[Dietary habits and social differences: the experience of EPIC-Italy]. / Abitudini alimentari e disuguaglianze sociali: l'esperienza della collaborazione EPIC-Italia.

OBJECTIVES: to investigate the impact of socioeconomic status on dietary habits in Italy. DESIGN: large Italian multicentric prospective cohort study. SETTING AND PARTICIPANTS: more than 45,000 subjects recruited between 1993 and 1998 in five Italian centres (Turin, Varese, Florence, Naples, and Ragusa). Dietary habits, educational level, and other characteristics were collected at baseline using standardised questionnaires. MAIN OUTCOME MEASURES: dietary habits collected for the EPIC study, grouped by food type and summarised by a Mediterranean dietary index. RESULTS: we observed differences in dietary habits and in lifestyle habits by tertile of educational level. Principally, we noticed a positive association between higher education and healthy dietary habits (reduction in intake of processed meat, bread and rice, sweet drinks; increase in intake of fruit and vegetables, yoghurt, fish, olive oil, and tea). CONCLUSION: a relationship between educational level and dietary habits is confirmed also in Italy, even if differences due to gender and residence area are present. This study shows an important role of dietary habits in health inequalities of the population with lower socioeconomic status.

[Dietary habits and cardiovascular disease: the experience of EPIC Italian collaboration]. / Abitudini alimentari e malattie cardiovascolari: l'esperienza della collaborazione EPIC-Italia.

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.

Italian Mediterranean Index and risk of colorectal cancer in the Italian section of the EPIC cohort.

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.

Olive oil intake and breast cancer risk in the Mediterranean countries of the European Prospective Investigation into Cancer and Nutrition study.

Although there is some evidence suggesting that olive oil could reduce breast cancer (BC) risk, the epidemiological data are still relatively limited, not entirely consistent and mainly based on case-control studies. Therefore, we prospectively assessed the association between olive oil and BC risk in postmenopausal women from the Mediterranean cohorts within the European Prospective Investigation into Cancer and Nutrition. The analysis included 62,284 postmenopausal women recruited from Spain, Italy and Greece who had complete dietary data (collected from validated country-specific dietary questionnaires). The risk of BC (overall and by hormone receptor subtypes) was assessed using hazards ratios (HRs) obtained from Cox proportional hazards regression, while adjusting for known BC risk factors. After a mean follow-up of 9 years, 1,256 women were diagnosed with a primary incident invasive BC. The multivariate HRs for BC risk by olive oil intake (highest vs. lowest tertile of g/day/2,000 kcal) were 1.07 (95% CI = 0.91-1.25) in the adjusted model, 1.06 (95% CI = 0.91-1.24) in the model additionally adjusted for reproductive-related factors and 1.10 (95% CI = 0.92-1.31) for the model additionally adjusted for dietary factors. There was no association between olive oil and risk of estrogen or progesterone receptor-positive tumors, but a suggestion of a negative association with estrogens and progesterone receptor-negative tumors. The results from our prospective study showed that olive oil consumption during adult life was not associated with the risk of BC. However, larger prospective studies are still needed to explore possible differences related to hormone receptor status.

Fruit and vegetables consumption and breast cancer risk: the EPIC Italy study.

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.

Bulky DNA adducts and breast cancer risk in the prospective EPIC-Italy study.

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.

DNA methylation, colon cancer and Mediterranean diet: results from the EPIC-Italy cohort.

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.

Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk.

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 (ORQ4_vs_Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4_vs_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.

Adherence to a Mediterranean diet and long-term changes in weight and waist circumference in the EPIC-Italy cohort.

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 (ß -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 (ß -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.

Life-course socioeconomic status and DNA methylation of genes regulating inflammation.

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.

Twenty-four-hour urinary excretion of ten pesticide metabolites in healthy adults in two different areas of Italy (Florence and Ragusa).

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.

Cancer incidence in EPIC-ITALY at first follow-up.

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.

Urinary 1-hydroxypyrene and t,t-muconic acid as biomarkers of exposure to environmental pollutants in two areas in Italy (EPIC-Florence and Ragusa).

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.

Correlates of age at natural menopause in the cohorts of EPIC-Italy.

A large number of studies have investigated the factors correlated to age at natural menopause in several populations. However, information on genetics and life-style factors influencing the age of onset of menopause in different populations is of current scientific interest. Specifically, for Italian women there are no large population-based data. The EPIC-Italy collaboration is a source of data of this kind; moreover, the geographical distribution of the cohorts (recruited in northern, central and southern Italy) is an added value as regards the scientific interest of these data. A number of biological and life-style-related factors have been analyzed to evaluate their association to the age at natural menopause in 14,454 menopausal women of the EPIC-Italy collaboration. As regards life-style and environmental factors, the main results are: a) women living in different areas of the country have different ages of onset of natural menopause; b) educational level is significantly associated to this age and may explain part of the between-center difference; c) cigarette smoking appears as a major correlate and probably determinant of the age at natural menopause across all the Italian cohorts; d) alcohol consumption does not have any relationship with the age at natural menopause; e) the use of oral contraceptives may influence age at natural menopause. As regards biological factors, short cycles and low parity have been found associated with earlier menopause. Overall, the results concerning menstrual cycles, parity, and cigarette smoking are consistent with the hypothesis that the number of oocytes in the ovary is pre-determined and any acceleration or impairment of the ovarian function leads to reduce the duration of the reproductive life.

