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Background: Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked.Methods: Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale.Results: Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 μg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR = 1.1 per interquartile range difference [95% CI = 1.0, 1.2). In sex-stratified analyses, the association seemed restricted to men (aHR = 1.5 [95% CI = 1.2, 1.9]).Conclusions: In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men. [ABSTRACT FROM AUTHOR]

Background: Meat and dietary fiber are associated with increased and decreased risk of colorectal cancer (CRC), respectively. Toll-like receptors (TLRs) regulate the intestinal immune response in a complex interplay between the mucosal epithelium and the microbiota and may therefore be important modulators of diet-induced CRC together with other inflammatory mediators. Objective: Our aim was to investigate the association between functional TLR polymorphisms and risk of CRC and the interaction with dietary factors. Additionally, interactions with previously studied polymorphisms in IL10, IL1B, PTGS2, and NFKB1 were assessed in order to examine possible biological pathways in meat-induced CRC. Design: A nested case-cohort study of 897 CRC cases and 1689 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study encompassing 57,053 persons was performed using Cox proportional hazard models and the likelihood ratio test. Results: We found associations between polymorphisms in TLR2 (P = 0.018) and TLR4 (P = 0.044) and risk of CRC per se, interactions between intake of red and processed meat (10 g/d) and polymorphisms in TLR1 (P-interaction = 0.032) and TLR10 (P-interaction = 0.026 and 0.036), and intake of cereals (50 g/d) and TLR4 (P-interaction = 0.044) in relation to risk of CRC. Intake of red and processed meat also interacted with combinations of polymorphisms in TLR1 and TLR10 and polymorphisms in NFKB1, IL10, IL1B, and PTGS2 (P-interaction; TLR1/rs4833095 x PTGS2/rs20417 = 0.021, TLR10/rs11096955 x IL10/rs3024505 = 0.047, TLR10/rs11096955 x PTGS2/rs20417 = 0.017, TLR10/rs4129009 x NFKB1/rs28362491 = 0.027, TLR10/rs4129009 x IL1B/rs4848306 = 0.020, TLR10/rs4129009 x IL1B/rs1143623 = 0.021, TLR10/rs4129009 x PTGS2/rs20417 = 0.027), whereas intake of dietary fiber (10 g/d) interacted with combinations of polymorphisms in TLR4, IL10, and PTGS2 (P-interaction; TLR4/rs1554973 x IL10/rs3024505 = 0.0012, TLR4/rs1554973 x PTGS2/rs20417 = 0.0041, TLR4/rs1554973 x PTGS2/rs5275 = 0.0064). Conclusions: Our study suggests that meat intake may activate TLRs at the epithelial surface, leading to CRC via inflammation by nuclear transcription factor-κB-initiated transcription of inflammatory genes, whereas intake of fiber may protect against CRC via TLR4-mediated secretion of interleukin-10 and cyclooxygenase-2. Our results should be replicated in other prospective cohorts with well-characterized participants. The trial was registered at www.clinicaltrials.gov as NCT03250637. [ABSTRACT FROM AUTHOR]

Background and aims.The ATP-binding cassette (ABC) transporter family transports various molecules across the enterocytes in the gut protecting the intestine against potentially harmful substances. Moreover, ABC transporters are involved in mucosal immune defence through interaction with cytokines. The study aimed to assess whether polymorphisms inABCB1,ABCC2andABCG2were associated with risk of colorectal cancer (CRC) and to investigate gene–environment (dietary factors, smoking and use of non-steroidal anti-inflammatory drugs) and gene–gene interactions between previously studied polymorphisms inIL1BandIL10and ABC transporter genes in relation to CRC risk.Materials and methods.We used a Danish prospective case-cohort study of 1010 CRC cases and 1829 randomly selected participants from the Danish Diet, Cancer and Health cohort. Incidence rate ratios were calculated based on Cox’ proportional hazards model.Results.None of the polymorphisms were associated with CRC, butABCB1andABCG2haplotypes were associated with risk of CRC.ABCB1/rs1045642 interacted with intake of cereals and fiber (p-Value for interaction (Pint) = 0.001 and 0.01, respectively). In a three-way analysis, bothABCB1/rs1045642 andABCG2/rs2231137 in combination withIL10/rs3024505 interacted with fiber intake in relation to risk of CRC (Pint= 0.0007 and 0.009).Conclusions.Our results suggest that the ABC transporters P-glycoprotein/multidrug resistance 1 and BRCP, in cooperation with IL-10, are involved in the biological mechanism underlying the protective effect of fiber intake in relation to CRC. These results should be replicated in other cohorts to rule out chance findings. [ABSTRACT FROM PUBLISHER]

