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Background/aim: As of 2024, anal cancer (AC) has been steadily increasing worldwide but, due to insufficient evidence, anal cancer screening (ACS) has yet to be standardized. Furthermore, most high-risk people in the world have no help paying for it. Therefore, our primary endpoint was to assess the best screening method for these subjects through a provision that was free of charge (all costs were covered by the Italian public health service). Awareness-raising campaign, determination of risk factors, education on anal self-examination, and sampling (ASS) were secondary objectives., Patients and Methods: Screening was on a voluntary basis. Engaging in receptive anal intercourse and having a history of cervical dysplasia were the main inclusion criteria. Level 1 ACS tools included digital ano-rectal examination, anoscopy, anal Pap, and anal human papillomavirus (HPV) DNA test (both through self- and proctologist- sampling); high-resolution anoscopy (HRA) with (HRAB) or without biopsy comprised level 2 screening. High-risk people were enrolled until the available funds were exhausted., Results: Fifty high-risk people (40 men who had sex with men -MSM-, 9 women, and 1 heterosexual man) were enrolled. AC was found in one HIV-seropositive MSM, high-grade squamous intraepithelial lesion in 10 (20%) MSM, low-grade squamous intraepithelial lesion LSIL in 13 cases (12 MSM and 1 woman). The combination of HRAB and Pap smear screening achieved the highest values for sensitivity, specificity, and accuracy. ASS HPV DNA test provided excellent results comparable to clinician retrieval. Overweight and college education were identified as independent factors for the risk of and prevention of AC, respectively., Conclusion: A free ACS not only appears justified but also recommended to people screened for AC. Excess weight represents a further risk for this population., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: to provide evidence on how diet can influence health, greenhouse gas (GHG) emissions, and land use., Design: cohort study., Setting and Participants: data collected in the EPIC Italy cohort (N. 47,749)., Main Outcome Measures: hazard ratios (HR) for overall mortality and for cancer incidence in association with a sustainable diet (EAT-Lancet)., Results: sustainable diets are characterized by lower associated GHG emissions and lower land use (LU). Adherence to the guidelines proposed by the EAT-Lancet Commission was considered. This diet was associated with lower HRs for mortality and cancer incidence in EPIC Italy, estimated with Cox models accounting for potential confounders and stratified by sex. The hazard ratios for overall mortality showed a dose-response relationship with quartiles of diets associated with high GHG emissions, land use, and high distance from the EAT-Lancet diet calculated using a novel index, the EAT-Lancet distance index (EatDI). The HR for overall cancer incidence was also higher in the population with non-sustainable diets., Conclusions: the association among dietary GHG emissions, LU, and EatDI and overall mortality and overall cancer incidence suggests that promoting diets with low associated environmental impact can be an effective mitigation strategy with important co-benefits.

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.)

Aim: Inflammation represents a potential pathway through which socioeconomic position (SEP) is biologically embedded. Materials & methods: We analyzed inflammatory biomarkers in response to life course SEP by integrating multi-omics DNA-methylation, gene expression and protein level in 178 European Prospective Investigation into Cancer and Nutrition-Italy participants. Results & conclusion: We identified 61 potential cis acting CpG loci whose methylation levels were associated with gene expression at a Bonferroni correction. We examined the relationships between life course SEP and these 61 cis -acting regulatory methylation sites individually and jointly using several scores. Less-advantaged SEP participants exhibit, later in life, a lower inflammatory methylome score, suggesting an overall increased expression of the corresponding inflammatory genes or proteins, supporting the hypothesis that SEP impacts adult physiology through inflammation.

Objective: Colorectal cancer (CRC) is one of the most diagnosed malignant cancers worldwide. Rectal cancers (Rcs) represent one-third of all CRCs. Cigarette smoking and alcohol drinking are two underestimated risk factors for RC. We aimed to evaluate the role of alcohol consumption and cigarette smoking in modulating RC risk and to estimate the attributable fraction in a Mediterranean population., Methods: In the Italian section of the European Prospective Investigation into Cancer and Nutrition, 45,553 healthy adults (31,252 women) were recruited and provided information about lifestyle and dietary habits. During 14.0 years of median follow-up, 154 incident RC cases were identified., Results: In multivariate models, a increase in RC risk emerged among subjects drinking more than 3 drinks/day, overall (hazard ratio [HR] = 1.74; 95% confidence interval [CI] 1.08-2.80), and in females (HR= 2.80; 95% CI 1.23-6.35), compared with drinkers of less than 1 drink/day. A increase in risk also emerged for current- compared with never-smokers, overall (HR = 1.57; 95% CI 1.06-2.35; P for trend 0.03) and among males (HR = 2.04; 95% CI 1.02-4.07; P for trend 0.045). Overall, 9% (95% CI 4-14%) of RC cases were attributable to drinking more than 3 drinks/day and 12% (95% CI 3-19%) were attributable to current smoke and 20% (95% CI 11-27%) of RC cases were attributable to the independent effects of these two exposures., Conclusion: Our study supports a strategy to avoid a relevant proportion of rectal cancer cases through a combined reduction of alcohol consumption and cigarette smoking.

Background: Area deprivation index (ADI) associates with prognosis in non-dialysis CKD. However, no study has evaluated this association in CKD patients under unrestricted nephrology care., Methods: We performed a long-term prospective study to assess the role of deprivation in CKD progression and mortality in stage 1-4 CKD patients under regular nephrology care, living in Naples (Italy). We used ADI calculated at census block levels, standardized to mean values of whole population in Naples, and linked to patients by georeference method. After 12 months of "goal-oriented" nephrology treatment, we compared the risk of death or composite renal outcomes (end-stage kidney disease or doubling of serum creatinine) in the tertiles of standardized ADI. Estimated glomerular filtration rate (eGFR) decline was evaluated by mixed effects model for repeated eGFR measurements., Results: We enrolled 715 consecutive patients (age: 64 ± 15 years; 59.1% males; eGFR: 49 ± 22 mL/min/1.73 m2). Most (75.2%) were at the lowest national ADI quintile. At referral, demographic, clinical, and therapeutic features were similar across ADI tertiles; after 12 months, treatment intensification allowed better control of hypertension, proteinuria, hypercholesterolaemia, and anaemia with no difference across ADI tertiles. During the subsequent long-term follow-up (10.5 years [interquartile range 8.2-12.6]), 166 renal events and 249 deaths were registered. ADI independently associated with all-cause death (p for trend = 0.020) and non-cardiovascular (CV) mortality (p for trend = 0.045), while CV mortality did not differ (p for trend = 0.252). Risk of composite renal outcomes was similar across ADI tertiles (p for trend = 0.467). The same held true for eGFR decline (p for trend = 0.675)., Conclusions: In CKD patients under regular nephrology care, ADI is not associated with CKD progression, while it is associated with all-cause death due to an excess of non-CV mortality., (© 2020 S. Karger AG, Basel.)

