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Abstract Background The consumption of various herbal infusions was and is common in the traditional Mediterranean diet, and apparently are used in many other regions of the world outside of the Mediterranean region. The present study aimed to investigate the consumption of herbal infusions/decoctions and tea in a nationally representative sample of Greece, considering also their Planetary use. Methods 3951 adult participants of the HYDRIA Survey (2013–2014) were included from the 13 regions of Greece. The diet of participants was assessed by two 24-h dietary recalls (24-HDR) and the Food Propensity Questionnaire (FPQ). All food items were analyzed through the HYDRIA Food Composition Tables. Information on socio-demographics, lifestyle, and health characteristics during the baseline was also provided. Results 26.9% of herbal infusions and decoctions consumers are ≥ 75 years old, pensioners with a low level of education, and residents of urban areas. However, 22.2% of tea consumers belong to the 18–34-year age group, being employed with an intermediate level of education and living in an urban area. Elderly men and women use more herbal infusions/decoctions (55.4%; 40.6%) compared to tea (41.8%; 25.2%). According to FPQ, 7.1% of men and 9.7% of women use herbal infusions and decoctions four times or more per week, while 7.1 and 10.9% of men and women, respectively, consume tea at the same frequency. Green tea, mountain tea (Sideritis spp.), and black tea are reported most frequently. In addition, mountain tea (61.2%), black tea (60.3%), mixed herbal infusions/decoctions (58.4%), and sage (59.4%) are consumed mostly at breakfast, while chamomile was reported mainly at dinner or during the night (42.4%). Conclusions Based on the FPQ results, the moderate and high consumption of herbal infusions/decoctions and tea is low in Greece, especially among adults (18–64 years). Thus, our results indicate the existence of a generation gap to the attachment to the traditional Med Diet and the consumption of herbal infusions. The present study could encourage future research to focus on herbal infusions and decoctions consumption by other populations for cross-cultural comparison, as well as on emphasizing the value of consuming locally available herbs in a Planeterranean perspective. Graphical Abstract

Abstract Background Med-Index is a one-health front-of-pack (FOP) label, based on Mediterranean diet (MedDiet) principles, developed to summarize information about the nutritional properties and related-health benefits of any food as well as its sustainable production processes, and the associated food company’s social responsibility parameters in a new “Planeterranean” perspective. Thus, Med-Index can be adopted in and by any European region and authority as well as worldwide; this is achieved by consumption and cooking of locally available and sourced foods that respect MedDiet principles, both in terms of healthy nutrition and sustainable production. The huge body of scientific evidence about the health benefits of the MedDiet model and principles requires a comprehensive framework to encompass the scientific reliability and robustness of this tool. A systematic review was carried out to examine the association between human health and adherence to MedDiet patterns upon which the “Med-Index” tool was subsequently developed. Methods MEDLINE and PubMed databases were searched for eligible publications from 1990 to April 2023. Systematic literature reviews, with or without meta-analysis, of clinical trials and observational studies were screened by two independent investigators for eligibility, data extraction, and quality assessment. English language and the time interval 1990–2023 were applied. A registry code CRD42023464807 was generated on PROSPERO and approved for this search protocol. The corrected covered area (CCA), calculated to quantify the degree of overlap between reviews, gave a slight overlap (CCA = 4%). Results A total of 84 systematic reviews out of 6681 screened records were selected. Eligible reviews included studies with predominantly observational designs (61/84, 72.6%%), of which 26/61 referenced studies of mixed observational and RCT designs, while 23/84 (27.4%) were RCT-only systematic reviews. Seventy-nine different entries were identified for health outcomes, clustered into 10 macro-categories, each reporting a statistically significant association with exposure to the MedDiet. Adherence to MedDiet was found to strongly benefit age-related chronic diseases (21.5%), neurological disorders (19%), and obesity-related metabolic features (12.65), followed by CVDs (11.4%), cancer (10.1%), diabetes (7.5%), liver health (6.3%), inflammation (5%), mortality (5%), and renal health (1.2%). The quality of the studies was moderate to high. Conclusion In the context of a “Planeterranean” framework and perspective that can be adopted in any European region and worldwide, MedDiet represents a healthy and sustainable lifestyle model, able to prevent several diseases and reduce premature mortality. In addition, the availability of a FOP, such as Med-Index, might foster more conscious food choices among consumers, paying attention both to human and planetary health.

