Search

Background and Aims: The overall macronutrient composition of diet, rather than just calorie intake, may influence long-term changes of anthropometry. We investigated relationships between dietary macronutrient composition and long-term changes in weight and waist circumference in participants of the EPIC-Italy - the Italian section of the European Prospective Investigation into Cancer and Nutrition - study., Methods and Results: A total of 32,119 participants provided anthropometric measures at recruitment and 12 years later (mean). Diet at recruitment was assessed using validated semi-quantitative food frequency questionnaires. Weight and waist changes associated with replacing 10% of energy from one macronutrient with 10% of energy from another macronutrient were assessed by multivariable linear regression. Increased energy from total protein at the expense of any other macronutrient was significantly associated with increased weight and waist circumference. Increased starch at the expense of sugar and total protein was associated with significantly decreased weight and waist circumference; when starch replaced total fat, weight significantly decreased. Increased sugar at the expense of starch and total fat was significantly associated with increased weight and waist circumference; but increase at the expense of total protein was significantly associated with decreased weight and waist circumference., Conclusion: Our results suggest that increasing protein at the expense of fat or carbohydrates, and reducing starch by increasing other macronutrients, might be associated with increased weight and waist gain., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The relation of dairy product consumption to health and mortality is controversial., Objectives: We investigated associations of consumption of various dairy products with mortality in the Italian cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Italy study., Methods: Dairy product consumption was assessed by validated semiquantitative FFQs. Multivariable Cox models stratified by center, age, and sex and adjusted for confounders estimated associations of milk (total, full fat, and reduced fat), yogurt, cheese, butter, and dairy calcium consumption with mortality for cancer, cardiovascular disease, and all causes. Nonlinearity was tested by restricted cubic spline regression., Results: After a median follow-up of 14.9 y, 2468 deaths were identified in 45,009 participants: 59% from cancer and 19% from cardiovascular disease. No significant association of consumption of any dairy product with mortality was found in the fully adjusted models. A 25% reduction in risk of all-cause mortality was found for milk intake from 160 to 120 g/d (HR: 0.75; 95% CI: 0.61, 0.91) but not for the highest (>200 g/d) category of intake (HR: 0.95; 95% CI: 0.84, 1.08) compared with nonconsumption. Associations of full-fat and reduced-fat milk consumption with all-cause and cause-specific mortality were similar to those for milk as a whole., Conclusions: In this Italian cohort characterized by low to average milk consumption, we found no evidence of a dose-response association between milk consumption and mortality and also no association of consumption of other dairy products investigated with mortality., (Copyright © American Society for Nutrition 2019.)

Objectives: The effect of modifiable stroke risk factors in terms of prevented cases remains unclear due to sex-specific disease rate and risk factors prevalence. Our aim was to estimate their impact on stroke by gender through population-attributable fraction (PAF), preventive fraction (PF) and their combination in EPIC-Italian cohort., Methods: 43,976 participants, age 34-75, and free of cardiovascular disease at baseline (1993-1998) were followed up for almost 11 years. Adjusted hazard ratios and PAF were estimated using Cox models., Results: We identified 386 cases. In males, the burden for stroke was 17% (95% CI 4-28%) for smoking and 14% (95% CI 5-22%) for alcohol consumption. In females, hypertension was carrying the biggest burden with 18% (95% CI 9-26%) followed by smoking 15% (95% CI 7-22%). Their combination was 46% (95% CI 32-58%) in males and 48% (95% CI 35-59%) in females. PF for current smokers was gender unequal [males 21% (95% CI 15-27%) females 9% (95% CI 1-17%)]., Conclusions: Half of strokes are attributable to potentially modifiable factors. The proportion of prevented cases is gender unbalanced, encouraging sex-specific intervention.

Adherence to the Mediterranean diet (MD) has a preventive effect on colorectal cancer (CRC). Several biological mechanisms have been hypothesized to explain this effect, but the involvement of clinical mediators has not been experimentally proven. We examined the role of abdominal adiposity (i.e., waist-to-hip ratio, WHR) as a potential mediator of the relationship between the MD and CRC in the Italian centres of the European Prospective Investigation into Cancer and Nutrition. We evaluated the effect of the Italian Mediterranean Index (IMI) on WHR and of WHR on CRC risk. We then estimated the natural indirect effect (NIE, mediated by WHR) and the pure direct effect (PDE, unmediated) of IMI on CRC risk using mediation analyses, considering age, sex, education, physical activity, smoking and EPIC centre as confounders. Increased IMI was associated with significantly decreased odds of high WHR (odds ratio [OR] for an IMI of 6-11 vs. 0-1: 0.88, 95% confidence interval [CI]: 0.81-0.97). There was a positive relationship between WHR and CRC (hazard ratio [HR] for high vs. low WHR: 1.34, 95%CI: 1.09-1.66). The total effect of IMI was protective on CRC risk and was mainly explained by the PDE (HR for an IMI of 6-11 vs. 0-1: 0.51, 95%CI: 0.31-0.83), whereas the NIE was 1.00 (95%CI: 0.94-1.10). In this Mediterranean cohort, the protective effect of the MD on the development of CRC was not mediated by abdominal adiposity. Since this is the first study to investigate the mediating effect of abdominal obesity, other studies are needed to replicate this result., (© 2017 UICC.)