The biological mechanisms through which adherence to Mediterranean Diet (MD) protects against colon cancer (CC) are poorly understood. Evidence suggests that chronic inflammation may be implicated in the pathway. Both diet and CC are related to epigenetic regulation. We performed a nested case-control study on 161 pairs from the Italian component of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, in which we looked for the methylation signals in DNA extracted from leucocytes associated with both CC and MD in 995 CpGs located in 48 inflammation genes. The DNA methylation signals detected in this analysis were validated in a subgroup of 47 case-control pairs and further replicated (where validated) in 95 new pairs by means of pyrosequencing. Among the CpG sites selected a-priori in inflammation-related genes, seven CpG sites were found to be associated with CC status and with MD, in line with its protective effect. Only two CpG sites (cg17968347- SERPINE1 and cg20674490- RUNX3 ) were validated using bisulphite pyrosequencing and, after replication, we found that DNA methylation of cg20674490- RUNX3 may be a potential molecular mediator explaining the protective effect of MD on CC onset. The use of a 'meet-in-the-middle' approach to identify the overlap between exposure and predictive markers of disease is innovative in studies on the relationship between diet and cancer, in which exposure assessment is difficult and the mechanisms through which the nutrients exert their protective effect is largely unknown.

Background: Lipoprotein (a) (Lp [a]) is associated with premature atherosclerosis in menopausal women without metabolic syndrome (MS). MS is the main confounder in the relationship between Lp(a) and atherosclerosis in menopausal women. We have evaluated the relationship between Lp(a) and small dense-low density lipoprotein (sd-LDL) in 228 menopausal women participating to Progetto Atena. Methods: Lp(a) was measured and LDL particle separation was performed: mean LDL diameter and LDL score (% of sd-LDL) particles calculated. Results: Women without MS and elevated Lp(a) have increased number of sd-LDL ( p  < .05) and higher LDL score compared with those below the median of the studied population ( p  < .05). The association between Lp(a) and sd-LDL was evaluated taking into account different adjustment models. Women with elevated levels of Lp(a) show the following OR of having a small LDL diameter (in the lowest quartile): 1.02, p  = .003; adjusted for age; 1.02, p  = .002; adjusted for age, and triglycerides, or a high LDL score (in the highest quartile): 1.02, p  = .006; adjusted for age; 1.02, p  = .002; adjusted for age and triglycerides. Conclusions: In this group of menopausal women without MS, the independent association of Lp(a) with sd-LDL might explain at least in part the association of Lp(a) with premature atherosclerosis.

Background: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer., Methods: An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs., Results: We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 × 10 -12 ) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (OR Q4&#95;vs&#95;Q1  = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (OR Q4&#95;vs&#95;Q1  = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts., Conclusion: We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.

Objectives: Findings relating to dietary intake of n-3 polyunsaturated fatty acids (PUFA) and risk of rheumatoid arthritis (RA) are mixed. Erythrocyte membrane PUFA is an accurate objective biomarker of PUFA status; however, there are little data on erythrocyte membrane PUFA and risk of RA. The objective was therefore to compare erythrocyte membrane PUFA between pre-RA individuals and matched controls from a population-based sample, and specifically to test the hypothesis that higher levels of longer chain n-3 PUFA are associated with lower risk of RA., Methods: The European Prospective Investigation into Cancer and Nutrition (EPIC) is a large European prospective cohort study of apparently healthy populations. We undertook a nested case-control study by identifying RA cases with onset after enrolment (pre-RA) in four EPIC cohorts in Italy and Spain. Confirmed pre-RA cases were matched with controls by age, sex, centre, and date, time and fasting status at blood collection. Conditional logistic regression analysis was used to estimate associations of PUFA with the development of RA, adjusting for potential confounders including body mass index, waist circumference, education level, physical activity, smoking status and alcohol intake., Results: The study analysed samples from 96 pre-RA subjects and 258 matched controls. In this analysis, the median time to diagnosis (defined as time between date of blood sample and date of diagnosis) was 6.71 years (range 0.8-15). A significant inverse association was observed with n-6 PUFA linoleic acid (LA) levels and pre-RA in the fully adjusted model (highest tertile: OR 0.29; 95% CI 0.12 to 0.75; P for trend 0.01). No association was observed with any individual n-3 PUFA, total n-3 PUFA or total n-3:n-6 ratio., Conclusions: Erythrocyte levels of the n-6 PUFA LA were inversely associated with risk of RA, whereas no associations were observed for other n-6 or n-3 PUFA. Further work is warranted to replicate these findings and to investigate if lower LA levels are a bystander or contributor to the process of RA development., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Excessive calorie intake and physical inactivity are considered key determinants of the rapid worldwide increase in obesity prevalence, however the relationship between diet and weight gain is complex. We investigated associations between adherence to a Mediterranean diet and long-term changes in weight and waist circumference in volunteers recruited to the Italian section of the prospective European Prospective Investigation into Cancer and Nutrition (EPIC). We investigated 32,119 cohort members who provided anthropometric measures at recruitment and updated information on recall a mean of 12 years later. Adherence to a Mediterranean diet was assessed using the Italian Mediterranean Index (score range 0-11). Associations between index score and weight and waist changes were assessed by multivariate linear regression models. Risks of developing overweight/obesity and abdominal obesity were investigated by multivariate logistic models. Increasing Italian Mediterranean Index score (indicating better adherence) was associated with lower 5-year weight change in volunteers of normal weight at baseline (β -0.12, 95% CI -0.16 to -0.08 for 1 tertile increase in score), but not in those overweight/obese at baseline (P interaction between Index score and BMI 0.0001). High adherence was also associated with reduced risk of becoming overweight/obese (OR 0.91, 95% CI 0.84-0.99 third vs. first tertile); smaller 5-year change in waist circumference (β -0.09, 95% CI -0.14 to -0.03 for 1 tertile increase in score); and lower risk of abdominal obesity (OR 0.91, 95% CI 0.84-0.99 third vs. first tertile). Adherence to a traditional Italian Mediterranean diet may help prevent weight gain and abdominal obesity.