Objective When considering proposals to improve diets, it is important to understand how factors like price and income can affect saturated fat (SF) intake and demand. In this study, we examine and estimate the influence of price and income on intake across 160 countries, by age and sex, and derive sensitivity measures (price elasticities) that vary by age, sex and world region.Design We econometrically estimate intake responsiveness to income and prices across countries, accounting for differences by world region, age and sex. Intake data by age, sex and country were obtained from the 2018 Global Dietary Database. These data were then linked to global price data for select food groups from the World Bank International Comparison Programme and income data from the World Development Indicators Databank (World Bank).Results Intake differences due to price were highly significant, with a 1% increase in price associated with a lower SF intake (% energy/d) of about 4.3 percentage points. We also find significant differences across regions. In high-income countries, median (age 40) intake reductions were 1.4, 0.8 and 0.2 percentage points, given a 1% increase in the price of meat, dairy, and oils and fats, respectively. Price elasticities varied with age but not sex. Intake differences due to income were insignificant when regional binary variables were included in the analysis.Conclusion The results of this study show heterogeneous associations among prices and intake within and across countries. Policymakers should consider these heterogeneous effects as they address global nutrition and health challenges.

Dietary (food) supplements (DSs) have seen a sharp increase in use and popularity in recent years. Information on DS consumption is vital for national nutrition monitoring. The objective of this study was to investigate whether DS intake was reported in the National Nutrition Surveys (NNSs) in all European countries. NNSs reporting DS use were retrieved via literature review (i.e., PubMed, Google Scholar, Scopus), scientific and organizational publications (EFSA), or open-published government and other official reports. Included were the European NNSs referring to adults, published in English, French, or German, post-2000. Out of the 53 European countries, 30 recorded DS intake. Among them, related findings on the percentage of DS intake were published in 21 cases, 5 of them written in the local language. DS use varied by nation, with Finland and Denmark having the greatest (over 50%) and Italy having the lowest percentage (5%). In terms of comprehensive reported data on DS consumption in Europe and the investigation of the contribution of DSs to total nutrient intake, there is a need for improvement. Common DS categories should be defined upon agreement among the involved scientific parties to allow for comparable data and estimations between surveys.

(1) Background: The chicken egg is an animal product of great agronomic interest. The egg white and yolk constitute high-quality protein sources for humans with high digestibility and well-balanced amino acid profiles. Despite the egg white and yolk protein’s undisputed value, research to unravel their full proteome content and its properties is still ongoing. We aimed to exhaustively analyze the proteome of egg white and yolk by applying intrinsic proteomics and bioinformatics approaches in order to unravel the full protein potential of this landmark food. (2) Methods: A total of 45 freshly laid, unfertilized, chicken eggs were subjected to nanoLC-MS/MS Orbitrap analysis following a peptide pre-fractionation step. A comprehensive bioinformatics processing step was undertaken towards elucidating potential activities and roles of identified molecules. In parallel, the literature was mined concerning all reported egg white and yolk protein identifications. (3) Results: Our analysis revealed 371 and 428 new proteins, reported for the first time to be present in the egg white and yolk, respectively. From the bioactivity standpoint, egg white and yolk proteins showed high enrichment for antioxidant and anti-inflammatory processes, while exerting high relevance for the apoptosis and focal adhesion pathways. (4) Conclusions: Egg white and yolk proteins exert diverse and multifaceted properties. A total of 799 proteins were reported for the first time as being part of the egg and yolk. Our novel protein data enriched those already published in the literature and the first ever chicken egg white and yolk Protein Atlas, comprising 1392 protein entries, was generated. This dataset will provide a cornerstone reference for future studies involving egg proteins.