Determinants of exposure to environmental tobacco smoke in 21,588 Italian non-smokers.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is associated with an increased risk of lung cancer, ischemic heart disease and respiratory diseases in non-smokers. Exposure is likely to be uneven in the population. Knowledge of its distribution is important for a better planning of preventive activities. METHODS: In the context of the Italian branch of the EPIC prospective investigation, in which we enrolled 47,000 volunteers, we have surveyed exposure to ETS and its determinants (age, social class, occupation). The purpose of the present paper is to contribute to identify the main sources of exposure in Italy. RESULTS: We found, in a sample of 21,588 Italian non-smokers, a prevalence of 0.337 (95% confidence interval, 0.336-0.337) in women and 0.537 (0.529-0.544) in men. Exposure was defined as at least 1 hr/day for at least one year. Exposure at work is by far the commonest source of exposure to ETS, with a strong difference between full-time and part-time jobs. The distribution of exposure by social class was uneven, with statistically significant odds ratios for higher social groups in the order of 0.4-0.5. White-collar workers are the occupational category mostly exposed, suggesting that the implementation of anti-smoking legislation is still incomplete in Italian offices. CONCLUSIONS: The uneven distribution of ETS in the population is a matter of concern, since it contributes to the unequal distribution of health in different social groups.

Relationship between plasma fatty acid composition and diet over previous years in the Italian centers of the European Prospective Investigation into Cancer and Nutrition (EPIC).

Fatty acid levels in plasma phospholipids were related to food intake over the previous year as estimated by semiquantitative food frequency questionnaires compiled by 280 men and 246 women from the EPIC centers of Varese, Turin, Florence and Ragusa (Italy). Fatty acid content was determined by gas chromatography and analyzed in relation to age, sex and center. The most important finding was that plasma monounsaturated fatty acid levels, mainly oleic acid, were associated with olive oil consumption (r = 0.28 men, r = 0.19 women, both P <0.01). To our knowledge, this is the first time that these non-essential plasma fatty acids have been related to their dietary source in a population eating a varied and freely chosen diet. We confirmed that long-chain n-3 fatty acids in plasma phospholipids are associated with fish consumption and that odd chain 15 : 0 and 17 : 0 fatty acid levels are associated with dairy products and pizza-with-mozzarella consumption. N-6 polyunsaturated fatty acid levels reflected dietary intake of seed oils, mayonnaise and biscuits. Alcohol intake was positively associated with palmitic and palmitoleic acid and negatively associated with linoleic acid. These associations suggest indirect relations between alcohol consumption and other features of diet, and also that ethanol has an effect on fat metabolism. We found numerous indirect relationships (ie, not due to dietary consumption of food sources of the fatty acids) between plasma fatty acids and diet, which we propose as due to the influence of complex life-style factors.

A molecular epidemiology project on diet and cancer: the EPIC-Italy Prospective Study. Design and baseline characteristics of participants.

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.

Incidence of pleural mesothelioma in a community exposed to fibres with fluoro-edenitic composition in Biancavilla (Sicily, Italy).

INTRODUCTION: Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite. MATERIALS AND METHODS: Malignant mesothelioma case series and incidence were examined to evaluate the disease burden on Biancavilla inhabitants. RESULTS: The incidence of pleural mesothelioma in Biancavilla is steadily higher than in the Sicilian Region, risk estimates are more elevated in women than in men, the most affected age class is constituted by subjects aged less than 50. DISCUSSION AND CONCLUSIONS: Environmental exposure to fibres with fluoro-edenitic composition appears to be causally related to the elevated mesothelioma occurrence in Biancavilla. In this frame, environmental clean-up is the main goal to be pursued in public health terms. A contribution of scientific research to public health decision making with respect to priority setting for environmental clean-up can derive from some further selected epidemiological investigations.

Colorectal cancer risk and dyslipidemia: a case-cohort study nested in an Italian multicentre cohort.

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.

Elevated levels of D-dimers increase the risk of ischaemic and haemorrhagic stroke. Findings from the EPICOR Study.

Elevated D-dimer levels are reportedly associated with coronary artery disease. It was the study objective to investigate the association of baseline D-dimer levels with strokes that occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Using a nested case-cohort design, a centre--stratified sample of 832 subjects (66 % women, age 35-71) was selected as subcohort and compared with 289 strokes in a mean follow-up of nine years. D-dimers were measured by an automated latex-enhanced immunoassay (HemosIL-IL). The multivariable hazard ratios were estimated by a Cox regression model using Prentice method. Individuals with elevated D-dimer levels had significantly higher risk of incident stroke. It was evident from the second quartile (D-dimers > 100 ng/ml) and persisted almost unchanged for higher D-dimers (hazard ratio [HR] 2.10, 95 % confidence interval [CI]: 1.28-3.47; 2.42, 95 %CI: 1.44-4.09 and 2.10, 95 %CI: 1.27-3.48 for the second, third or fourth quartile compared with the lowest quartile, respectively). The association was independent of several confounders, including triglycerides and C-reactive protein. No differences were observed in men and women (P for interaction=0.46), in hypertensive or non-hypertensive subjects (P for interaction=0.88) or in subjects with low (< 1 mg/l) or elevated (≥ 1 mg/l) C-reactive protein (P for interaction=0.35). After stratification for stroke type, the hazard ratio for every standard deviation increase was statistically significant both for ischaemic (1.21; 95 %CI: 1.01 to 1.45) and haemorrhagic (1.24; 95 %CI: 1.00 to 1.65) strokes. In conclusion, our data provide clear evidence that elevated levels of D-dimers are potential risk factors not only for ischaemic but also for haemorrhagic strokes.