Factors linked to glucose metabolism are involved in the etiology of several cancers. High glycemic index (GI) or high glycemic load (GL) diets, which chronically raise postprandial blood glucose, may increase cancer risk by affecting insulin-like growth factor. We prospectively investigated cancer risk and dietary GI/GL in the EPIC-Italy cohort. After a median 14.9 years, 5112 incident cancers and 2460 deaths were identified among 45,148 recruited adults. High GI was associated with increased risk of colon and bladder cancer. High GL was associated with: increased risk of colon cancer; increased risk of diabetes-related cancers; and decreased risk of rectal cancer. High intake of carbohydrate from high GI foods was significantly associated with increased risk of colon and diabetes-related cancers, but decreased risk of stomach cancer; whereas high intake of carbohydrates from low GI foods was associated with reduced colon cancer risk. In a Mediterranean population with high and varied carbohydrate intake, carbohydrates that strongly raise postprandial blood glucose may increase colon and bladder cancer risk, while the quantity of carbohydrate consumed may be involved in diabetes-related cancers. Further studies are needed to confirm the opposing effects of high dietary GL on risks of colon and rectal cancers.

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.)

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.)

Background: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment., Methods: The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study., Results: Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals., Conclusions: Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease risk., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

A carbohydrate-rich diet, resulting in high blood glucose and insulin, has been hypothesized as involved in colorectal cancer etiology. We investigated dietary glycemic index (GI) and glycemic load (GL), in relation to colorectal cancer, in the prospectively recruited EPIC-Italy cohort. After a median 11.7 years, 421 colorectal cancers were diagnosed among 47,749 recruited adults. GI and GL were estimated from validated food frequency questionnaires. Multivariable Cox modeling estimated hazard ratios (HRs) for associations between colorectal cancer and intakes of total, high GI and low GI carbohydrate and GI and GL. The adjusted HR of colorectal cancer for highest versus lowest GI quartile was 1.35; 95% confidence interval (CI) 1.03-1.78; p trend 0.031. Increasing high GI carbohydrate intake was also significantly associated with increasing colorectal cancer risk (HR 1.45; 95% CI 1.04-2.03; p trend 0.034), whereas increasing low GI carbohydrate was associated with reducing risk (HR 0.73; 95% CI 0.54-0.98; p trend 0.033). High dietary GI and high GI carbohydrate were associated with increased risks of cancer at all colon sites (HR 1.37; 95% CI 1.00-1.88, HR 1.80; 95% CI 1.22-2.65, respectively), whereas high GI carbohydrate and high GL were associated with increased risk of proximal colon cancer (HR 1.94; 95% CI 1.18-3.16, HR 2.01; 95% CI 1.08-3.74, respectively). After stratification for waist-to-hip ratio (WHR), cancer was significantly associated with GI, and high GI carbohydrate, in those with high WHR. These findings suggest that high dietary GI and high carbohydrate intake from high GI foods are associated with increased risk of colorectal cancer., (© 2014 UICC.)

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: 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.

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.

Background: Dyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers., Methods: We conducted a case-cohort study on participants recruited to four Italian EPIC centers (Turin, Varese, Naples, and Ragusa; 34,148 subjects). A random subcohort of 850 subjects was obtained and 286 colorectal cancer cases were diagnosed. Triglycerides, total and HDL cholesterol were determined in plasma samples obtained at baseline and stored at -196°C; LDL cholesterol was calculated. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox regression models using the Prentice method., Results: The highest tertiles of total (HR 1.66, 95%CI 1.12-2.45) and LDL cholesterol (HR 1.87, 95%CI 1.27-2.76) were associated with increased colorectal cancer risk compared to lowest tertiles. Risks were greater for men than women, and for postmenopausal than premenopausal women. Highest tertiles of total and LDL cholesterol were also significantly associated with increased risks of colon cancer, distal colon cancer, and rectal cancer, but not proximal colon cancer., Conclusions: Our findings suggest that high levels of total and LDL cholesterol increase colorectal cancer risk, particularly in men and postmenopausal women. However additional studies are needed to clarify the role of plasma lipids in these cancers, particularly in view of the conflicting findings of previous studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Colorectal cancer is among the commonest cancers worldwide. Dietary factors have been linked to colorectal cancer risk, however, few studies have evaluated the relationship between a priori dietary patterns and colorectal cancer risk. We evaluated the effect of adherence to a Mediterranean dietary pattern, as measured by the Italian Mediterranean Index, on the risk of colorectal cancer in the 45,275 participants of the Italian section of the EPIC study who completed a dietary questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) for colorectal cancer in relation to categories of Italian Mediterranean Index score were estimated by multivariate Cox models adjusted for known risk factors, on the whole cohort, on men and women and according to cancer subsite. During a mean follow-up of 11.28 years, 435 colorectal cancer cases were identified. The Italian Mediterranean Index was inversely associated with colorectal cancer risk (HR: 0.50; 95% CI: 0.35-0.71 for the highest category compared to the lowest, P-trend: 0.043). Results did not differ by sex. Highest Italian Mediterranean Index score was also significantly associated with reduced risks of any colon cancer (HR: 0.54, 95% CI: 0.36-0.81), distal colon cancer (HR: 0.44, 95% CI: 0.26-0.75) and rectal cancer (HR: 0.41, 95% CI: 0.20-0.81), but not of proximal colon cancer. These findings suggest that adherence to a Mediterranean diet (as measured by the Italian Mediterranean Index) protects against colorectal cancer in general but not against cancer developing in the proximal colon., (Copyright © 2012 UICC.)

