Intake of heterocyclic aromatic amines and the risk of prostate cancer in the EPIC-Heidelberg cohort

Background: Heterocyclic amines (HCA) are positively associated with prostate cancer risk in animal models. Because of mostly inconsistent results of epidemiological studies, we examined the association between intake of HCA and prostate cancer risk. Methods: In the EPIC-Heidelberg cohort, detailed information on diet, anthropometry, and lifestyle was assessed between 1994 and 1998. Dietary HCA intake was estimated using information on meat consumption, cooking methods, and preferred degree of browning. During 104,195 person-years of follow-up, 337 incident cases of prostate cancer (123 advanced cases) were identified among 9,578 men with valid dietary information. Multivariate Cox proportional hazards regression was used to examine the association between intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and prostate cancer. Results: Men in the highest quartiles of PhIP, MeIQx, and DiMeIQx intake, respectively, had no increased risk of prostate cancer compared with men in the lowest quartiles (HR=0.89, 95% CI 0.66-1.22 [PhIP]; 1.06, 0.77-1.45 [MeIQx]; 0.98, 0.72-1.34 [DiMeIQx]). There were no associations between HCA intake and advanced prostate cancer or between high consumption of strongly browned meat and prostate cancer. Discussion: Our data do not support the hypothesis that HCA intake as consumed in a regular diet is a risk factor for prostate cance

Asthma and the risk of gastrointestinal disorders: a Mendelian randomization study

BACKGROUND: The question of whether asthma is causally related to gastrointestinal disorders remained unanswered so far. Thus, this study investigated whether there is such a relation and whether the time of onset of asthma plays a role in the occurrence of the following gastrointestinal disorders: peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) including the distinction between Crohn’s disease (CD) and ulcerative colitis (UC). METHODS: Using summary data of genome-wide association studies (GWASs), we ran Mendelian randomization analyses based on up to 456,327 European participants. Outlier assessment, a series of sensitivity analyses and validation of IBD results in a second GWAS were performed to confirm the results. RESULTS: Presented ORs represent the average change in the outcome per 2.72-fold increase in the prevalence of the exposure. Genetically predicted childhood-onset asthma was positively associated with PUD, GORD, and IBS with similar odds ratios near 1.003 and adjusted P-values from 0.007 (GORD) to 0.047 (PUD). Furthermore, it was inversely related to IBD (OR = 0.992, 95% CI: 0.986, 0.998, adjusted P = 0.023) and suggestively associated with its UC subtype (OR = 0.990, 95% CI: 0.982, 0.998, adjusted P = 0.059). There were no associations between genetically predicted adult-onset asthma and the mentioned gastrointestinal disorders. CONCLUSIONS: This study provides evidence that the presence of asthma onset in childhood increases the risk for GORD, PUD, and IBS but decreases the risk for IBD in adults. The lower risk for IBD may be attributed to a lower risk primarily for UC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02283-7

Causal relationship between dietary macronutrient composition and anthropometric measures: a bidirectional two-sample Mendelian randomization analysis

Background: The question whether the proportion of energy provided by fat and carbohydrates in the diet is associated with body mass index (BMI) and waist circumference (WC) is an important public health issue, but determining causality is difficult in epidemiological studies. Objectives: Using a two-sample bidirectional Mendelian randomization (MR) in both a univariable and multivariable setting, we aimed to determine whether the relative proportion of different macronutrients in the diet (in % of total energy intake (E%)) is causally related to BMI and WC and vice versa. Methods: All analyses were based on genome-wide association studies including 268,922 Europeans with dietary data (SSGAC Consortium) and at least 232,101 with anthropometric measures (GIANT Consortium). An inverse-variance weighted approach using modified second-order weights within the radial regression framework was performed. Radial MR-Egger, weighted median and mode, Robust Adjusted Profile Score (RAPS), and Pleiotropy RESidual Sum and Outlier (PRESSO) methods were used in sensitivity analyses to verify MR assumptions. Additionally, multivariable MR was conducted to account for inter correlation between macronutrient intakes. All estimates represent the standard deviation (SD) change in each outcome per one SD change in the respective exposure. Results: We found that genetically predicted relative carbohydrate intake (E%) reduced BMI (β = −0.529; 95% CI: −0.745, −0.312; P-value = 2⋅10−6) and WC (β = −0.459; 95% CI: −0.656, −0.262; P-value = 5⋅10−6). Both effects were also supported by the multivariable approach: β = −0.441 (95% CI: −0.772, −0.109; P-value = 0.009) for BMI and β = −0.410 (95% CI: −0.667, −0.154; P-value = 0.002) for WC. Genetically predicted dietary intake of fat (E%) was weaker and positively related to both anthropometric measures. We obtained evidence that a higher BMI and WC increased the relative dietary intake of fat and protein (E%). For example, each SD higher BMI increased protein intake (E%) by 0.114 SD (95% CI: 0.081, 0.147; P-value = 9⋅10−12) and each SD higher WC increased protein intake (E%) by 0.078 SD (95% CI: 0.035, 0.121; P-value = 4⋅10−4). Sensitivity analyses confirmed these findings revealing consistent effect estimates. Conclusions: Using genetic information to improve causal inference we found evidence, that a low relative carbohydrate proportion (E%) and a high proportion of fat (E%) in the diet is causally related to a higher BMI and a higher WC. Further research considering carbohydrate, fat, and protein quality and possible consequences on micronutrient intake is needed to define the implications for dietary intake recommendations