Background: Physical activity reduces, whereas exposure to air pollution increases, the risk of premature mortality. Physical activity amplifies respiratory uptake and deposition of air pollutants in the lung, which may augment acute harmful effects of air pollution during exercise. Objectives: We aimed to examine whether benefits of physical activity on mortality are moderated by long-term exposure to high air pollution levels in an urban setting. Methods: A total of 52,061 subjects (50-65 years of age) from the Danish Diet, Cancer, and Health cohort, living in Aarhus and Copenhagen, reported data on physical activity in 1993-1997 and were followed until 2010. High exposure to air pollution was defined as the upper 25th percentile of modeled nitrogen dioxide (NO2) levels at residential addresses. We associated participation in sports, cycling, gardening, and walking with total and cause-specific mortality by Cox regression, and introduced NO2 as an interaction term. Results: In total, 5,534 subjects died: 2,864 from cancer, 1,285 from cardiovascular disease, 354 from respiratory disease, and 122 from diabetes. Significant inverse associations of participation in sports, cycling, and gardening with total, cardiovascular, and diabetes mortality were not modified by NO2. Reductions in respiratory mortality associated with cycling and gardening were more pronounced among participants with moderate/low NO2 [hazard ratio (HR) = 0.55; 95% CI: 0.42, 0.72 and 0.55; 95% CI: 0.41, 0.73, respectively] than with high NO2 exposure (HR = 0.77; 95% CI: 0.54, 1.11 and HR = 0.81; 95% CI: 0.55, 1.18, p-interaction = 0.09 and 0.02, respectively). Conclusions: In general, exposure to high levels of traffic-related air pollution did not modify associations, indicating beneficial effects of physical activity on mortality. These novel findings require replication in other study populations. Citation: Andersen ZJ, de Nazelle A, Mendez MA, Garcia-Aymerich J, Hertel O, Tjшnneland A, Overvad K, Raaschou-Nielsen O, Nieuwenhuijsen MJ. 2015. A study of the combined effects of physical activity and air pollution on mortality in elderly urban residents: the Danish Diet, Cancer, and Health cohort. Environ Health Perspect 123:557-563; [ABSTRACT FROM AUTHOR]

Maintenance of a balance between commensal bacteria and the mucosal immune system is crucial and intestinal dysbiosis may be a key event in the pathogenesis of colorectal cancer (CRC). The toll-like receptor 4 (TLR4) is an important pattern-recognition receptor that regulates inflammation and barrier function in the gut by a mechanism that involves activation of the nuclear factor–κB (NF-κB) transcription factor. Dietary and life style factors may impact these functions. We therefore used a Danish prospective case-cohort study of 1010 CRC cases and 1829 randomly selected participants from the Danish Diet, Cancer and Health cohort to investigate three polymorphisms in NFKB1 and TLR4 and their possible interactions with diet and life style factors in relation to risk of CRC. Homozygous carriage of the variant allele of the TLR4/rs5030728 polymorphism was associated with increased risk of CRC (incidence rate ratio (IRR) = 1.30; 95% confidence interval (CI): 1.05–1.60; P = 0.02 (gene-dose model); IRR = 1.24; 95%CI: 1.01–1.51; P = 0.04 (recessive model)). Del-carriers of the NFKB1/rs28362491 polymorphism had a 17% (95%CI: 1.03–1.34; P = 0.02) increased risk of CRC compared to homozygous carriers of the ins-allele. However, none of these risk estimates withstood adjustment for multiple comparisons. We found no strong gene-environment interactions between the examined polymorphism and diet and life style factors in relation to CRC risk. [ABSTRACT FROM AUTHOR]