The role of fruit and vegetables in breast cancer (BC) development has long been debated. A large variety of vegetables and fruit are consumed by Mediterranean populations, a favourable setting for evaluating the effects of these foods. The association between vegetables and fruit consumption, overall and by specific types, and BC risk was studied in the Italian section of the European Prospective Investigation into Cancer and Nutrition study. Over 31,000 women, aged 36-64 years, recruited in five Italian centers between 1993 and 1998, were available for analyses with dietary and lifestyle information and anthropometric measurements. After a median follow-up of 11.25 years, 1,072 invasive and in situ incident BC cases were identified. Cox proportional hazard models (adjusted for education, anthropometry, reproductive history, hormone replacement therapy, physical activity, alcohol consumption and smoking habits) showed an inverse association between consumption of all vegetables and BC risk (highest vs. lowest quintile HR 0.65; 95% CI 0.53-0.81, P for trend = 0.003). According to subtypes of vegetables, an inverse association emerged for increasing consumption of leafy vegetables (highest vs. lowest quintile HR 0.70; 95% CI 0.57-0.86, P for trend = 0.0001) and fruiting vegetables (highest vs. lowest quintile HR 0.75; 95% CI 0.60-0.94, P for trend = 0.01). An inverse association also emerged with increasing consumption of raw tomatoes (P for trend = 0.03). In contrast, no association of fruit, overall or by subtypes, with BC risk was found. In this Mediterranean population, a clear protective role of increasing vegetables consumption, mainly leafy and fruiting vegetables, on BC risk emerged.

Aims and Background: The DIANA (Diet and Androgens)-5 study is a multi-institutional randomized controlled trial of the effectiveness of a diet based on Mediterranean and macrobiotic recipes and principles, associated with moderate physical activity, in reducing additional breast cancer events in women with early stage invasive breast cancer at high risk of recurrence because of metabolic or endocrine milieu. The intervention is expected to reduce serum insulin and sex hormones, which were associated with breast prognosis in previous studies., Methods: Between 2008 and 2010, the study randomly assigned 1208 patients to an intensive diet and exercise intervention or to a comparison group, to be followed-up through 2015. General lifestyle recommendations for the prevention of cancer are given to both groups, and the intervention group is being offered a comprehensive lifestyle intervention, including cooking classes, conferences, common meals and exercise sessions. Adherence assessments occurred at baseline and at 12 months and are planned at 36 and 60 months. They include food frequency diaries, anthropometric measures, body fat distribution assessed with impedance scale, one week registration of physical activity with a multisensor arm-band monitor, metabolic and endocrine blood parameters. Outcome breast cancer events are assessed through self report at semi annual meetings or telephone interview and are validated through medical record verification., Results: The randomized groups were comparable for age (51.8 years), proportion of ER-negative tumors (22%), axillary node metastasis (42%), reproductive variables, tobacco smoking, blood pressure, anthropometric measurements and hormonal and metabolic parameters., Conclusions: DIANA-5 has the potential to establish whether a Mediterranean-macrobiotic lifestyle may reduce breast cancer recurrences. We will assess evidence of effectiveness, first by comparing the incidence of additional breast cancer events (local or distant recurrence, second ipsilateral or contralateral cancer) in the intervention and in the control group, by an intention-to-treat analysis, and second by analyzing the incidence of breast cancer events in the total study population by compliance assessment score.

Fermented dairy products like yogurt have been suggested to protect against colorectal cancer (CRC). We conducted a prospective study on 45,241 (14,178 men; 31,063 women) volunteers of the EPIC-Italy cohort who completed a dietary questionnaire including specific questions on yogurt intake. During 12 years of follow-up, 289 volunteers were diagnosed with CRC. Hazard ratios (HRs) for the disease and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models, stratified by dietary questionnaire and adjusted for energy intake and other potential confounders. Yogurt intake was inversely associated with CRC risk. For the energy-adjusted model, HR for CRC in the highest versus lowest tertile of yogurt intake was 0.62 (95% CI, 0.46-0.83). In the full model adjusted for energy, simple sugar, calcium, fiber, animal fat, alcohol and red meat intake, as well as body mass index, smoking, education and physical activity, HR was 0.65 (95% CI, 0.48-0.89) in the highest versus lowest tertile. The protective effect of yogurt was evident in the entire cohort, but was stronger in men, although there was no interaction of sex with the yogurt-CRC association (p(interaction) 0.20, fully adjusted model). In our prospective study, high yogurt intake was significantly associated with decreased CRC risk, suggesting that yogurt should be part of a diet to prevent the disease. Investigation of larger cohorts is necessary to reveal any residual confounding of the association of yogurt intake with CRC risk., (Copyright © 2011 UICC.)

The role of environmental carcinogen exposure in breast cancer development has long been suspected, but no specific association has been identified so far. A few molecular epidemiology studies reported that DNA adducts detected by different methods are associated with a modest increase of breast cancer risk. We aimed to evaluate the association between bulky DNA adducts, detected by the (32)P-postlabelling method in peripheral leukocytes, and the risk of developing breast cancer in the female Italian cohorts of the EPIC (European Prospective Investigation into Cancer and nutrition) study. By using a nested case-control design, breast cancer cases identified in the follow-up of over 30,000 women of EPIC-Italy study have been matched to controls by specific criteria. We measured the levels of bulky DNA adducts by the (32)P-postlabelling method in peripheral leukocytes donated at enrolment. Conditional regression analyses adjusted for selected potential confounders were used. Results on DNA adduct levels were available for 292 cases and 292 matched controls. The mean DNA adduct levels were similar in both groups (P=0.62). Multivariate regression analyses failed to show any significant association between bulky DNA adducts and breast cancer. Our results do not support any association of breast cancer risk with exposure to environmental carcinogens as measured through the levels of bulky DNA adducts in pre-diagnostic white blood cells. Larger studies by using different methods and/or biomarkers are needed to better evaluate the role of specific environmental carcinogens in breast carcinogenesis.

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.