Purpose: Breast cancer (BC) is the most frequent cancer among women in developed countries. Physical activity (PA), body mass index (BMI), and alcohol intake have been identified as relevant lifestyle modifiable risk factors for post-menopausal BC. We aimed to evaluate the role of these factors in modulating post-menopausal BC risk and to estimate the proportion of BC cases attributable to low PA, high BMI, and alcohol taking into account non-modifiable factors., Methods: In the Italian section of the EPIC study, 15,010 post-menopausal women were recruited and provided information about dietary and lifestyle habits including PA, smoking, reproductive history, and anthropometric measurements. During 14.8 years of median follow-up, 672 incident BC cases (607 invasive and 65 in situ) were identified., Results: In multivariate models, inverse associations with BC risk emerged for increasing level of total (p trend 0.02), leisure time (p trend 0.04), and occupational (p trend 0.007) PA. High BMI (HR 1.21; 95% CI 1.02-1.43 and HR 1.33; 95% CI 1.06-1.65 for overweight and obesity, respectively) and alcohol consumption higher than 10 g/day (HR 1.30; 95% CI 1.09-1.54) were associated with BC risk. We estimated that 30% (95% CI 8-50%) of post-menopausal BC cases would be avoided through an increase of leisure time PA, a BMI below 25.0, and consuming no more than one drink/day., Conclusions: This large study carried out in Mediterranean women confirms the role of PA, BMI, and alcohol consumption in modulating post-menopausal BC risk and supports the potential benefits obtainable by modifying these lifestyle factors.

Background: A consistent association has been reported between low socioeconomic status (SES) and cardiovascular events (CE), whereas the association between SES and cerebrovascular events (CBVD) is less clear. The aim of this study was to investigate the association between SES (measured using education) and CE/CBVD in a cohort study, as well as to investigate lifestyle and clinical risk factors, to help to clarify the mechanisms by which SES influences CE/CBVD., Material and Methods: We searched for diagnoses of CE and CBVD in the clinical records of 47,749 members of the EPICOR cohort (average follow-up time: 11 years). SES was determined by the relative index of inequality (RII)., Results: A total of 1,156 CE and 468 CBVD were found in the clinical records. An increased risk of CE was observed in the crude Cox model for the third tertile of RII compared to the first tertile (hazard ratio [HR] = 1.39; 95% confidence interval [CI] 1.21-1.61). The increased risk persisted after adjustment for lifestyle risk factors (HR = 1.19; 95%CI 1.02-1.38), clinical risk factors (HR = 1.35; 95%CI 1.17-1.56), and after full adjustment (HR = 1.17; 95%CI 1.01-1.37). Structural equation model showed that lifestyle rather than clinical risk factors are involved in the mechanisms by which education influences CE. No significant association was found between education and CBVD. A strong relationship was observed between education and diabetes at baseline., Conclusion: The most important burden of inequality in CE incidence in Italy is due to lifestyle risk factors., Competing Interests: The authors have declared that no competing interests exist.

Background: DNA methylation profiles are responsive to environmental stimuli and metabolic shifts. This makes DNA methylation a potential biomarker of environmental-related and lifestyle-driven diseases of adulthood. Therefore, we investigated if white blood cells' (WBCs) DNA methylation profiles are associated with myocardial infarction (MI) occurrence. Whole-genome DNA methylation was investigated by microarray analysis in 292 MI cases and 292 matched controls from the large prospective Italian European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (EPICOR study). Significant signals (false discovery rate (FDR) adjusted P < 0.05) were replicated by mass spectrometry in 317 MI cases and 262 controls from the Dutch EPIC cohort (EPIC-NL). Long interspersed nuclear element-1 (LINE-1) methylation profiles were also evaluated in both groups., Results: A differentially methylated region (DMR) within the zinc finger and BTB domain-containing protein 12 (ZBTB12) gene body and LINE-1 hypomethylation were identified in EPICOR MI cases and replicated in the EPIC-NL sample (ZBTB12-DMR meta-analysis: effect size ± se = -0.016 ± 0.003, 95 % CI = -0.021;-0.011, P = 7.54 × 10(-10); LINE-1 methylation meta-analysis: effect size ± se = -0.161 ± 0.040, 95 % CI = -0.239;-0.082, P = 6.01 × 10(-5)). Moreover, cases with shorter time to disease had more pronounced ZBTB12-DMR hypomethylation (meta-analysis, men: effect size ± se = -0.0059 ± 0.0017, P TREND = 5.0 × 10(-4); women: effect size ± se = -0.0053 ± 0.0019, P TREND = 6.5 × 10(-3)) and LINE-1 hypomethylation (meta-analysis, men: effect size ± se = -0.0010 ± 0.0003, P TREND = 1.6 × 10(-3); women: effect size ± se = -0.0008 ± 0.0004, P TREND = 0.026) than MI cases with longer time to disease. In the EPIC-NL replication panel, DNA methylation profiles improved case-control discrimination and reclassification when compared with traditional MI risk factors only (net reclassification improvement (95 % CI) between 0.23 (0.02-0.43), P = 0.034, and 0.89 (0.64-1.14), P < 1 × 10(-5))., Conclusions: Our data suggest that specific methylation profiles can be detected in WBCs, in a preclinical condition, several years before the occurrence of MI, providing an independent signature of cardiovascular risk. We showed that prediction accuracy can be improved when DNA methylation is taken into account together with traditional MI risk factors, although further confirmation on a larger sample is warranted. Our findings support the potential use of DNA methylation patterns in peripheral blood white cells as promising early biomarkers of MI.