Background: Yoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC). Methods: We pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted. Results: The analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94–1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88–0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85–0.99) and 0.78 (95% CI = 0.73–0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91–1.02) for cardia, 1.03 (95% CI = 1.00–1.07) for non-cardia, 1.12 (95% CI = 1.07–1.19) for diffuse and 1.02 (95% CI = 0.97–1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women. Conclusions: We found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association.

Abstract Background Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.

Abstract Background Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. Methods In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P

In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

Abstract Background Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. Methods Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). Results Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03–1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03–1.06 and 1.04, 95% CI 1.02–1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94–0.98; 0.96, 95% CI 0.94–0.99; and 0.96, 95% CI 0.95–0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. Conclusions Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.

Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.

Abstract Background Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort. Methods Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93–1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73–0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94–1.05). Conclusions While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.

Background There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. Methods and Results We conducted a case‐cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country‐specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice‐weighted Cox regression models and pooled results using random‐effects meta‐analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88–0.99]), cheese (HR, 0.98 [95% CI, 0.96–1.00]), and fish (HR, 0.87 [95% CI, 0.75–1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02–1.12]) and butter (HR, 1.02 [95% CI, 1.00–1.04]). Conclusions This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix.

Abstract Background Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. Methods We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses’ Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. Conclusions The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.

Abstract Background Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk. Methods A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression. Results Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity. Conclusions These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

Abstract Background Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction. Methods We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women’s Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention. Results Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10− 6 for ModelER+ and 3.0 × 10− 6 for ModelGail. Conclusions Modeling heterogeneous epidemiological risk factors might yield little improvement in BC risk prediction. Nevertheless, a model specifically predictive of ER+ tumor risk could be more applicable than an omnibus model in risk assessment for chemoprevention.

Background: This study aimed to investigate the food and macronutrient intake of the population in Greece and evaluate its adherence to the Greek traditional Mediterranean diet. Methods: Adults over 18 years old (n = 4011) were included from the 2013–2014 National Health and Nutrition survey—HYDRIA. Dietary intake was collected using two 24-h recall interviews and a nonquantitative food frequency questionnaire. Macronutrient intakes were calculated using an updated version of the Greek FCT. Results: Only 28.3% of the adult population had high adherence to the Greek traditional Mediterranean diet, with a higher percentage (39.7%) observed for participants over 65 years compared to those under 65 years (25.5%). Differences in adherence to the MD were observed among the four geographical regions in Greece. Younger adults had a higher intake of meat, cereals, alcoholic and nonalcoholic beverages, and sugar products than older individuals who consumed more vegetables, fruits, legumes, dairy, fish, and lipids (mainly from olive oil). Adults do not meet the international dietary recommendations for the intake of several foods and macronutrients. Conclusions: The adult Greek population, especially younger people, has headed away from the Greek traditional Mediterranean diet. These observations indicate potential detrimental consequences in terms of morbidity and mortality.

There is a growing recognition that social support can potentially exert consistent or opposing effects in influencing health behaviours. The present paper presents a cross-sectional study, including 2,064 adults from Italy, Spain and Greece, who were participants in a multi-centre randomised controlled trial (C4H study), aiming to examine whether social support is correlated with adherence to a healthy Mediterranean diet and physical activity. Social support data were available for 1,572 participants. The majority of the sample reported emotional support availability (84·5 %), financial support availability (72·6 %) and having one or more close friends (78·2 %). Mediterranean diet adherence was significantly associated with emotional support (P = 0·009) and social network support (P = 0·021). No statistically significant associations were found between participant physical activity and the social support aspects studied. In conclusion, emotional and social network support may be associated with increased adherence to the Mediterranean diet. However, further research is needed to evaluate the role of social support in adherence to healthy Mediterranean diet.