Experimental studies suggest that oxidative stress and systemic inflammation are involved in the pathogenesis of ischemic stroke. Consuming a diet with a high total antioxidant capacity (TAC) has been related to reduced inflammation and increased circulating antioxidants in cross-sectional and randomized intervention studies. This study investigates the relation between dietary TAC and risk of ischemic and hemorrhagic stroke in 41,620 men and women not previously diagnosed with stroke or myocardial infarction, representing the Italian segment of the European Prospective Investigation into Cancer and Nutrition. Controlling for potential confounders, a diet rich in TAC was associated with a reduction in HR for all types of stroke, but this association was only marginally significant (P-trend = 0.054). When only ischemic stroke cases were considered, data suggest a stronger inverse association with dietary TAC, with HR = 0.41 (95% CI = 0.23-0.74). Regarding single antioxidants, data from subanalyses on stroke types suggest that vitamin C is significantly associated with a decreased risk of ischemic stroke [HR = 0.58 (95% CI = 0.34-0.99)], whereas vitamin E was associated with increased HR of hemorrhagic stroke in the highest tertile of intake [HR = 2.94 (95% CI = 1.13-7.62)]. In conclusion, our findings suggest that antioxidants may play a role in reducing the risk of cerebral infarction but not hemorrhagic stroke. However, a high intake of vitamin E could be positively associated to the risk of brain hemorrhagic events; therefore, more focused investigations about this observation are needed.

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: Social factors could offer useful information for planning prevention strategy for cardiovascular diseases. This analysis aims to explore the relationship between education, marital status and major cardiovascular risk factors and to evaluate the role of social status indicators in predicting cardiovascular events and deaths in several Italian cohorts., Methods: The population is representative of Italy, where the incidence of the disease is low. Data from the Progetto CUORE, a prospective study of cohorts enrolled between 1983-1997, were used; 7520 men and 13127 women aged 35-69 years free of previous cardiovascular events and followed for an average of 11 years. Educational level and marital status were used as the main indicators of social status., Results: About 70% of the studied population had a low or medium level of education (less than high school) and more than 80% was married or cohabitating. There was an inverse relationship between educational level and major cardiovascular risk factors in both genders. Significantly higher major cardiovascular risk factors were detected in married or cohabitating women, with the exception of smoking. Cardiovascular risk score was lower in married or cohabitating men. No relationship between incidence of cardiac events and the two social status indicators was observed. Cardiovascular case-fatality was significantly higher in men who were not married and not cohabitating (HR 3.20, 95%CI: 2.21-4.64). The higher cardiovascular risk observed in those with a low level of education deserves careful attention even if during the follow-up it did not seem to determine an increase of cardiac events., Conclusions: Preventive interventions on cardiovascular risk should be addressed mostly to people with less education. Cardiovascular risk score and case-fatality resulted higher in men living alone while cardiovascular factors were higher in women married or cohabitating. Such gender differences seem peculiar of our population and require further research on unexpected cultural and behavioural influences.

Background/objectives: Body mass index (BMI), waist circumference (WC), body weight modification, and rate of weight increase over 10 years were evaluated in relation to high-sensitive C-reactive protein (hs-CRP) to assess the association of cross-sectional or longitudinal estimates of obesity/overweight with levels of circulating CRP, a well established and standardized marker of low-grade inflammation, in relation to cardiovascular risk., Subjects: This study included a subgroup of 390 menopausal women participating in a large currently ongoing epidemiological study (Progetto Atena; N=5062)., Results: At the final visit, women in the third tertile of BMI, compared with those in the first tertile, showed the following odds ratio (OR) of having high hs-CRP values: III vs I tertile OR, 3.55; 95% confidence interval, 1.94-6.49, P<0.001, adjusted for age, and metabolic syndrome. Similar results were obtained when we evaluated women in the third tertile of WC, or those in the highest group of estimated weight increase, relative to their weight at age 20 years or in the group of highest rate of weight increase over 10 years of observation (weight at the final visit-weight at the baseline visit divided by time in months between visits)., Conclusions: The independent relations between different markers of overweight/obesity and elevated hs-CRP consistently indicate that high (above 1.5 mg l(-1), median) hs-CRP is a major biochemical counterpart of cross-sectional or longitudinal estimates of increased adipose tissue mass.

Background: The aim of this study was to build risk charts for the assessment of cardiovascular mortality of the CUORE project, an Italian longitudinal study, and to compare them with the systematic coronary risk evaluation (SCORE) project charts for low risk European countries., Design: Random population samples enrolled in the 1980s and 1990s in Italy were included in the analysis: 7,520 men and 13,127 women aged 35-69 years without previous cardiovascular events and with a mean follow-up period of 10 years for cardiovascular disease. ICD-9 codes of death certificates similar to those of the SCORE project were considered when they appear as first cause of death., Methods: Sex-stratified Cox proportional hazard model including age, systolic blood pressure, ratio between total and HDL cholesterol, and smoking habit as risk factors was used to assess cardiovascular mortality., Results: Analysis showed that all risk factors included in the model were statistically significant. The corresponding area under the receiver operating characteristic curve was 0.825 (95% confidence interval: 0.803-0.846) for men and 0.850 (0.823-0.877) for women. The CUORE project charts yielded similar results to the corresponding charts of the SCORE project: Lin's coefficient was 0.929 for men and 0.935 for women., Conclusion: The comparison between CUORE and SCORE mortality risk charts shows that SCORE charts reflect quite well the Italian cardiovascular mortality and, correspondingly, Italian cohorts of the CUORE project are quite representative of European countries at low risk for cardiovascular mortality.

Background: Recently, biological markers related to the immune system such as cytokines have been studied to further understand the etiology of non-Hodgkin Lymphoma (NHL). However, to date, there are no studies that have studied cytokine levels prospectively in relation to NHL risk in the general population., Methods: Using bead-based immunoassays, plasma levels of 11 cytokines, 4 chemokines, and 1 adhesion molecules were measured in prediagnostic blood samples of 86 NHL cases and 86 matched controls (average time between blood collection and diagnosis, 4.5 y). Conditional logistic regression adjusted for body mass index and alcohol consumption was used to analyze the association between individual plasma cytokine levels and the risk of developing NHL., Results: In multivariate models, excluding cases diagnosed within 2 years after inclusion, we observed a significant association for interleukin 2 (IL2; P trend = 0.004), interferon (IFN)-gamma (P trend = 0.05), and intercellular adhesion molecule (ICAM) (P trend = 0.04). Subanalyses of B-cell NHL patients showed a significant association with IL2 (P trend = 0.003), tumor necrosis factor-alpha (TNF-alpha; P trend = 0.03), and ICAM (P trend = 0.04) and a borderline association with IL5 (P trend = 0.07) and IFN-gamma (P trend = 0.08)., Conclusions: The results of this study suggest, in a prospective setting, a possible association between plasma levels of IL2, ICAM, IFN-gamma, and TNF-alpha with NHL risk and provide some evidence that risk of NHL might be related to a downregulation of T helper 1 cytokines., Impact: Identification of subtle changes in immune response regulation quantified by plasma cytokine levels possibly provides new insights in the etiology of NHL., (Copyright 2010 AACR.)