Background: Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed., Methods: We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center., Results: Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44-0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19-3.66; 3rd tertile 2.48 95%CI: 1.32-4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk., Conclusions: Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.

The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed colorectal cancer (CRC, n = 159) or breast cancer (BC, n = 166) and matched subjects who remained clinically healthy. In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, eight differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1 and miR-548a-1; all Bonferroni-adjusted P < 0.05). No significant associations were found with CRC. Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: to investigate hypothesised relationships between diet and cancer by assessing diet as a whole, in the Italian cohort EPIC., Design: multicentric prospective study., Setting and Participants: 47,749 volunteers were recruited between 1993 and 1998 in the centres of Varese and Turin (Northern Italy), Florence (Central Italy), Naples and Ragusa (Southern Italy). Information on diet and lifestyle were collected through validated questionnaires. Anthropometric measurements were taken and biological samples collected using standardised protocols., Main Outcome Measures: follow-up was carried out by accessing regional cancer and mortality registries, hospital discharge records, and by telephone inquiries (only for Naples). After a median follow-up of 11 years, 879 incident cases of breast cancer, 421 cases of colorectal cancer, and 152 deaths were identified. Multivariate Cox regression models were used to estimate risks in relation to dietary characteristics., Results: the "Olive oil & Salad" dietary pattern, characterised by high consumption of raw vegetables and olive oil, was associated with a lower risk of overall mortality in the elderly. Adherence to a Mediterranean diet rich in vegetables and fruit was associated with reduced risk of colon cancer. Consumption of high-glycemic carbohydrates was associated with higher incidence of breast cancer and colorectal cancer. Reduced risk of colon cancer was also found in regular consumers of yoghurt., Conclusions: the accuracy and comprehensiveness of EPIC-Italy data made it possible to investigate both individual dietary components and dietary habits as a whole, to thereby provide Italians with dietary and lifestyle advice that will help them to remain healthy.

Objectives: to report and evaluate the evidence produced by the EPIC Italian collaboration (EPICOR Project) on the dietary determinants of cardiovascular diseases in Italy., Design: prospective study carried out in a large Italian population, composed by cohorts recruited in Northern, Central and Southern Italy., Setting and Participants: data on dietary habits collected at the baseline observation through standardised questionnaires on 47,749 free-living adults at the time of the recruitment of the study (1993-1998)., Main Outcome Measures: major coronary and cerebrovascular events (acute coronary syndrome, PTCA, CABG, ischemic and haemorrhagic stroke, TEA of supraortic vessels) identified at follow-up. The longitudinal analyses here reported have measured risks through the use of multivariate Cox regression models, adjusted for potential confounders., Results: the longitudinal analyses of EPICOR indicate that Mediterranean-oriented dietary habits, measured through specific indicators and the consumption of various typical food, are able to reduce coronary and cerebrovascular risks, and that this protection is possible even nowadays, although many changes in diet have occurred in the last decades in Italy. Habitual consumption of plant origin products, including all foods with low glycemic index, is an advantage for cardiovascular risk., Conclusions: the EPICOR Project is the largest, long-lasting Italian study on the relationship between diet and cardiovascular diseases. It is also the study with the greater number of observed variables. Its results point out the importance to support preventive programmes and industrial policies able to favour a dietary style inspired to the Italian Mediterranean tradition.

Background: Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation., Results: In EPIC, we found that high epigenome-wide methylation was associated with lower risk of breast cancer (odds ratio (OR) per 1 SD = 0.61, 95 % confidence interval (CI) 0.47-0.80; -0.2 % average difference in epigenome-wide methylation for cases and controls). Specifically, this was observed in gene bodies (OR = 0.51, 95 % CI 0.38-0.69) but not in gene promoters (OR = 0.92, 95 % CI 0.64-1.32). The association was not replicated in NOWAC (OR = 1.03 95 % CI 0.81-1.30). The reasons for heterogeneity across studies are unclear. However, data from the BGS cohort was consistent with epigenome-wide hypomethylation in breast cancer cases across the overlapping 450k probe sites (difference in average epigenome-wide methylation in case and control DNA pools = -0.2 %)., Conclusions: We conclude that epigenome-wide hypomethylation of DNA from pre-diagnostic blood samples may be predictive of breast cancer risk and may thus be useful as a clinical biomarker.

Background: Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as a risk factor for breast cancer; however few studies - most confined to postmenopausal women - have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women., Methods: We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models., Results: Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004)., Conclusions: These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of metabolic syndrome through lifestyle changes could confer protection against breast cancer.