Associations between anthropometric parameters and immune-phenotypical characteristics of circulating Tregs and serum cytokines

Objective To investigate the associations between several anthropometric parameters and regulatory T cells (Tregs) and circulating cytokines in a population-based cohort. Methods Between 2018 and 2021, a total of 238 participants were examined up to three times within the scope of the MEGA study in Augsburg, Germany. Tregs were analyzed using flow cytometry and the serum concentrations of 52 cytokines were determined. Anthropometric parameters were measured, using also bioelectrical impedance analysis: body mass index (BMI), relative total body fat, relative visceral adipose tissue (rVAT), waist circumference (WC), waist-to-hip ratio (WHR) and body fat distribution. Associations were analyzed using linear mixed models with random intercept (Tregs) and conventional linear regression models (cytokines). Results WC and WHR were inversely associated with the general Treg subset. Four parameters (BMI, rVAT, WC, and WHR) were inversely associated with the conventional Treg population. Three cytokines showed a particularly strong association with several anthropometric parameters: the cutaneous T-cell attracting chemokine was inversely associated with anthropometric parameters, while hepatocyte growth factor and interleukine-18 showed positive associations. Conclusions Anthropometric measures are associated with Tregs and serum cytokine concentrations revealing new important interconnections between obesity and the adaptive immune system

Dietary calcium and magnesium intake in relation to cancer incidence and mortality in a German prospective cohort (EPIC-Heidelberg)

To prospectively evaluate the associations of dietary calcium and magnesium intake with cancer incidence and mortality, data of 24,323 participants of the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg), who were aged 35-64years and cancer-free at recruitment (1994-1998), were analyzed using multivariate Cox regression models. After an average follow-up time of 11years, 2,050 incident cancers were diagnosed and 513 cancer deaths occurred. Dietary calcium intake was inversely but not statistically significantly associated with colorectal cancer risk (hazard ratio [HR] for per 100mg increase in intake: 0.95; 95% confidence interval [CI]: 0.88, 1.02) and lung cancer risk (HR for per 100mg increase in intake: 0.94; 95% CI: 0.87, 1.02). No statistically significant associations were observed between dietary calcium intake and site-specific or overall cancer incidence or mortality. Dietary magnesium intake was not statistically significantly associated with any of the investigated outcomes. This prospective cohort study provides no strong evidence to support that high dietary calcium and magnesium intake in the intake range observed in a German population may reduce cancer incidence or mortalit

Consistency of vitamin and/or mineral supplement use and demographic, lifestyle and health-status predictors: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort

Cross-sectional studies suggest that dietary supplement use is associated with favourable demographic and lifestyle factors and certain health conditions. However, factors that affect the consistency of supplement use have not been investigated in prospective cohort studies. The aim of the present study was to seek baseline demographic, lifestyle and health-status predictors of subsequent consistent vitamin and/or mineral supplement use. A total of 8968 men and 10672 women of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort, who answered the supplement-use questions in the baseline survey and two follow-up surveys, were categorised into three groups: consistent, inconsistent and never users. At baseline, 28·5% of men and 38·6% of women reported vitamin and/or mineral supplement use. After a median follow-up of 8·5 years, 14·6% of men and 22·9% of women were consistent users. During follow-up, 36·0% of male and 26·6% of female initial users stopped supplement use, whereas 27·8% of male and 39·4% of female initial non-users started supplement use. Women were more likely to be consistent users than men. Older age (≥50 years), lower BMI (<25kg/m2) and self-reported hyperlipidaemia were common predictors of consistent use for both sexes. Additional predictors included higher educational level for men, and being more physically active and higher lifetime alcohol consumption for women. Consistent users had the highest intake of dairy products, fish, fruits and vegetables, and wine but the lowest intake of total meat. We concluded that supplement use is a fairly unstable behaviour in free-living individuals. Individuals with a favourable lifestyle and healthier diet are more likely to show consistent supplementatio

Association between dietary factors and plasma fetuin-A concentrations in the general population

Circulating fetuin-A, a novel marker for hepatic fat accumulation, has been related to a higher risk of type 2 diabetes and cardiovascular diseases in a growing number of prospective studies. However, little is known about dietary determinants of fetuin-A concentrations in the general population. Therefore, we aimed to investigate the association between dietary intake of energy, energy-providing nutrients, alcohol and major food groups and plasma fetuin-A concentrations in the Bavarian Food Consumption Survey II. Dietary intake was assessed by three 24-h dietary recalls, and plasma concentrations of fetuin-A were measured in 558 adults (18-81 years). After multivariable adjustment for lifestyle factors and body fatness, higher energy intake was nonsignificantly associated with higher fetuin-A concentrations (per 2092 kJ/d (500 kcal/d) 3&middot;7 &micro;g/ml, 95 % CI -0&middot;5, 7&middot;8 &micro;g/ml). There was no clear association between energy-providing nutrients and fetuin-A concentrations. Higher alcohol intake was associated with lower fetuin-A concentrations (P trend 0&middot;003): mean fetuin-A concentrations were 324 (95 % CI 313, 335) &micro;g/ml in non-drinkers, and with 293 (95 % CI 281, 306) &micro;g/ml significantly lower in participants who drank &ge;30 g alcohol per d. Mean fetuin-A concentrations decreased across quintiles of milk and dairy product intake (lowest quintile 319 (95 % CI 309, 330) &micro;g/ml; highest quintile 304 (95 % CI 293, 314) &micro;g/ml; P trend 0&middot;03), and each 150-g increment in milk/dairy products per d was associated with 5&middot;6 (95 % CI -9&middot;6, -1&middot;5) &micro;g/ml lower fetuin-A. Dietary intakes of vegetables, meat or fish were not associated with fetuin-A concentrations. Because of the preventive potential of our findings, further exploration is warranted

Vitamin/mineral supplementation and cancer, cardiovascular, and all-cause mortality in a German prospective cohort (EPIC-Heidelberg)

Purpose: To prospectively evaluate the association of vitamin/mineral supplementation with cancer, cardiovascular, and all-cause mortality. Methods: In the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg), which was recruited in 1994-1998, 23,943 participants without pre-existing cancer and myocardial infarction/stroke at baseline were included in the analyses. Vitamin/mineral supplementation was assessed at baseline and during follow-up. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: After an average follow-up time of 11years, 1,101 deaths were documented (cancer deaths=513 and cardiovascular deaths=264). After adjustment for potential confounders, neither any vitamin/mineral supplementation nor multivitamin supplementation at baseline was statistically significantly associated with cancer, cardiovascular, or all-cause mortality. However, baseline users of antioxidant vitamin supplements had a significantly reduced risk of cancer mortality (HR: 0.52; 95% CI: 0.28, 0.97) and all-cause mortality (HR: 0.58; 95% CI: 0.38, 0.88). In comparison with never users, baseline non-users who started taking vitamin/mineral supplements during follow-up had significantly increased risks of cancer mortality (HR: 1.74; 95% CI: 1.09, 2.77) and all-cause mortality (HR: 1.58; 95% CI: 1.17, 2.14). Conclusions: Based on limited numbers of users and cases, this cohort study suggests that supplementation of antioxidant vitamins might possibly reduce cancer and all-cause mortality. The significantly increased risks of cancer and all-cause mortality among baseline non-users who started taking supplements during follow-up may suggest a "sick-user effect,” which researchers should be cautious of in future observational studie