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.

Background: The CUORE Project, an Italian longitudinal study, and the SCORE Project use similar methodology in data collection of cardiovascular risk factors and events. The aim of this study was to build the CUORE Project risk charts for the assessment of cardiovascular mortality and to compare them with the SCORE charts., Methods: Random population samples enrolled between 1980 and 1990 in Italy were included in the analysis: 7520 men aged 35-69 years without previous cardiovascular events with a mean follow-up period of 10 years for cardiovascular disease. ICD-9 codes of death certificates similar to those of the SCORE Project were considered in the analysis when they appear as first cause of death. Gender stratified Cox proportional hazard models were used to assess cardiovascular mortality, including age, systolic blood pressure, total cholesterol (or total-to-HDL cholesterol ratio) and smoking habit as risk factors., Results: Results from gender stratified analysis considering total cholesterol showed that all risk factors included in the cardiovascular mortality Cox model of the CUORE Project were statistically significant. The correspondent area under the ROC curve was 0.822 (95% confidence interval 0.800-0.844) for men. The CUORE Project charts were quite similar to the correspondent charts of the SCORE Project: Lin's concordance coefficient was 0.964. Risk range of non-smoker men was 0-17% for the CUORE cardiovascular mortality risk chart (0-14% for the SCORE chart); risk range of smokers was 0-25% for the CUORE cardiovascular mortality risk chart (0-26% for the SCORE chart). Similar results were observed for the chart with total-to-HDL cholesterol ratio., Conclusions: The comparison between the CUORE and SCORE mortality risk charts demonstrates that the SCORE charts reflect quite well Italian cardiovascular mortality and, correspondingly, Italian cohorts of the CUORE Project are quite representative of European countries with a low risk of cardiovascular mortality.

Consumption of dairy products seems to increase the risk of cancer at several sites, while intake of cruciferous vegetables could have protective effects. However, these dietary intakes are subject to measurement error, and associations with cancer could be due to confounders. Mendelian randomization has been suggested as a way to overcome confounding by exploiting the random allocation of alleles from parents to offspring. In mid-2006, the authors conducted a study of allele frequencies for the lactase (LCT) and taste receptor, type 2, member 38 (TAS2R38) genes, including 634 volunteers recruited (1992-1998) from the Italian branch of the European Prospective Investigation into Cancer and Nutrition. The authors hypothesized that there would be a lower milk intake among carriers of the LCT CC genotype and a different intake of cruciferous vegetables among carriers of the TAS2R38 variant. Overall, the frequency of the LCT T allele was higher in northern Italy than in southern Italy. Food intake was associated with gene variants. An association was evident for ice cream and LCT variants (p = 0.004); less so for milk intake. In addition, the TAS2R38 variant showed a geographic gradient and an association with cruciferous vegetable intake. These results suggest that the LCT and TAS2R38 variants are good candidates for Mendelian randomization studies of cancer and other health outcomes.

Objective: To evaluate long-term mortality rate of anorexia nervosa (AN) patients in a southern Italy population compared to the most recent literature., Design: Retrospective and review setting., Patients and Interventions: One hundred and forty-seven female AN patients, consecutively admitted from 1994 to 1997 to the Outpatient Unit, were re-examined between June and November 2003. Our data are compared with 10 other studies published since 1988., Results: One hundred and twenty-three deaths in 2240 patients, amounting to a total mortality rate of 5.25% were reported in the literature. Deaths due to suicide, AN-related and AN-unrelated diseases were 1.20, 3.07 and 0.98%, respectively. After correcting for unrelated deaths, mortality rate was 4.27%. In our 8-year follow-up, we found a mortality rate of 2.72% (1.82% after correcting for unrelated deaths). Standardized mortality ratio was 9.7., Conclusion: We interpret our favourable findings as a consequence of an integrated, clinical-nutritional and psychiatric approach. Finally, considering AN demographic characteristics, that is young female subjects in Westernized societies, mortality rate is confirmed to be dramatically high.

Background: Cardiovascular risk factor research has recently broadened its focus based on new data indicating the benefits of low risk, i.e. favorable levels of all major risk factors. The aims of this study were to assess further the relation of low risk to coronary heart disease risk, and implications for prevention., Design: We conducted a prospective population-based Italian study, of 7438 men and 13 009 women aged 35-69 years, with a mean follow-up of 10.4 years and validated first coronary events., Methods: Baseline coronary heart disease risk was classified into three categories: low risk; unfavorable but not high risk; and high risk. To analyze the relation of these risk profiles to coronary heart disease incidence, age-adjusted, sex-averaged coronary heart disease incidence was calculated for persons free of coronary heart disease and stroke, stratified as baseline low risk, unfavorable but not high risk or high risk. To assess the independent relationship of individual risk factors to coronary heart disease incidence, multivariate proportional hazards models were computed for combinations of risk factors., Results: Only 2.7% of participants met low risk criteria; 81.4% were high risk. Age-adjusted coronary heart disease incidence for the whole cohort was 37.1 out of 10000 person-years (men 59.0; women 15.3). No coronary heart disease events occurred in low-risk men, only two in low-risk women. For women and men who were not high risk, the age-sex standardized coronary heart disease rate was 62% lower than for high-risk participants. Blood pressure, need for antihypertensive medication, smoking, hyperglycemia, diabetes, total and high-density lipoprotein cholesterol were independently related to coronary heart disease risk., Conclusions: Favorable levels of all modifiable readily measured risk factors - rare among Italian adults - assure minimal coronary heart disease risk. Population-wide prevention is needed, especially improved lifestyles, to increase the proportion of the population at low risk.