Aim: Our study aim was to investigate the degree of adherence to international recommendations for cutaneous melanoma pathology reports at the population level by a EUROCARE high resolution study., Methods: The availability of nine characteristics - predominant cell type, tumour-infiltrating lymphocytes, mitotic index, histological subtype, growth phase, Clark level, Breslow thickness, ulceration, and sentinel-node biopsy - was examined on pathology reports of a random sample of 636 cases diagnosed in 2003-2005 in seven Italian cancer registries: Biella, Ferrara, Firenze, Latina, Ragusa, Reggio Emilia, Romagna. The odds of having (versus not having) information for all four core characteristics (last four listed above) were estimated., Results: Sentinel node biopsy was available most often, followed by Clark level, Breslow thickness, histological subtype and ulceration. Information on all nine characteristics was more often available in Biella and Ferrara (northern Italy) than elsewhere. Information on all four core items was available for 78% of cases. Odds of four-core-item availability were higher (than mean) in Biella and lower in Latina (centre) and Ragusa (south)., Conclusions: The availability of information important for staging and management was good overall on pathology reports, but varied with geography. It is likely to be improved by wider dissemination of reporting guidelines and adoption of a standardised synoptic reporting system., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Purpose: Tissue factor (TF) expression is increased in inflammatory atherosclerotic plaques and has been related to their thrombogenicity. Blood-borne TF has been also demonstrated to contribute to thrombogenesis. However, few studies have evaluated the association of circulating levels of TF with stroke. We investigated the association of baseline circulating levels of TF with stroke events occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort., Methods: Using a nested case-cohort design, a center-stratified random sample of 839 subjects (66% women; age range, 35-71 years) was selected as subcohort and compared with 292 strokes in a mean follow-up of 9 years. Blood samples were collected at baseline in citrate, plasma was stored in liquid nitrogen and TF was measured by ELISA (IMUBIND, TF ELISA, Instrumentation Laboratory, Milan, Italy). The odd ratios and 95% confidence intervals, adjusted by relevant confounders (covariates of TF) and stratified by center, were estimated by a Cox regression model using Prentice method., Results: Individuals in the highest compared with the lowest quartile of TF plasma levels had significantly increased risk of stroke (odds ratioIVvsI quartile, 2.01; 95% confidence interval, 1.25-3.23). The association was independent from several potential confounders (odds ratioIVvsI quartile, 1.91; 95% confidence interval, 1.15-3.19). No differences were observed between men and women. The increase in risk was restricted to ischemic strokes (odds ratioIVvsI quartile, 2.13; 95% confidence interval, 1.10-4.12; fully adjusted model), whereas high levels of TF were not associated with the risk of hemorrhagic stroke (odds ratioIVvsI quartile, 1.12; 95% confidence interval, 0.49-2.55; fully adjusted model)., Conclusions: Our data provide evidence that elevated levels of circulating TF are potential risk factors for ischemic strokes., (© 2015 American Heart Association, Inc.)

Background: The relationship between coffee consumption and coronary heart disease (CHD) has been investigated in several studies with discrepant results. We examined the association between Italian-style (espresso and mocha) coffee consumption and CHD risk., Methods: We investigated 12,800 men and 30,449 women without history of cardiovascular disease recruited to the EPICOR prospective cohort study. Coffee consumption was assessed at baseline. In a random sub-cohort of 1472 subjects, plasma triglycerides, and total, LDL and HDL cholesterol were determined to investigate the effect of coffee consumption on plasma lipids., Results: After a mean follow up of 10.9 years, 804 cases of CHD (500 acute events, 56 fatal events and 248 revascularizations, all first events) were identified. Multivariable adjusted hazard ratios for CHD were: 1.18 (95% CI 0.87-1.60) for drinking 1-2 cups/day, 1.37 (95% CI 1.03-1.82) for >2-4 cups/day and 1.52 (95% CI 1.11-2.07) for over 4 cups/day (P trend <0.001) compared to reference (<1 cup/day). Plasma triglycerides, and total, LDL and HDL cholesterol did not vary significantly (ANOVA) with coffee consumption., Conclusion: Consumption of over 2 cups/day of Italian-style coffee is associated with increased CHD risk, but coffee consumption was not associated with plasma lipid changes, so the adverse effect of consumption appears unrelated to lipid profile.

Stroke is a major cause of death. Several foods and nutrients have been linked to stroke, but their effects may be best investigated considering the entire diet. In the present EPICOR study, we investigated the association between stroke and adherence to 4 a priori-defined dietary patterns: Healthy Eating Index 2005 (HEI-2005), Dietary Approaches to Stop Hypertension (DASH), Greek Mediterranean Index, and Italian Mediterranean Index. We followed 40,681 volunteers and estimated the HR and 95%CI for stroke according to dietary pattern by using multivariate Cox models with adjustment for risk factors. During a mean follow-up of 7.9 y, 178 stroke cases were diagnosed (100 ischemic, 47 hemorrhagic). Scores of 3 dietary patterns (not HEI) were inversely associated with risk of all types of stroke, with the strongest association for the Italian Index [HR = 0.47 (95%CI = 0.30-0.75); third vs. first tertile]. All patterns were significantly inversely associated with ischemic stroke except the Greek Index, with the strongest association for the Italian Index [HR = 0.37 (95%CI = 0.19-0.70); third vs. first tertile]. Only the Italian Index tended to be inversely associated with hemorrhagic stroke [HR = 0.51 (95%CI = 0.22-1.20); P = 0.07)]. These epidemiological findings suggest that adherence to any one dietary pattern investigated would protect against at least one type of stroke. For our Italian population, a diet with a high score on the Italian Index was associated with the greatest risk reduction, probably because it was conceived to capture healthy eating in the context of foods typically available in Italy.

