rye", angstrom land, Finland, 7-8 June 2017. Key findings and conclusions: Rye foods have well-established beneficial effects on insulin metabolism compared with wheat bread under isocaloric conditions and at standardized amounts of available carbohydrates, which may have positive implications for diabetes prevention. Recent findings suggest that alterations in blood glucose flux partly explain these effects. Moreover, several studies have shown beneficial effects of rye-based foods on satiety, which is one plausible mechanism behind recently demonstrated beneficial effects on weight management. Emerging results indicate beneficial effects of rye intake on inflammation and blood lipids. More research is needed to uncover underlying mechanisms for other demonstrated effects and the long-term implications for health. A challenge with rye-based foods is making them palatable and widely acceptable to consumers. Development of innovative and tasty rye products and targeted communication strategies is crucial in increasing awareness and consumption of rye foods. Novel results in this regard are presented in this review.Peer reviewe

Carbohydrate Intake in the Etiology of Crohn's Disease and Ulcerative Colitis

Background: Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC). Methods: A total of 401,326 men and women were recruited between 1991 and 1998. At recruitment, dietary intakes of carbohydrate, sugar, and starch were measured using validated food frequency questionnaires. The cohort was monitored identifying participants who developed incident CD or UC. Cases were matched with 4 controls, and odds ratios were calculated for quintiles of total carbohydrate, sugar, and starch intakes adjusted for total energy intake, body mass index, and smoking. Results: One hundred ten participants developed CD, and 244 participants developed UC during follow-up. The adjusted odds ratio for the highest versus the lowest quintiles of total carbohydrate intake for CD was 0.87, 95% CI = 0.24 to 3.12 and for UC 1.46, 95% CI = 0.62 to 3.46, with no significant trends across quintiles for either (CD, Ptrend = 0.70; UC, Ptrend = 0.41). Similarly, no associations were observed with intakes of total sugar (CD, Ptrend = 0.50; UC, Ptrend = 0.71) or starch (CD, Ptrend = 0.69; UC, Ptrend = 0.17). Conclusions: The lack of associations with these nutrients is in agreement with many case–control studies that have not identified associations with CD or UC. As there is biological plausibility for how specific carbohydrates could have an etiological role in inflammatory bowel disease, future epidemiological work should assess individual carbohydrates, although there does not seem to be a macronutrient effect

Changes in Waist Circumference and the Incidence of Acute Myocardial Infarction in Middle-Aged Men and Women

BACKGROUND: Waist circumference (WC) measured at one point in time is positively associated with the risk of acute myocardial infarction (MI), but the association with changes in WC (DWC) is not clear. We investigated the association between DWC and the risk of MI in middle-aged men and women, and evaluated the influence from concurrent changes in BMI (DBMI). METHODOLOGY/PRINCIPAL FINDINGS: Data on 38,593 participants from the Danish Diet, Cancer and Health study was analysed. Anthropometry was assessed in 1993-97 and 1999-02. Information on fatal and non-fatal MI was obtained from National Registers. Cases were validated by review of the medical records. Hazard ratios (HR) were calculated from Cox proportional hazard models with individuals considered at risk from 1999-02 until December 30 2009. During 8.4 years of follow-up, 1,041 incident cases of MI occurred. WC was positively associated with the risk of MI, but weakly after adjustment for BMI. DWC was not associated with the risk of MI (HR per 5 cm change = 1.01 (0.95, 1.09) with adjustment for covariates, baseline WC, BMI and DBMI). Associations with DWC were not notably different in sub-groups stratified according to baseline WC or DBMI, or when individuals with MI occurring within the first years of follow-up were excluded. CONCLUSIONS/SIGNIFICANCE: WC was positively associated with the risk of MI in middle-aged men and women, but changes in WC were not. These findings suggest that a reduction in WC may be an insufficient target for prevention of MI in middle-aged men and women

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

Alcohol consumption and mortality in individuals with diabetes mellitus

Studies have suggested that moderate alcohol consumption is associated with a reduced risk of CVD and premature mortality in individuals with diabetes mellitus. However, history of alcohol consumption has hardly been taken into account. We investigated the association between current alcohol consumption and mortality in men and women with diabetes mellitus accounting for past alcohol consumption. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was defined of 4797 participants with a confirmed diagnosis of diabetes mellitus. Men and women were assigned to categories of baseline and past alcohol consumption. Hazard ratios (HR) and 95% CI for total mortality were estimated with multivariable Cox regression models, using light alcohol consumption (>0-6 g/d) as the reference category. Compared with light alcohol consumption, no relationship was observed between consumption of 6 g/d or more and total mortality. HR for >6.12 g/d was 0.89(95% CI 0.61, 1.30) in men and 0.86(95% CI 0.46, 1.60) in women. Adjustment for past alcohol consumption did not change the estimates substantially. In individuals who at baseline reported abstaining from alcohol, mortality rates were increased relative to light consumers: HR was 1.52 (95% CI 0.99, 2.35) in men and 1.81 (95% CI 1.04, 3.17) in women. The present study in diabetic individuals showed no association between current alcohol consumption >6 g/d and mortality risk compared with light consumption. The increased mortality risk among non-consumers appeared to be affected by their past alcohol consumption rather than their current abstinence

PPARγ Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

<p>Abstract</p> <p>Background</p> <p>Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism <it>PPARγ2 </it>Pro¹²Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPARγ activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine.</p> <p>Methods</p> <p>A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals.</p> <p>Results</p> <p>Homozygous male variant allele carriers of <it>PPARγ2 </it>Pro¹²Ala were at higher risk of ACS (HR = 2.12, 95% CI: 1.00–4.48) than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5–38.7) compared to homozygous common allele carriers (p for interaction < 0.0001). Overall, the association was only observed among homozygous variant allele carriers. Thus, all the observed associations were obtained in subgroups including small numbers of cases. It is therefore possible that the observed associations were due to chance.</p> <p>Conclusion</p> <p>In the present study, there were no consistent associations between PPARγ Pro¹²Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.</p