Background: Over the last decades a change in physical activity habits of the Italian population has been observed. The aim of this study was to compare occupational and leisure-time physical activity, to assess the relationship between physical activity and cardiovascular risk factors and the variation in cardiovascular risk profile measured 20 years apart in the Italian population., Methods: In two populations aged 35-69 years (MATISS 1984-1987: 2041 men, 2424 women; OEC 1998-2002: 4214 men, 4206 women) gender-specific levels of occupational (occupational physical activity [OPA]-light, OPA-moderate, OPA-heavy) and leisure-time (leisure-time physical activity [LTPA]-low, LTPA-moderate, LTPA-high) physical activity were compared. Relationship between physical activity and cardiovascular risk factors was evaluated in the two samples using logistic regression models adjusted for age, heart rate, educational level and other possible confounding variables in men and women separately. The 10-year cardiovascular risk was assessed in the two periods and in different physical activity strata using the Progetto CUORE risk score., Results: Comparing the two studies, prevalence of OPA-low had decreased, whereas the prevalence of LTPA-low had increased. With increasing LTPA blood pressure, heart rate and glycemia decreased, whereas high-density lipoprotein-cholesterol increased with a positive effect on obesity, smoking habit and cardiovascular risk., Conclusions: Over the last 20 years, physical activity apparently changed: currently men and women dedicate more time to physical activity during leisure-time, and are less active at work. More active people have lower levels of major cardiovascular risk factors. Societal efforts are needed to increase physical activity levels in the population.

Recently, the focus of research on cardiovascular risk factors has broadened because of new data demonstrating benefits of low risk (i.e., favorable) levels of all major modifiable risk factors. Most data on low risk relate to coronary heart disease, not stroke. This population-based, 12-sample, Italian study (Progetto CUORE, 1983-2002), with 10-year follow-up, assessed the relation of low risk to stroke and implications for prevention. At baseline, women and men were 35-69 years of age. Only 3% were low risk; 80% were high risk. Overall, stroke incidence rates were 20.7 for men and 9.6 for women per 10,000 person-years. No strokes occurred in low risk participants, and stroke incidence was low with borderline elevation of only one risk factor. Four modifiable risk factors--elevated blood pressure, smoking, diabetes, and high total cholesterol/high density lipoprotein cholesterol ratio--related independently to stroke risk. For those at low risk or who had only one unfavorable (but not high) risk factor, the stroke rate was 76% lower than for high risk participants; for all persons not at high risk, the stroke rate was 57% lower than for those at high risk. Results show that favorable risk factor levels assure minimal stroke risk. Population-wide prevention is needed, especially improved lifestyles, to increase the prevalence of low risk.

Background: To evaluate 10-year cardiovascular risk, the risk chart and the individual risk score from the CUORE Project were recently introduced in Italy. These tools differ as for age range and some risk factors. Therefore, the aim of this study is to evaluate the difference between the global absolute risk assessed by the risk chart and the individual risk score using the data collected through the Osservatorio Epidemiologico Cardiovascolare (OEC)., Methods: From the Osservatorio Epidemiologico Cardiovascolare sample, 6508 people aged 40-69 years without clinical manifestations of atherosclerosis were selected. Cardiovascular risk was assessed using risk chart and individual risk score and the 10-year risk was categorized in six classes (< 5%, 5-9%, 10-14%, 15-19%, 20-29%, > or = 30%). As coefficient of agreement between risk chart and individual risk score, Cohen kappa statistic was computed using the Cicchetti-Allison weights (k(w))., Results: From contingency tables of the two methods distribution, k(w) was 0.71 (p < 0.0001 and 95% confidence interval 0.70-0.72). Using the 20% risk threshold reported in Nota 13 of Agenzia Italiana del Farmaco and excluding persons who were treated for hyperlipemia refunded regardless of their chart or individual score estimation of cardiovascular risk, the differences between the two tools classification resulted in the 2.6% of the sample (1.4% were assessed as at non-high risk [< 20%] using the risk chart and at high risk using the individual risk score, and the opposite for 1.2%)., Conclusions: Classification difference between risk charts and the individual risk score is quite small. Updating of predictive functions of two tools could improve their concordance also for individual evaluation, including older people and better reflecting current Italian lifestyle.

Background: The aim of this study was to assess the 10-year cardiovascular risk categories using risk chart, recently set up by the National Institute of Health in the population examined by the Cardiovascular Epidemiologic Observatory., Methods: 3745 men and 3664 women aged 40-69 years were classified into five risk categories (< 5 %; 5-10%; 10-15%; 15-20%; > or = 20%) taking into account age, smoking habit, history of diabetes, systolic blood pressure, serum cholesterol and excluding those already under treatment for hypertension and hypercholesterolaemia or experienced a previous major cardiovascular event (1937 persons: 955 men, 982 women)., Results: Proportion of people estimated at risk in 10 years > or = 20% is minimal in the youngest age range, increases in adulthood, duplicates in smokers and is higher in diabetics. In non-diabetic men that proportion varies between 3.4% in non-smokers and 5.6% in smokers. All women at risk are already under specific treatment., Conclusions: Cardiovascular Epidemiologic Observatory data allowed to assess the expected proportion of individuals at risk in 10 years > or = 20%. Besides attention to high-risk individuals, preventive measures supporting a healthier lifestyle in the general population must be adopted, considering that it will produce the greatest number of events.