Background: Many observational studies support the recommendation to eat sufficient amounts of fruit and vegetables as part of a healthy diet., Objective: The present study aimed to investigate the association between consumption of fruit, vegetables, and olive oil and the incidence of coronary heart disease (CHD) in 29,689 women enrolled between 1993 and 1998 in 5 European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts in northern (Turin and Varese), central (Florence), and southern (Naples and Ragusa) Italy., Design: Baseline dietary, anthropometric, and lifestyle characteristics were collected. Major events of CHD (fatal and nonfatal myocardial infarction and coronary revascularization) were identified through a review of clinical records. Analyses were stratified by center and adjusted for hypertension, smoking, education, menopause, physical activity, anthropometric measures, nonalcohol energy, alcohol, total meat, vegetables in analyses for fruit, and fruit in analyses for vegetables., Results: During a mean follow-up of 7.85 y, 144 major CHD events were identified. A strong reduction in CHD risk among women in the highest quartile of consumption of leafy vegetables (hazard ratio: 0.54; 95% CI: 0.33, 0.90; P for trend = 0.03) and olive oil (hazard ratio: 0.56; 95% CI: 0.31, 0.99; P for trend = 0.04) was found. In contrast, no association emerged between fruit consumption and CHD risk., Conclusion: An inverse association between increasing consumption of leafy vegetables and olive oil and CHD risk emerged in this large cohort of Italian women.

Introduction: Hip fractures constitute a major and growing public health problem amongst the elderly worldwide. We examined the association of anthropometry and physical activity with hip fracture incidence in a cohort of elderly Europeans, participants in the European Prospective Investigation into Cancer and nutrition (EPIC) study., Materials and Methods: The study population consisted of 27 982 volunteers (10 553 men and 17 429 women) aged 60 years and above from five European countries. Information on anthropometry, physical activity, medical history and other characteristics was collected at baseline. During a median follow-up of 8 years, 261 incident hip fractures (203 women and 58 men) were recorded. Data were analysed through Cox proportional hazard regression with adjustment for potential confounders., Results: A higher body mass index (BMI) was associated with lower hip fracture risk (hazard ratio (HR)per increasing sex-specific-quintile: 0.85, 95% confidence interval (95% CI): 0.77–0.94). Body height was associated with increased hip fracture risk (HR per 5 cm: 1.13, 95% CI: 1.01–1.25). Waist-to-hip ratio was not related to hip fracture risk. Increasing levels of leisure-time physical activity were related to lower risk (HR per increasing tertile: 0.84, 95% CI: 0.70–0.99, p for trend: 0.039)., Conclusions: In a prospective cohort study of elderly Europeans, we found evidence that high body stature increased and high BMI decreased the incidence of hip fractures. After adjustment for BMI,waist to-hip ratio was not associated with hip fracture risk. Leisure-time physical activity appears to play a beneficial role in the prevention of hip fractures., (2010 Elsevier Ltd. All rights reserved.)

Hepatitis C virus (HCV) and Epstein-Barr virus (EBV) have been repeatedly associated with risk of non-Hodgkin's lymphoma (NHL) in studies focusing on serological evidence of infection. We investigated NHL risk in association with detection of HCV-RNA or EBV-DNA in the peripheral blood mononuclear cells (PBMC). The study involved 91 NHL cases and 182 controls nested in the Italian branch of the EPIC (European Prospective Investigation of Cancer and nutrition) cohort, which obtained blood samples from 47,749 healthy volunteers between 1993 and 1998 in 5 Italian cities. NHL cases were identified until June 2005 through linkage with records of the Cancer, Mortality, and Hospital Discharge Registries. For all study subjects, we performed viral genome analyses on DNA and RNA extracted from buffy-coats and analysed EBV and HCV antibodies. The odds ratios (ORs) of NHL were 1.2 (95% confidence intervals: 0.4-3.8; 5 exposed cases) for PBMC HCV infection and 1.2 (0.7-2.3; 24 exposed cases) for PBMC EBV infection. Similar OR estimates were found for detection of EBV and HCV antibodies. These null results, although based on a relatively small sample size, suggest that persistent EBV and HCV infection in the PBMC is not a stronger predictor of NHL risk than serological evidence of infection., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Dietary glycemic load (GL) and glycemic index (GI) in relation to cardiovascular disease have been investigated in a few prospective studies with inconsistent results, particularly in men. The present EPICOR study investigated the association of GI and GL with coronary heart disease (CHD) in a large and heterogeneous cohort of Italian men and women originally recruited to the European Prospective Investigation into Cancer and Nutrition study., Methods: We studied 47 749 volunteers (15 171 men and 32 578 women) who completed a dietary questionnaire. Multivariate Cox proportional hazards modeling estimated adjusted relative risks (RRs) of CHD and 95% confidence intervals (CIs)., Results: During a median of 7.9 years of follow-up, 463 CHD cases (158 women and 305 men) were identified. Women in the highest carbohydrate intake quartile had a significantly greater risk of CHD than did those in the lowest quartile (RR, 2.00; 95% CI, 1.16-3.43), with no association found in men (P = .04 for interaction). Increasing carbohydrate intake from high-GI foods was also significantly associated with greater risk of CHD in women (RR, 1.68; 95% CI, 1.02-2.75), whereas increasing the intake of low-GI carbohydrates was not. Women in the highest GL quartile had a significantly greater risk of CHD than did those in the lowest quartile (RR, 2.24; 95% CI, 1.26-3.98), with no significant association in men (P = .03 for interaction)., Conclusion: In this Italian cohort, high dietary GL and carbohydrate intake from high-GI foods increase the overall risk of CHD in women but not men.

