Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73-1.23; Ptrend = .97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries.

PURPOSE: Previously reported associations of protein-rich foods with stroke subtypes have prompted interest in the assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study. METHODS: We analysed data from 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-h dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to the intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants. RESULTS: After a median follow-up of 12.9 years, 4295 participants had an ischaemic stroke and 1375 participants had a haemorrhagic stroke. After correction for multiple testing, a higher intake of proline (as a percent of total protein) was associated with a 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing. CONCLUSION: Higher proline intake may be associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.

Prediagnostic serum glyceraldehyde-derived advanced glycation end products and mortality among colorectal cancer patients.

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.

Dietary patterns related to biological mechanisms and survival after breast cancer diagnosis: results from a cohort study.

BACKGROUND: Inflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival. METHODS: The diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality. RESULTS: We included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR1-SD 0.92; 95%CI 0.87-0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR1-SD 1.06; 95%CI 1.00-1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality. CONCLUSIONS: Greater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors.

Changes in Lifestyle and Risk of Colorectal Cancer in the European Prospective Investigation Into Cancer and Nutrition.

INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort. METHODS: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

Factors associated with serum ferritin levels and iron excess: results from the EPIC-EurGast study.

PURPOSE: Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and its determinants in healthy European adults. METHODS: Sociodemographic, lifestyle, iron status, dietary information, and HFE genotyping were obtained from controls from the nested case-control study EPIC-EurGast study. High sensitivity C-reactive protein (hsCRP) was measured to address possible systemic inflammation. Descriptive and multivariate analyses were used to assess iron status and its determinants. RESULTS: Out of the 828 participants (median age: 58.7 years), 43% were females. Median serum ferritin and prevalence of excess iron were 143.7 µg/L and 35.2% in males, respectively, and 77 µg/L and 20% in females, both increasing with latitude across Europe. Prevalence of HFE C282Y mutation was significantly higher in Northern and Central Europe (~ 11%) than in the South (5%). Overweight/obesity, age, and daily alcohol and heme iron intake were independent determinants for iron status, with sex differences even after excluding participants with hsCRP > 5 mg/L. Obese males showed a greater consumption of alcohol, total and red meat, and heme iron, compared with those normal weight. CONCLUSION: Obesity, higher alcohol and heme iron consumption were the main risk factors for excess iron in males while only age was associated with iron overload in females. Weight control and promoting healthy lifestyle may help prevent iron overload, especially in obese people. Further research is needed to clarify determinants of excess iron in the healthy adult population, helping to reduce the associated comorbidities.

Inflammatory potential of diet and pancreatic cancer risk in the EPIC study.

PURPOSE: There is existing evidence on the potential role of chronic inflammation in the pathogenesis of pancreatic cancer (PC) and on how risk may be modulated by dietary factors. Pro-inflammatory diets are suggested to be associated with increased risk of PC but, so far, evidence remains not conclusive. We examined the association between the dietary inflammatory potential and PC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which includes 450,112 participants. METHODS: After a 14-year follow-up, a total of 1239 incident PC cases were included in this study. The inflammatory potential of the diet was estimated using an Inflammatory Score of the Diet (ISD). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between the ISD and PC were estimated using multivariable Cox regression models, adjusted for known risk factors for PC. RESULTS: Participants with higher ISDs had a higher risk of developing PCs. In the fully adjusted multivariate model, the risk of PC increased by 11% (HR 1.11, 95% CI 1.02-1.22) for 1 point each standard deviation increase in the ISD score. Neither obesity nor any other known risk factor for PC showed statistically significant interactions. CONCLUSION: To the best of our knowledge, this is the first prospective study reporting a positive relationship between the inflammatory potential of diet and PC. Since early diagnosis and treatment of pancreatic cancer might be challenging, prevention remains the major hope for reducing the burden of this disease.

Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study.

BACKGROUND: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. METHODS: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. RESULTS: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. CONCLUSIONS: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.

Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort.

PURPOSE: Acrylamide was classified as 'probably carcinogenic' to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from eight countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log2) to improve normality. Median (25th-75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively. RESULTS: The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively. CONCLUSIONS: Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort.

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors. RESULTS: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk. CONCLUSIONS: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC.