Abstract
Background and Aims
We aimed to investigate the association between protein intake and risk of inflammatory bowel disease IBD in the European Prospective Investigation into Cancer and ...Nutrition.
Methods
A total of 413 593 participants from eight European countries were included. Dietary data were collected at baseline from validated food frequency questionnaires. Dietary data were calibrated to correct errors in measures related to each country-specific questionnaire. Associations between proteins total, animal, and vegetable or food sources of animal proteins, and IBD risk were estimated by Cox proportional hazard models.
Results
After a mean follow-up of 16 years, 177 patients with Crohn’s disease CD and 418 with ulcerative colitis UC, were identified. There was no association between total protein, animal protein, or vegetable protein intakes and CD or UC risks. Total meat and red meat intakes were associated with UC risk (hazard ratio HR for the 4th vs 1st quartile = 1.40, 95% confidence interval CI = 0.99-1.98, p-trend = 0.01; and 1.61, 95% CI = 1.10-2.36, p-trend = 0.007, respectively. There was no association between other food sources of animal protein processed meat, fish, shellfish, eggs, poultry and UC. We found no association between food sources of animal proteins and CD risk.
Conclusions
Meat and red meat consumptions are associated with higher risks of UC. These results support dietary counselling of low meat intake in people at high-risk of IBD.
Graphical Abstract
Graphical Abstract
Gallstones are common disorders associated with several cardiovascular risk factors. Gallstone formation and atherosclerosis may share key pathways, but studies on putative associations between ...gallstones and the risk of cardiovascular disease are sparse and non-conclusive. We studied the relationship between gallstones and the risk of subsequent cardiovascular diseases in the German arm of the European Prospective Investigation into Cancer and Nutrition (EPIC).
The study comprises 46,468 participants from EPIC-Potsdam and EPIC-Heidelberg aged 35-65 years, free of cardiovascular diseases and diabetes at baseline. Information about the gallstone status at baseline was ascertained via questionnaires. For all incident cases of myocardial infarction and stroke confirmation was obtained from the treating physician. Relative risks were estimated using Cox proportional hazards regression.
During eight years of follow-up, 919 participants suffered a stroke or myocardial infarction. After multivariable adjustment for established risk factors, subjects with reported gallstones (n = 4828) had an increased risk of cardiovascular diseases (hazard rate ratio (HR) = 1.24, 95% confidence interval (CI): 1.02, 1.50). In individuals, who underwent a cholecystectomy before baseline a 1.32-fold increase in risk was observed (95%CI: 1.05, 1.65). HRs differed depending on the presence of selected established risk factors (e.g. HR for cardiovascular diseases regarding gallstones in smokers = 1.66, 95%CI: 1.20, 2.30, and non-smokers = 1.09, 95%CI: 0.86, 1.38).
Our results indicate an increased cardiovascular risk for gallstone formers, which cannot be counteracted by gallbladder removal and opens up perspectives for individualized prevention strategies.
Earlier epidemiological studies indicate that associations between obesity and breast cancer risk may not only depend on menopausal status and use of exogenous hormones, but might also differ by ...tumor subtype. Here, we evaluated whether obesity is differentially associated with the risk of breast tumor subtypes, as defined by 6 immunohistochemical markers (ER, PR, HER2, Ki67, Bcl-2 and p53, separately and combined), in the prospective EPIC-Germany Study (n = 27,012).
Formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 657 incident breast cancer cases were used for histopathological analyses. Associations between BMI and breast cancer risk across subtypes were evaluated by multivariable Cox regression models stratified by menopausal status and hormone therapy (HT) use.
Among postmenopausal non-users of HT, higher BMI was significantly associated with an increased risk of less aggressive, i.e. ER+, PR+, HER2-, Ki67
, Bcl-2+ and p53- tumors (HR per 5 kg/m
: 1.44 1.10, 1.90, p = 0.009), but not with risk of more aggressive tumor subtypes. Among postmenopausal users of HT, BMI was significantly inversely associated with less aggressive tumors (HR per 5 kg/m
: 0.68 0.50, 0.94, p = 0.018). Finally, among pre- and perimenopausal women, Cox regression models did not reveal significant linear associations between BMI and risk of any tumor subtype, although analyses by BMI tertiles showed a significantly lower risk of less aggressive tumors for women in the highest tertile (HR: 0.55 0.33, 0.93).
Overall, our results suggest that obesity is related to risk of breast tumors with lower aggressiveness, a finding that requires replication in larger-scale analyses of pooled prospective data.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are ...limited. We investigated the association between prediagnostic intake of these foods and dietary calcium, and the subsequent development of Crohn's disease (CD) and ulcerative colitis (UC).
In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, and cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n = 110) or UC (n = 244) during follow-up were matched with 4 controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking.
Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI, 0.32-1.19, p trend = 0.19) and 0.63 (95% CI, 0.28-1.42, p trend = 0.23) for CD, and 0.80 (95% CI, 0.50-1.30, p trend = 0.40) and 0.81 (95% CI, 0.49-1.34, p trend = 0.60) for UC, respectively. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI, 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI, 0.49-1.47).
Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect.
Summary
Background
Nutri‐score is now widely available in food packages in Europe.
Aim
To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative ...colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
Methods
We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm‐NPS‐DI) underlying the Nutri‐Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm‐NPS‐DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake.
Results
We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow‐up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm‐NPS‐DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24–3.36; p‐trend: <0.01). Among items of the FSAm‐NPS‐DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm‐NPS‐DI Score: aHR: 0.91, 95% CI: 0.69–1.21; p‐trend: 0.76).
Conclusions
A diet with low nutritional quality as measured by the FSAm‐NPS‐DI Score is associated with a higher risk of CD but not UC.
Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aims/hypothesis
Studies on weight cycling and the risk of type 2 diabetes have revealed inconsistent results, possibly due to differences in the definition of weight fluctuations. Here, we ...investigated whether weight cycling during adulthood is related to diabetes risk in a large cohort study, using a complementary approach to define patterns of weight development.
Methods
Weight cycling, weight loss and weight gain were defined (1) a priori, using distinct categories, and (2) by functional principal component analysis (FPCA) to capture weight patterns in greater detail. Associations of weight cycling, weight loss and weight gain with the risk of type 2 diabetes were evaluated by Cox regression models.
Results
A priori defined weight cycling was associated with increased diabetes risk, compared with stable weight (HR 1.36 95% CI 1.09, 1.68). No significant association between FPCA-derived weight cycling and risk of diabetes was observed after adjustment for concurrent weight patterns (HR 1.19 95% CI 0.89, 1.60). Subgroup analyses showed that FPCA-derived weight cycling during net weight gain was associated with a higher risk of diabetes (HR 1.68 95% CI 1.14, 2.48). A priori defined weight gain (HR 2.08 95% CI 1.60, 2.70) was more clearly related to the risk of diabetes than FPCA-derived weight gain (HR 1.20 95% CI 0.95, 1.51), while no significant associations were observed for weight loss.
Conclusions/interpretation
Overall, weight cycling may not be an independent risk factor for type 2 diabetes when accounting for concurrent patterns of weight development. However, weight cycling may pose a stronger risk of diabetes than non-cycling during net weight gain.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Scope
The goal of this work is to identify circulating biomarkers of habitual coffee intake using a metabolomic approach, and to investigate their associations with coffee intake in four European ...countries.
Methods and results
Untargeted mass spectrometry‐based metabolic profiling is performed on serum samples from 451 participants of the European Prospective Investigation on Cancer and Nutrition (EPIC) originating from France, Germany, Greece, and Italy. Eleven coffee metabolites are found to be associated with self‐reported habitual coffee intake, including eight more strongly correlated (r = 0.25–0.51, p < 10E−07). Trigonelline shows the highest correlation, followed by caffeine, two caffeine metabolites (paraxanthine and 5‐Acetylamino‐6‐amino‐3‐methyluracil), quinic acid, and three compounds derived from coffee roasting (cyclo(prolyl‐valyl), cyclo(isoleucyl‐prolyl), cyclo(leucyl‐prolyl), and pyrocatechol sulfate). Differences in the magnitude of correlations are observed between countries, with trigonelline most highly correlated with coffee intake in France and Germany, quinic acid in Greece, and cyclo(isoleucyl‐prolyl) in Italy.
Conclusion
Several biomarkers of habitual coffee intake are identified. No unique biomarker is found to be optimal for all tested populations. Instead, optimal biomarkers are shown to depend on the population and on the type of coffee consumed. These biomarkers should help to further explore the role of coffee in disease risk.
Eleven metabolites measured in serum samples from 451 subjects of the European Prospective Investigation on Cancer and Nutrition (EPIC) study originating from France, Germany, Greece and Italy were found to be associated with coffee intake. They include trigonellline, caffeine and caffeine metabolites, quinic acid, and two diketopiperazines and catechol sulfate derived from coffee roasting. Variations in the magnitude of correlations and of ratios between metabolites indicate differences in the composition of coffee brews consumed by individuals from the four countries.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Circulating oxysterols have been proposed as biological markers of disease risk. However, within-person reproducibility of circulating oxysterols over time is not well established.
We evaluated the ...one-year reproducibility of 11 oxysterols and lanosterol among 30 postmenopausal women with repeat blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) - Heidelberg, Germany cohort. Liquid chromatography–mass spectrometry (LC/MS) was performed to quantify serum concentrations of 22R–hydroxycholesterol, 25-hydroxycholesterol, 24S-hydroxycholesterol, 27-hydroxycholesterol, 22S-hydroxycholeterol, 24,25-epoxycholesterol, 5α,6β-dihydroxycholestanol, 7α-hydroxycholesterol, 5β,6β-epoxycholesterol, 5α,6α-epoxycholesterol, 24-dihydrolanosterol, and lanosterol. We evaluated Spearman correlations and intraclass correlation coefficients (ICCs) between quantifiable concentrations measured in repeat samples taken one-year apart to estimate within-person reproducibility.