Introduction: Epidemiological studies have shown that dietary behaviour is an important aetiological factor in various chronic diseases. We used principal component factor analysis to identify dietary patterns and to examine the associations of these patterns with health-related variables in a sample of elderly (> or =60 years) Italians participating in the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods and Results: Exploratory factor analysis was applied to the intake of food groups as estimated by semi-quantitative food questionnaires. Individual participants were assigned factor scores, indicating the extent to which their diet conformed to each of the four dietary patterns identified: prudent (cooked vegetables, pulses, cabbage, seed oil and fish); pasta & meat (pasta, tomato sauce, red meat, processed meat, bread and wine); olive oil & salad (raw vegetables, olive oil, soup and chicken); and sweet & dairy (sugar, cakes, ice cream, coffee and dairy). Highly educated people had high scores on prudent and low scores on pasta & meat. The pasta & meat and prudent patterns were strongly positively associated with body mass index (BMI) and waist-to-hip ratio (WHR) in men and women. Hyperlipidaemic men and women consumed more of the prudent and olive oil & salad patterns and less of the sweet & dairy pattern than those with normal lipids. The olive oil & salad was significantly higher and the pasta & meat and sweet & dairy patterns significantly lower in men and women who had dieted over the previous year, suggesting awareness of the health consequences of these patterns., Conclusions: Dietary pattern analysis provides a characterization of recurrent dietary behaviour in elderly people, and can be used to provide tangible dietary advice to elderly people.

Epidemiological studies have demonstrated that many antioxidants and the total antioxidant capacity (TAC) of the diet may protect against cancers and cardiovascular disease. Common fruits and vegetables are good sources of antioxidants, although in some Mediterranean areas traditional wild greens are responsible for a significant percentage of total dietary antioxidant intake. In the European Prospective Investigation into Cancer and Nutrition cohort of Ragusa (Sicily), a high number of subjects were found to frequently eat wild greens, including Sinapis incana and Sinapis nigra, Diplotaxis erucoides, Cichorium intybus, Asparagus acutifolius, and Borrago officinalis. On the basis of these observations, detailed characterization of single antioxidant components (i.e., polyphenols, carotenoids, chlorophylls, and ascorbic acid) and the TAC of these edible wild traditional plants was performed. The wild plants examined were found to be very rich in antioxidants, such as flavonoids and carotenoids, with high TAC values, suggesting that the importance of these vegetables, not only in the traditional but even in the contemporary diet, needs to be emphasized.

The determination of pesticide metabolites in human biological fluids represents an important biomarker of exposure in the general population and exposed workers. In the frame of a prospective study, we measured the 24-h urinary excretion of 10 pesticide metabolites to evaluate non-occupational exposure to pesticides in the general population in two different areas in Italy. We collected 24-h urine samples from 69 healthy adults residing in Florence (Central Italy, n = 51) and Ragusa (Southern Italy, n = 18). The volunteers (25 males, 44 females; mean age 56 years) did not report any occupational exposure. We measured: six alkylphosphates, aspecific metabolites of organophosphorus pesticides [dimethylphosfate (DMP), dimethylthiophosfate (DMTP), dimethyldithiophosfate (DMDTP), diethylphosfate (DEP), diethylthiophosfate (DEDP), and diethyldithiophosfate (DEDTP)]; 3,5,6-trichloro-2-pyridinol (TCP), the main metabolite of chlorpyrifos; 3-phenoxybenzoic acid (3-PBA), a metabolite of pyrethroid insecticides; ethylenethiourea (ETU) a metabolite of ethylenebisdithiocarbamates; methamidophos (METH), an organophosphorus insecticide. We also measured PABA excretion as compliance marker (mean recovery 95%). Dimethylphosphates were found in detectable concentrations in the majority of samples (89.9%, 82.6% and 60.9% for DMP, DMTP and DMDTP, respectively). Urinary diethylphosphates (DEP, DETP, DEDTP) concentrations were above the detection limit in 80.9%, 61.8% and 27.5% of samples, respectively. TCP, 3-PBA and ETU were detected in 78.3%, 53.6% and 21.7% of samples, respectively. Methamidophos was detected in two samples (2.8%). The median number of metabolites detected in the same urine sample was 6 (range 0-9). Excretion levels were highest for alkylphosphates, particularly for DMTP (median: 142.6 nmol/day). Multivariate analysis showed statistically significant differences between these two groups of adults, with higher mean values of urinary excretion of alkylphosphates, TCP and ETU in Florence in comparison to Ragusa. Overall, a very high percentage of 24-h urine samples positive for several pesticide metabolites emerged, with higher levels of urinary daily excretion in subjects residing in the more urbanised area. Our results suggest that food monitoring programs should be supported by general campaigns aimed to reduce the use of pesticides in agriculture.

Background: EPIC-Italy cohort study recruited subjects who voluntarily accepted to participate in the project. From the self-selected bases of the population sample, some bias could derive in the data interpretation when risk estimation for cancer disease related to life-style factors is the principal concern. Knowledge of the bias related to self-selected sampling is important for better directing the interpretation of the EPIC-Italy study results., Methods: We investigated the characteristics of volunteer subjects recruited in the EPIC-Italy cohorts and compared them with those of the randomly selected subjects recruited in the Multipurpose ISTAT Surveys realized in the same period (1993-1998) in which the EPIC-cohorts were recruited., Results: We found some differences, and in particular a different attitude towards cigarettes smoking and wine consumption, between the EPIC cohort and the Multipurpose ISTAT Surveys, as well as among geographical areas within the EPIC cohort., Conclusions: The uneven distribution of some characteristics suggests that the self-selected subjects were characterized by an overall lower consumption of wine and cigarette smoking even when the educational level was considered. This could suggest a generally more healthy life-style among subjects recruited on a volountary bases.

