Background: Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated. Methods and findings: We measured plasma phospholipid fatty acids by gas-chromatography in 27,296 adults, including 12,132 incident cases of T2D over the follow-up period between baseline (1991-1998) to 2007 in eight European countries in EPIC-InterAct, a nested case-cohort study. Deriving the first principal component from 27 individual fatty acids (mol%) as the main exposure (subsequently described as the FA-pattern score), the FA-pattern score explained 16.1% of the overall variability of the 27 fatty acids, partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very long-chain saturated fatty acids and low concentrations of γ- linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifths of the score, the hazard ratio of incident T2D was 0.23 (95% confidence interval: 0.19-0.29) adjusted for potential confounders and 0.37 (0.27-0.50), further adjusted for cardiometabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p<0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding. Conclusions: A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.

We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.

We found no convincing evidence that the interplay of dietary and genetic factors related to body iron status associates with type 2 diabetes risk above the level expected from the sum or product of the two individual exposures.

These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

Introduction: Diet quality indexes and lifestyle indexes (which also include other lifestyle characteristics such as smoking and obesity) have recently received increased attention in disease prevention. Hypothesis: We aimed to investigate the comparative predictive performance of a comprehensive list of dietary and lifestyle indexes in relation to cardiovascular (CVD) mortality. Methods: We applied these indexes to men and women from 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study and examined their association with 10-year CVD mortality risk. We computed 10 dietary indexes and 2 diet and lifestyle indexes and calculated quartiles. Cox proportional hazard models stratified by age and study centre, adjusted for age, BMI, energy intake, smoking status, physical activity and educational level were fit to estimate Hazard Ratios (HR) and 95% CI. Harrell’s C-statistic, a discrimination measure of predictive performance, was calculated for each model. Results: After 10 years of follow up, 3761 CVD deaths were observed among 451 256 participants. All dietary indexes, except one, were significantly associated with CVD mortality with HR ranging from 0.75 to 0.84 for the fully adjusted model when comparing top vs bottom quartile (Table 1). Stronger effect size was observed for the diet and lifestyle indexes, particularly the Healthy Lifestyle Index (HLI). Discrimination of the full models was high and did not vary between scores. We found no heterogeneity in HRs across countries for most scores, except a modest heterogeneity for Mediterranean diet scores (I 2 =48%) and HLI (75%); however, heterogeneity across countries of the C-statistics was high for all scores (I 2 = 87%). Conclusion: Our results show that diet quality as a whole, or a cluster of lifestyle behaviours including diet, are consistently associated with a reduction of 10-year CVD mortality risk and that models comprising only age, sex and lifestyle risk factors could serve as predictors of CVD mortality.

These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.

Experimental and epidemiological data suggest that vitamin D play a role in pathogenesis and progression of cancer, but prospective data on head and neck cancer (HNC) and oesophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants with blood samples between 1992 and 2000. This analysis includes 497 case-control pairs of the head and neck and oesophagus, as well as 443 additional controls. Circulating 25(OH)D₃ were measured in pre-diagnostic samples and evaluated in relation to HNC and oesophagus cancer risk and post-diagnosis all-cause mortality. After controlling for risk factors, a doubling of 25(OH)D₃ was associated with 30% lower odds of HNC (OR 0.70, 95% confidence interval [95% CI] 0.56-0.88, P_trend = 0.001). Subsequent analyses by anatomical sub-site indicated clear inverse associations with risk of larynx and hypopharynx cancer combined (OR 0.55, 95CI% 0.39-0.78) and oral cavity cancer (OR 0.60, 95CI% 0.42-0.87). Low 25(OH)D₃ concentrations were also associated with higher risk of death from any cause among HNC cases. No clear association was seen with risk or survival for oesophageal cancer. Study participants with elevated circulating concentrations of 25(OH)D₃ had decreased risk of HNC, as well as improved survival following diagnosis.

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (OR_Q4-Q1 = 1.26; 95% CI 1.00-1.58; P_trend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (OR_Q4-Q1 = 1.29; 95% CI 1.02-1.62; P_trend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.