Spearman correlations (ICCs) over one year ranged from 0 (ICC=0.10) for 5β,6β-epoxycholesterol and 0.10 (ICC=0.20) for 5α,6α-epoxycholesterol, representing low within-person stability, to 0.81 (ICC=0.75) for 27-hydroxycholesterol and 0.86 (ICC=0.91) for 24S–hydroxycholesterol, representing relatively high within-person stability. Correlations between oxysterols and lanosterol ranged from 0.01 between 24S-hydroxycholesterol and lanosterol to 0.70 between 5α,6α-epoxycholesterol and 5β,6β-epoxycholesterol.
Our results demonstrate that for 27-hydroxycholesterol, 24S–hydroxycholesterol, 25-hydroxycholesterol, 7α-hydroxycholesterol and lanosterol, a single serum measurement can reliably estimate average levels over a one-year period. Circulating oxysterols are of increasing interest in epidemiologic studies of chronic disease risk including cancer and cardiovascular disease. Our data suggest that within-person stability of oxysterols differs depending on the individual oxysterol evaluated. We identified four oxysterols and lanosterol as stable over time to inform the use of circulating oxysterols in epidemiologic studies.
•Four oxysterols and lanosterol demonstrated high reproducibility over one year.•5β,6β-epoxycholesterol and 5α,6α-epoxycholesterol had low reproducibility.•The studied oxysterols and lanosterol were not strongly correlated with age or BMI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Glyceraldehyde‐derived advanced glycation end products (glycer‐AGEs) could contribute to colorectal cancer development and progression due to their pro‐oxidative and pro‐inflammatory properties. ...However, the association of glycer‐AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer‐AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer‐AGEs concentrations with CRC‐specific and all‐cause mortality among 1034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow‐up, 529 participants died (409 from CRC). Glycer‐AGEs were statistically significantly positively associated with CRC‐specific (HRQ5 vs Q1 = 1.53, 95% CI: 1.04‐2.25, Ptrend = .002) and all‐cause (HRQ5 vs Q1 = 1.62, 95% CI: 1.16‐2.26, Ptrend < .001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer‐AGEs and CRC‐specific mortality among patients with distal colon cancer (per SD increment: HRproximal colon = 1.02, 95% CI: 0.74‐1.42; HRdistal colon = 1.51, 95% CI: 1.20‐1.91; Peffect modification = .02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer‐AGEs category relative to lowest BMI and glycer‐AGEs category for both CRC‐specific (HR = 1.78, 95% CI: 1.02‐3.01) and all‐cause mortality (HR = 2.15, 95% CI: 1.33‐3.47), although no statistically significant effect modification was observed. Our study found that prediagnostic circulating glycer‐AGEs are positively associated with CRC‐specific and all‐cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted.
What's new?
Eating foods high in sugar has been associated with risk of colorectal cancer (CRC). As the body processes dietary sugars, it generates compounds called glyceraldehyde‐derived advanced glycation end products (glycer‐AGEs). Here, the authors investigated the relationship between glycer‐AGEs and CRC mortality. In an analysis of 1034 CRC cases from the EPIC cohort, they found that prediagnostic circulating glycer‐AGEs were associated with both CRC‐specific and all‐cause mortality.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date.
We aimed to ...identify existing evidence for gene-macronutrient interactions and T2D and to examine the reported interactions in a large-scale study.
We systematically reviewed studies reporting gene-macronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015. Eligibility criteria included assessment of macronutrient quantity (e.g., total carbohydrate) or indicators of quality (e.g., dietary fiber) by use of self-report or objective biomarkers of intake. Interactions identified in the review were subsequently examined in the EPIC (European Prospective Investigation into Cancer)-InterAct case-cohort study (
= 21,148, with 9403 T2D cases; 8 European countries). Prentice-weighted Cox regression was used to estimate country-specific HRs, 95% CIs, and
-interaction values, which were then pooled by random-effects meta-analysis. A primary model was fitted by using the same covariates as reported in the published studies, and a second model adjusted for additional covariates and estimated the effects of isocaloric macronutrient substitution.
Thirteen observational studies met the eligibility criteria (
< 1700 cases). Eight unique interactions were reported to be significant between macronutrients carbohydrate, fat, saturated fat, dietary fiber, and glycemic load derived from self-report of dietary intake and circulating n-3 (ω-3) polyunsaturated fatty acids and genetic variants in or near transcription factor 7-like 2 (
), gastric inhibitory polypeptide receptor (
), caveolin 2 (
), and peptidase D (
) (
-interaction < 0.05). We found no evidence of interaction when we tried to replicate previously reported interactions. In addition, no interactions were detected in models with additional covariates.
Eight gene-macronutrient interactions were identified for the risk of T2D from the literature. These interactions were not replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in the original reports. Our findings highlight the importance of independent replication of reported interactions.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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