Abstract Background Receptor activator of nuclear factor kappa-B (RANK)-signaling is involved in tumor growth and spread in experimental models. Binding of RANK ligand (RANKL) to RANK activates signaling, which is inhibited by osteoprotegerin (OPG). We have previously shown that circulating soluble RANKL (sRANKL) and OPG are associated with breast cancer risk. Here we extend these findings to provide the first data on pre-diagnosis concentrations of sRANKL and OPG and risk of breast cancer-specific and overall mortality after a breast cancer diagnosis. Methods Two thousand six pre- and postmenopausal women with incident invasive breast cancer (1620 (81%) with ER+ disease) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed-up for mortality. Pre-diagnosis concentrations of sRANKL and OPG were quantified in baseline serum samples using an enzyme-linked immunosorbent assay and electrochemiluminescent assay, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific and overall mortality were calculated using Cox proportional hazards regression models. Results Especially in women with ER+ disease, higher circulating OPG concentrations were associated with higher risk of breast cancer-specific (quintile 5 vs 1 HR 1.77 [CI 1.03, 3.04]; ptrend 0.10) and overall mortality (q5 vs 1 HR 1.39 [CI 0.94, 2.05]; ptrend 0.02). sRANKL and the sRANKL/OPG ratio were not associated with mortality following a breast cancer diagnosis. Conclusions High pre-diagnosis endogenous concentrations of OPG, the decoy receptor for RANKL, were associated with increased risk of death after a breast cancer diagnosis, especially in those with ER+ disease. These results need to be confirmed in well-characterized patient cohorts.

The chromosome 15q25.1 locus is a leading susceptibility region for lung cancer. Here, the authors interrogate three GWAS cohorts with 42,901 individuals to investigate potential pathological pathways such as gated channel activity and neuroactive ligand receptor interaction in lung cancer etiology.

Abstract Background Representative and reliable data on health and health determinants of the population and population sub-groups are needed for evidence-informed policy making; planning and evaluation of prevention programmes; and research. Health examination surveys (HESs) including questionnaires, objective health measurements and analysis of biological samples, provide information on many health indicators that are available not at all or less reliably or completely through administrative registers or health interview surveys. Methods Standardized cross-sectional HESs were already conducted in the 1980’s and 1990’s, in the framework of the WHO MONICA Project. The methodology was developed and finally, in 2010–2012, a European Health Examination Survey (EHES) Pilot Project was conducted. During this pilot phase, an EHES Coordinating Centre (EHES CC, formerly EHES Reference Centre) was established. Standardized protocols, guidelines and quality control procedures were prepared and tested in 12 countries which conducted pilot surveys, demonstrating the feasibility of standardized HES data collection in the European Union (EU). Currently, the EHES CC operates at the National Institute for Health and Welfare (THL), Finland. Its activities include maintaining and developing the standardized protocols, guidelines and training programme; maintaining the EHES network; providing professional support for countries planning and organizing their national HESs; external quality assessment for surveys organized in the EU Member States; and development of a centralized database and joint reporting system for HES data. Results An increasing number of EU Member States are conducting national HESs, demonstrating a strong need for such surveys as part of the national health monitoring systems. Standardization of the data collection is essential to ensure that HES data are comparable across countries and over time. The work of the EHES CC helps to ensure the quality and comparability of HES data across the EU. Conclusions HES data have been used for health monitoring and identifying public health problems; to develop health and prevention programmes; to support health policies and preparation of health-related legislation and regulations; and to develop clinical treatment guidelines and population reference values. HESs have also been utilized to prepare health measurement tools and diagnostic methods; in training and research and to increase health awareness among population.