Background. A breast cancer diagnosis has been suggested as a teachable moment when a woman is more open to making healthier lifestyle changes. Little is known about the health behaviour changes women with breast cancer initiate compared to those made by other women. Material and methods. We examined changes in body mass index (BMI) and tobacco and alcohol consumption among women with a diagnosis of breast cancer and among cancer-free women. We used data from 23 420 women aged 50-64 years who participated in the Diet, Cancer and Health cohort, of whom 449 were diagnosed with breast cancer between baseline (1993-1997) and follow-up (2000-2002), and 22 971 remained cancer-free. We used multiple linear regression analysis to examine differences in BMI and alcohol and tobacco consumption between the two groups and to examine whether demographic and prognostic factors were associated with behavioural changes in women with breast cancer. Results. There were no significant differences in changes in BMI, alcohol and tobacco consumption between the two groups. Only in sub-analyses among women who lost weight between baseline and follow-up, women with breast cancer lost more weight than cancer-free women (β = 0.2; CI 0.1; 0.4), but residual confounding from stage cannot be excluded. Among the women with breast cancer we found no significant changes in BMI, alcohol and tobacco consumption by level of education, marital status, chemotherapy, hormone therapy or radiation. Conclusion. Women with breast cancer did not reduce their BMI, or modify their alcohol use or tobacco consumption compared with cancer-free women. This study indicates that guidelines and interventions to change health behaviour are needed after a cancer diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Organochlorines (OCs) are ubiquitously present in the environment, and food of animal origin is currently reported as the major source of exposure. Carcinogenicity in animals raises concern, and OCs may also be a risk factor for both neurological and immunological effects. Our primary objective was to study predictors of adipose tissue levels of dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs) in Danish women. We showed that adipose tissue concentrations of DDE and PCBs were consistently positively associated with age and the consumption of fish with a high fat content, while total lifetime duration of lactation had an inverse relationship. The direction of the association with body mass index (BMI) depended on the OC studied. The consumption of meat, fruit, lean fish, medium-fat-content fish, poultry, and eggs was not associated with OC concentrations in our study. We classified fish according to fat percentage, which seems more relevant than considering only total fish consumption. When PCBs were subdivided according to their chemical structure, similar results were obtained for the mono-, di-, and tri-ortho PCBs, indicating that PCBs can be treated as a homogenous group when studying predictors of concentrations in humans. In conclusion, the present study shows that age, lactation, and BMI are consistent predictors of human adipose tissue concentrations of DDE and PCBs and that dietary factors other than fish with a high fat content are not important predictors of these concentrations. [Copyright &y& Elsevier]

The mammalian lignan enterolactone (ENL), which is produced from dietary plant-lignan precursors by the intestinal microflora, may protect against breast cancer and other hormone-dependent cancers. This cross-sectional study examined which variables related to diet and lifestyle were associated with high plasma concentrations of ENL in Danish postmenopausal women. Plasma ENL was measured by time-resolved fluoroimmunoassay in 857 Danish women aged 50-64 y who participated in a prospective cohort study. Diet was assessed using a semiquantitative FFQ, and background information on lifestyle was collected using a self-administered questionnaire. Multiple analyses of covariance were completed in two steps. The median plasma ENL concentration was 27 nmol/L (range 0-455 nmol/L). In covariance analyses, positive associations were found between consumption of cereals, vegetables, and beverages and plasma ENL concentration. When analyzing subgroups of these food groups, the associations were confined to whole-grain products, cabbage, leafy vegetables, and coffee. For fat and the nondietary variables, negative associations between BMI, smoking, and frequency of bowel movements and plasma ENL concentration were observed. These data show that foods high in ENL precursors are associated with high concentrations of ENL. Furthermore, smoking, frequent bowel movements, and consumption of fat seems to have a negative affect on the ENL concentration. In conclusion, whole grains and vegetables are the most important dietary providers of plant lignans for the concentration of ENL in Danish postmenopausal women, and if ENL is found to protect against cancer or heart disease, the intake of whole grains and vegetables should be increased. [ABSTRACT FROM AUTHOR]

Studies the relation between wine drinking and the intake of selected food items by men and women in Denmark. Association of drinking preferences with a higher intake of fruit, fish, vegetables and salad; Lower proportion of wine drinkers who use fat spread on bread; Use of olive oil for cooking.

Presents information on a study which described the alcohol and drinking patterns among men and women in Denmark. Relation between alcohol intake and mortality; Materials and methods; Results and discussion; Conclusion.

Objective: The primary aim of the study was to evaluate the association between adipose tissue arachidonic acid (AA) content and the risk of myocardial infarction (MI). The secondary aim was to assess the correlation between adipose tissue AA and dietary intake of AA and linoleic acid (LA)., Methods: We conducted a case-cohort study nested within the Danish prospective Diet, Cancer and Health (DCH) study. After appropriate exclusions, the study included 2134 incident MI cases. Gluteal adipose tissue biopsies were collected at recruitment, and the fatty acid composition was determined by gas chromatography. A weighted Cox proportional hazards model was used to evaluate the association between adipose tissue AA content and the risk of MI., Results: After adjusting for confounders we found a positive association between adipose tissue AA content and the risk of MI. Hazard ratios (HR) of MI relative to the lowest quintile of adipose tissue AA content, increased across quintiles; second quintile (HR 1.19 95%CI: 0.97-1.45), third (HR 1.24 95%CI: 1.02-1.52), fourth (HR 1.28 95%CI: 1.03-1.60), and fifth quintile (HR 1.39 95%CI: 1.10-1.77). Adipose tissue AA levels were not correlated with dietary intake of AA (r=0.03, 95%CI: -0.01, 0.06) and weakly negatively correlated with dietary intake of LA (r=-0.12, 95%CI: -0.15, -0.08)., Conclusions: The adipose tissue content of AA was positively associated with the risk of MI but did not correlate with dietary intake of neither AA nor LA., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)