One of the aims of the EPIC study is to produce accurate descriptions of the dietary habits of the participants recruited in the 27 EPIC centers of 10 European countries. To do this, different dietary assessment instruments were developed and applied to capture the wide range of diets characterizing the different European populations. Three different food frequency questionnaires were developed for Italy: one for the centers of Varese, Turin and Florence, one for Ragusa and one for Naples. These inquired about eating habits over the previous year and were completed by 46,839 Italian EPIC participants. Specially developed software analyzed the responses and linked them to food composition tables in order to provide a nutritional breakdown of individual and collective diets. A further aim of EPIC was to develop a method of rendering data from different dietary questionnaires comparable. To do this, dietary data were collected from a sample of about 8% of the Italian EPIC cohort, using a standardized computer-driven 24-hour dietary recall interview, and then compared with the dietary data collected by the questionnaires. This paper provides an extensive description of the technical features and performance of the food frequency questionnaires and the 24-hour recall interview, including a comparison of estimates of the intake of different food groups provided by the two instruments. From this comparison, the repeatability and reliability of consumption estimates was assessed, resulting in indications for improving data comparability. The paper also presents food frequency questionnaire estimates of the daily intake of foods and nutrients by center, sex and age group, as well as information on dietary habits such as place and time of intake, and food preparation and preservation methods as provided by the 24-hour recall interview. The picture that emerged is that Italian eating habits are undergoing marked changes, with a tendency to less healthy eating. Documentation of these changes in relation to age, sex and region provides an essential starting point for investigating the influence of diet on the development of cancer and other chronic diseases.

EPIC-Italy is the Italian section of a larger project known as EPIC (European Prospective Investigation into Cancer and Nutrition), a prospective study on diet and cancer carried out in 10 European countries. In the period 1993-1998, EPIC-Italy completed the recruitment of 47,749 volunteers (15,171 men, 32,578 women, aged 35-65 years) in 4 different areas covered by cancer registries: Varese (12,083 volunteers) and Turin (10,604) in the Northern part of the country; Florence (13,597) and Ragusa (6,403) in Central and Southern Italy, respectively. An associate center in Naples enrolled 5,062 women. Detailed information for each individual volunteer about diet and life-style habits, anthropometric measurements and a blood sample was collected, after signing an informed consent form. A food frequency questionnaire specifically developed for the Italian dietary pattern was tested in a pilot phase. A computerized data base with the dietary and life-style information of each participant was completed. Blood samples were processed in the same day of collection, aliquoted (RBC, WBC, serum and plasma) and stored in liquid nitrogen containers. Follow-up procedures were validated and implemented for the identification of newly diagnosed cancer cases. Cancer incidence was related to dietary habits and biochemical markers of food consumption and individual susceptibility in order to test the role of diet-related exposure in the etiology of cancer and its interaction with other environmental or genetic determinants. The comparability of information in a prospective study design is much higher than in other studies. The availability of such a large biological bank linked to individual data on dietary and life-style exposures also provides the unique opportunity of evaluating the role of selected genotypes involved in the metabolism of chemical compounds and DNA repair, potentially related to the risk of cancer, in residents of geographic areas of Italy characterized by specific cancer risk and different dietary patterns. Baseline characteristics of participants are briefly described.

The European Prospective Investigation into Cancer and nutrition offers the opportunity to explore patterns of physical activity in a large series of healthy adults enrolled in the different local cohorts of the Italian section of the European EPIC project. Physical activity is considered one of the means by which chronic disease could be prevented. Subjects in the EPIC study completed a life-style questionnaire, with a section dedicated to the assessment of physical activity at work and during leisure time. Time spent in the various activities was transformed into an index of physical activity (physical activity level, PAL) and an activity index that includes intense activity (PAL; intense activity included). Quintiles of these indexes were computed in order to observe the distribution of subject characteristics according to levels of physical activity. In general, the population was characterized by low levels of physical activity at work, with more than 50% of the sample reporting sedentary occupations. During leisure time, only a small percentage of subjects compensated for the inactivity at work by engaging in energy-consuming activities. In particular, organized fitness activities were reported by a small percentage of people, whereas walking was the most common sort of physical activity. Specific types of activity seemed to characterize subjects in the different areas of the country, reflecting local traditions or specific living situations. Detailed information about physical activity habits, together with a description of other characteristics, could help in designing physical activity promotion programs in different Italian populations and age groups.

Aims and Background: The objectives of the present study were to validate the social stratification variables adopted by the European Prospective Investigation into Cancer and Nutrition (EPIC) by comparing them with data from another independent source and to evaluate the geographic and social distribution of eating habits in the Italian EPIC population., Methods: The validation of the socioeconomic data collected by the EPIC study was performed with the Turin Longitudinal Study as gold standard and using Cohen's kappa statistics to evaluate the concordance between the studies. We then analyzed food groups based on the consumption of meat and fats, carbohydrates, sweets and alcohol, and on an index of the Mediterranean diet. The standardized scores for each food group were subdivided into quartiles, which were used to compare persons in the extreme quartiles. Analysis of the differences in eating habits by center and by educational level was conducted separately for men and women, calculating the prevalence rate ratios and controlling for age, area of birth and body mass index., Results: Concordance between the two data sources was high for educational level and low for the social-class index based on occupation. Most of the eating habits considered to be potentially harmful (high consumption of meat or fats and alcohol and low consumption of olive oil and fish) were more frequent in Northern than in Southern Italy. These habits were inversely correlated with educational level, especially in the South., Conclusions: A significant improvement in health could be obtained in the Italian population if culturally and socioeconomically disadvantaged individuals were to abandon their diet rich in meat and fats, as done by more advantaged persons. In the absence of preventive interventions specifically addressed to disadvantaged groups, it is likely that social inequalities in mortality and morbidity will increase.

Aims and Background: Several chemical compounds included in the group of polycyclic aromatic hydrocarbons (PAH) and benzene are well-known human carcinogens present in the atmosphere of polluted urban areas. Major sources include vehicle traffic and industrial emissions, but also cigarette smoke. Genotoxic damage derived from exposure to PAHs can be measured in healthy adults by specific assays as PAH-DNA adducts. In the frame of EPIC-Italy, we recently carried out a cross-sectional study in different areas of the country (Palli et al., Int J Cancer, 87: 444-451, 2000) and showed that mean DNA adduct levels varied considerably among different centers, being highest in Florence (a large metropolitan area in Tuscany) and lowest in Ragusa (a small town in Sicily)., Methods: A subgroup of EPIC volunteers, representative of these two local cohorts, agreed to collect 24-h urine samples, and we measured the excretion of two potential biomarkers of exposure to environmental pollutants: t,t-muconic acid (MA), a metabolite of benzene, and 1-hydroxypyrene (1-OHP), a metabolite of pyrene. Overall, 69 24-h urine samples were available for analyses., Results: The absolute amounts of 1-OHP and MA excreted in the 24-h urine samples were 169.6 ng and 33.8 microg, respectively. Urinary excretion of both metabolites did not vary according to age or area of residence. Strongly significant differences emerged when current smokers were compared to non-smokers for 1-OHP (P = 0.0001) and MA (P = 0.01), thus confirming that smokers are directly exposed to PAHs and benzene from tobacco smoke, with a dose-dependent effect particularly evident for MA. Multivariate analyses showed positive associations of 1-OHP excretion with male sex, low education and being overweight but not with residence in two areas with contrasting levels of urban pollution; MA excretion tended to be higher in Florence., Conclusions: These two urinary metabolites are strongly related to tobacco smoke and do not appear to represent reliable biomarkers of exposure to environmental pollutants in the general population.

A descriptive analysis was performed in order to evaluate the completeness of follow-up and to explore the occurrence of malignancy in the Italian section of the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy) at the first follow-up for cancer incidence. The EPIC-Italy cohort consisted of 47,749 subjects, aged 35-65 years, who voluntarily accepted to participate in the project from 1992-1997. Tabulations of the enrolled subjects are presented by sex, age groups, population at risk and person-years as calculated at the first follow-up in 1998; alive, lost to follow-up and dead subjects were tabulated by sex and centers. Cancer occurrence is described by quality indexes of data collected and the lapse of time between the date of recruitment and date of diagnosis. External comparisons for each center and pooled data were carried out by calculation of standard incidence ratios (SIRs) using the rates of the population-based cancer registries covering the areas of EPIC Italian centers. Similarly, an internal comparison was also performed using as the reference population the EPIC-Italy center with the lowest crude cancer incidence rates. A total of 148,968 person-years (43,568 men and 105,400 women) was calculated as the denominator; the percentages of lost to follow-up were 1.34% for men and 0.9% for women. We found 781 malignancies (216 in males and 565 in females), 17 in situ breast cancers and 8 in situ cervical cancers. In men 65 malignant cases (30.1%) and in women 186 malignancies (32.9%) occurred in the first year following enrollment. The proportion of microscopically verified cancers was 93.1%. In pooled data for men, statistically significant SIRs of less than 1 were calculated for all cancer sites combined (SIR = 0.81), lung (SIR = 0.49) and bladder (SIR = 0.62), whereas statistically significant excesses of observed cases were found for melanoma and cancers of ill-defined sites within respiratory system and intrathoracic organs (ICD-0-2 = C39). In pooled data for women, none of the SIRs were statistically significant. For men, SIRs disaggregated by center showed statistically significant excesses of cases only in Florence for the thyroid (SIR = 5.01). For women, statistically significant excesses of observed cases were computed in Florence and Varese for breast cancer (SIRs, 1.36 and 1.27, respectively), Florence for uterine cancer NOS (SIR = 20.3) and Varese for kidney (SIR 2.24). Internal comparisons showed some evidence of an excess of cases in northern compared to southern centers. In conclusion, after an average follow-up of 3 years, nearly 99% of the enrolled individuals were traced and checked for their vital status. Cancer occurrence in women was not far from that expected in comparison to the local general population, whereas in men significantly fewer cases than expected were observed. This preliminary descriptive analysis will be used as a starting point for monitoring the validity of EPIC-Italy over time.