Abstract Background Leukocyte telomere length (LTL) and mitochondrial genome (mtDNA) copy number and deletions have been proposed as risk markers for various cancer types, including breast cancer (BC). Methods To gain a more comprehensive picture on how these markers can modulate BC risk, alone or in conjunction, we performed simultaneous measurements of LTL and mtDNA copy number in up to 570 BC cases and 538 controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. As a first step, we measured LTL and mtDNA copy number in 96 individuals for which a blood sample had been collected twice with an interval of 15 years. Results According to the intraclass correlation (ICC), we found very good stability over the time period for both measurements, with ICCs of 0.63 for LTL and 0.60 for mtDNA copy number. In the analysis of the entire study sample, we observed that longer LTL was strongly associated with increased risk of BC (OR 2.71, 95% CI 1.58–4.65, p = 3.07 × 10− 4 for highest vs. lowest quartile; OR 3.20, 95% CI 1.57–6.55, p = 1.41 × 10− 3 as a continuous variable). We did not find any association between mtDNA copy number and BC risk; however, when considering only the functional copies, we observed an increased risk of developing estrogen receptor-positive BC (OR 2.47, 95% CI 1.05–5.80, p = 0.04 for highest vs. lowest quartile). Conclusions We observed a very good correlation between the markers over a period of 15 years. We confirm a role of LTL in BC carcinogenesis and suggest an effect of mtDNA copy number on BC risk.

The aim of this study was to evaluate the longitudinal changes in alcohol consumption (total alcohol and types of alcoholic beverages) of the Greek EPIC cohort participants (28,572) during a 17-year period (1994–2011), with alcohol information being recorded repeatedly over time. Descriptive statistics were used to show crude trends in drinking behavior. Mixed-effects models were used to study the consumption of total alcohol, wine, beer and spirits/other alcoholic beverages in relation to birth cohort, socio-demographic, lifestyle and health factors. We observed a decreasing trend of alcohol intake as age increased, consistent for total alcohol consumption and the three types of beverages. Older birth cohorts had lower initial total alcohol consumption (8 vs. 10 g/day) and steeper decline in wine, spirits/other alcoholic beverages and total alcohol consumption compared to younger cohorts. Higher education and smoking at baseline had a positive association with longitudinal total alcohol consumption, up to +30% (vs. low education) and more than +25% (vs. non-smoking) respectively, whereas female gender, obesity, history of heart attack, diabetes, peptic ulcer and high blood pressure at baseline had a negative association of −85%, −25%, −16%, −37%, −22% and −24% respectively. Alcohol consumption changed over age with different trends among the studied subgroups and types of alcohol, suggesting targeted monitoring of alcohol consumption.

The glycaemic index (GI) is a food metric that ranks the acute impact of available (digestible) carbohydrates on blood glucose. At present, few countries regulate the inclusion of GI on food labels even though the information may assist consumers to manage blood glucose levels. Australia and New Zealand regulate GI claims as nutrition content claims and also recognize the GI Foundation’s certified Low GI trademark as an endorsement. The GI Foundation of South Africa endorses foods with low, medium and high GI symbols. In Asia, Singapore’s Healthier Choice Symbol has specific provisions for low GI claims. Low GI claims are also permitted on food labels in India. In China, there are no national regulations specific to GI; however, voluntary claims are permitted. In the USA, GI claims are not specifically regulated but are permitted, as they are deemed to fall under general food-labelling provisions. In Canada and the European Union, GI claims are not legal under current food law. Inconsistences in food regulation around the world undermine consumer and health professional confidence and call for harmonization. Global provisions for GI claims/endorsements in food standard codes would be in the best interests of people with diabetes and those at risk.

Abstract Background The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths. Results Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18–2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14–1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P heterogeneity = 0.01; HR = 0.89, 0.79–0.99 for low-intermediate grade and HR = 1.32, 1.01–1.72 for high-grade prostate cancer) and stage (P heterogeneity = 0.01; HR = 0.86, 0.75–0.99 for localised stage and HR = 1.11, 0.92–1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09–1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07–1.92) and fatal prostate cancer (HR = 1.55, 1.23–1.96). Conclusions The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.

Abstract Background Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer. Methods In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure. Results Seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p

Abstract Background Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. Methods We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. Results Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70–81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. Conclusions These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.