Microvascular murine endothelial cells lines transformed by middle T oncogene of polyoma virus maintain the biological characteristics of nontransformed microvascular endothelial cells (EC). By using cell lines originated from different anatomical districts (thymus, brain, heart, and skin), we demonstrated that murine granulocyte-colony-stimulating factor (G-CSF) induces proliferation of murine microvascular endothelial cells at nanomolar concentrations without any cooperation with fetal calf serum. The proliferative effect on murine cells is less than that elicited by epidermal growth factor (EGF), used as standard for this function. G-CSF also promotes the migration of tEnd.1 endothelial cell line assayed by Boyden chamber technique. The analysis of transcript for G-CSF receptor (G-CSFR) by Northern blot hybridization and by reverse-transcriptase polymerase chain reaction (RT-PCR) shows that these cell lines have specific mRNA, with the size of that present in myeloid cells. These results indicate that G-CSF operates in the microvascular endothelial cells by a mechanism related to the presence of a specific receptor.

Cryostat sections of 58 lymph nodes were immunostained with a polyclonal rabbit serum against IL-1α, and with monoclonal antibodies directed to IL-1α (Vmp18), IL-1β (Vhp20 and BRhC3), and tumor necrosis factor α (TNFα) (B154.7). Furthermore the presence of cytokine-containing cells was correlated with the expression of endothelial leukocyte adhesion molecule (ELAM-1; 29F2) and of human leukocyte antigen (HLA-DR) (OKIa-1)by endothelial cells. Cells containing IL-1 and/or TNFα were detected mainly inpathologic conditions characterized by reactive or neoplastic expansion of the lymph node paracortex. Cells positive for IL-1 were detected in 16 of 21 cases of Hodgkin's disease,in 4 of 4 cases of T-NHL, and in 5 cases of diffuse or mixed lymphadenitis. Interleukin-1α was detected in macrophages, interdigitating reticulum cells (IDRCs), endothelial cells, and neoplastic Hodgkin's and Reed-Sternberg (H-RS) cells. Cells positive for IL-1 β were much fewer and consisted mainly of macrophages. Hodgkin's Reed-Sternberg cells were negative for IL-1β even after in vitro stimulation with bacterial endotoxin. Tumor necrosis factor α (TNFα) was present in macrophages and H-RS cells. Endothelial leukocyte adhesion molecule-1 expression by endothelial venules was detected in 17 of 20 cases of Hodgkin's disease, in 2 of 4 cases of T-NHL, and in 5 of 5 cases of diffuse lymphadenitis. In these pathologic conditions, HLADR antigens also were expressed frequently by endothelial cells. Cytokine-containing cells and ELAM-1-positive high endothelial venules (HEV) were extremely rare in lymph nodes involved by follicular lymphadenitis (12 cases) or B-NHL (16 cases). In cases of reactive or neoplastic B-cell proliferations, HLA-DR-positive HEVs still were present often. Our results indicate that IL-1/TNFα production at tissue level is often associated with ELAM-1 expression by HEVs, but is less well correlated with expression of HLA-DR antigens by endothelial cells.

Unstimulated human monocytes did not express appreciable levels of cytotoxicity on normal human umbilical vein endothelial cells (EC) in a 24-48 hr TdR release assay. On activation with IFN-gamma and LPS, monocytes had appreciable cytotoxicity on EC. Monocyte cytotoxicity on EC was not dependent on the presence of contaminating lymphoid cells. Recombinant TNF, IL-1, and IL-6 as well as monocyte supernatants did not exert a cytotoxic effect on EC. Moreover, anti-TNF, anti-IL-1, and anti-IL-6 antibodies, as well as scavengers of reactive oxygen intermediates, did not affect the cytotoxicity of activated monocytes on EC. Antibodies against the beta-chain (CD18) of leukocyte integrins inhibited the adhesion and cytotoxicity of activated monocytes on EC. Pretreatment of EC with IL-1 augmented the adhesion of monocytes on EC. Normal monocytes were not cytotoxic on IL-1-pretreated EC and IL-1 treatment did not increase the susceptibility of EC to activated monocytes. Thus adhesion is necessary but not sufficient for monocyte killing of EC. Anti-alpha L (LFA-1) antibodies markedly reduced monocyte cytotoxicity on EC, although anti-alpha X (p150) antibodies had only a modest effect. Anti-alpha M (Mac-1/CR3) antibodies were intermediate inhibitors of EC killing by activated monocytes. Thus, alpha L, beta 2 (LFA-1), and, to a lesser extent, alpha M, beta 2 (Mac-1/CR3) and alpha X, beta 2 (p 150, 95) integrins are the main adhesive structures involved in the cytotoxic interaction of activated monocytes with EC. Monocyte-mediated damage of EC could play a role as a mechanism of tissue injury under conditions of local or systemic activation of mononuclear phagocytes.