Background: The aims of this paper are to derive a 10-year coronary risk predictive equation for adult Italian men, and to assess its accuracy in comparison with the Framingham Heart Study (FHS) and PROCAM study equations., Methods: The CUORE study is a prospective fixed-cohort study. Eleven cohorts, from the north and the centre-south of Italy, had been investigated at baseline between 1982 and 1996, adopting MONICA methods to measure risk factors. Among this sample of 6865 men, aged 35-69 years and free of coronary heart disease (CHD) at baseline, 312 first fatal and non-fatal major coronary events occurred in 9.1 years median follow-up. Calibration, as the difference between 10-year predicted and actual risk, and discrimination, as the ability of the risk functions to separate high-risk from low-risk subjects, have been assessed to compare accuracy of the FHS, the PROCAM, and the CUORE study equations., Results: The best CUORE equation includes age, total cholesterol, systolic blood pressure, cigarette smoking, HDL-cholesterol, diabetes mellitus, hypertension drug treatment, and family history of CHD (area under the ROC curve = 0.75). The uncalibrated estimates of the 10-year risk in this CUORE follow-up data were 0.093 and 0.109 higher (P < 0.05) from the Framingham and PROCAM risk scores, respectively, than the Kaplan-Meier estimate for CUORE, indicating risk overestimates for both equations. Standard recalibration techniques improved accuracy of the FHS equation only. PROCAM overestimates were prominent in the higher risk deciles. With an alternative method for recalibration better risk estimates were obtained, but a cohort study was needed to obtain a properly calibrated risk equation., Conclusions: The CUORE Project predictive equation showed better accuracy of the FHS and PROCAM equations, overcoming frequently reported risk overestimates. The CUORE equation may be adopted to identify men with high coronary risk in Italy.

Objective: this study evaluates the appropriateness of the clinical activities performed during hospitalization of patients with atherosclerosis without complications (Disease-related Group - DRG 133 in the Italian National Health System), at the Policlinico Universitario Federico II, Naples., Design and Setting: coded criteria PRUO - (Protocol for the revision of hospital use) have been used in order to quantify the appropriateness of 94 randomly selected clinical reports for 2001 and 2002. Two independent examiners have evaluated clinical reports, and a supervisor has decided upon the disagreements (majority rule). Appropriateness was rated by tertiles of age and hospital-stay length., Results: global appropriateness was 68%, and increased 93% when it was related to admission days and 64% when was related to the duration of the hospital-stay. Appropriateness of the use of hospital for DRG 133 diagnosis was more frequent for patients older than 70 years and for short duration of hospital stay. Logistic regression has confirmed the trends, indicating a robust statistical significance for the duration of hospital stay but not for age.

Background: Whether the practice of family doctors of assessing the global cardiovascular risk profile improves the knowledge of cardiovascular risk factors and the attitude to lifestyle change in patients' secondary cardiovascular prevention is unknown., Methods: We evaluated subjects who visited their family doctors and those with self-reported cardiovascular disease in the urban area of Naples, Italy. Patients self-administered a simple standard questionnaire to evaluate their knowledge of cardiovascular risk factors and of simple lifestyle modifications to reduce the cardiovascular risk burden. For each participant, family doctors, blinded to the information provided by patients, had to provide a global coronary risk based on the risk factors recorded in their electronic database, or report the missing information., Results: The study sample comprised 560 subjects, 61% male, with mean age 60 +/- 9 years. Angina pectoris (49%) and myocardial infarction (40.9%) were the most frequently self-reported cardiovascular diseases in the study sample. The self-reported data revealed that 46% of the sample was overweight and an additional 20% overtly obese. Among those who self-reported arterial hypertension, approximately 11% admitted that they were unaware of their blood pressure, and 26% believed that they were normotensive but reported a recently detected blood pressure > 140/90 mmHg. Approximately 8% were not aware of whether they had high cholesterol levels, and among those who declared having normal cholesterol levels, 9% referred levels > 200 mg/dl. Of the sample, 22% self-reported diabetes, but 7% did not know whether they were diabetic or not. Thirty percent of the sample were smokers and among these, 40% smoked > 20 cigarettes/day. A low level of education was reported in 66% of the study sample. Women were more frequently obese, more often reported high cholesterol levels, had a low level of education and achieved a lower score from the questionnaire on knowledge of cardiovascular risk factors than men. Patients > 55 years more often reported an elevated blood pressure among those who defined themselves as normotensive, and achieved a lower score from the questionnaire on knowledge of cardiovascular risk factors than younger patients., Conclusions: With regard to secondary cardiovascular prevention, the study population was found to have insufficient knowledge of cardiovascular risk factors and of the correct approach to reduce their global risk despite the fact that the attitude of their family doctors in detecting and recording risk factors was above average.

Frequent consumption of fresh fruit and vegetables, and polymorphisms in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) and other metabolic genes have been shown to modulate cancer risk at some sites. We have shown recently that DNA adducts, a reliable indicator of genotoxic damage and, possibly, of cancer risk, are modulated by plasma levels of selected micronutrients. Here we further investigate the association between DNA adduct levels and consumption of major food groups and foods, and the estimated dietary intake of nutrients, taking into account the possible modifying effect of metabolic polymorphisms, in a larger sample of 634 healthy adults enrolled in a prospective study in Italy. DNA adducts and five polymorphic metabolic genotypes (GSTM1, GSTT1, NAT2, CYP1A1 and MTHFR) were determined in peripheral leukocytes by using 32P-postlabeling technique and PCR methods. DNA bulky adducts (mean: 7.82 +/- 0.40/10(9) nt) were detected in 482/634 samples (76.0%). Overall, DNA adduct levels were significantly and inversely associated with the intake of raw leafy vegetables (P = 0.02), non-citrus fruits (P = 0.04), potassium (P = 0.01) and beta-carotene (P = 0.05). No association was evident with the five genotypes. Stratification by GSTM1 genotype showed strong inverse associations of DNA adduct levels with increasing consumption of all vegetables combined (P = 0.04), leafy vegetables (P = 0.004), raw leafy vegetables (P = 0.002) and fish (P = 0.03) among 307 GSTM1-null subjects; strong inverse associations also emerged with estimated dietary intakes of beta-carotene (P = 0.004), vitamin E (P = 0.004), niacin (P = 0.02) and potassium (P = 0.01). In contrast, no association emerged among 295 subjects with a GSTM1-wild genotype. Overall, statistically significant interactions in predicting DNA adduct levels were observed between the GSTM1-null genotype and consumption of leafy vegetables (P = 0.01), white meat (P = 0.04), and intake of vitamin C (P = 0.04), vitamin E (P = 0.05) and beta-carotene (P = 0.02). Our results suggest that the role of a diet rich in antioxidants in preventing or reducing DNA adduct formation is restricted to subjects lacking the detoxifying activity of GSTM1 isoenzyme (approximately 50% of the general population).