A 5-Year Follow-Up of a Cohort of Italian Alcoholics: Hospital Admissions and Overall Survival.

BACKGROUND: Alcohol use disorders (AUDs), including alcohol dependence and alcohol abuse defined according to specific DSM-IV and ICD-10 criteria, can be potentially lethal, because they are associated with several medical and psychiatric conditions. This study aimed to describe the causes of hospitalization of a large cohort of subjects with alcohol dependence (alcoholics) enrolled in Florence (Italy) over a 5-year follow-up period and to evaluate the effect of hospitalization on overall survival. METHODS: One thousand one hundred and thirty alcoholics, newly diagnosed from 1997 to 2001, were linked to the Regional Mortality Registry for update of vital status as of December 31, 2006, and to the Hospital Discharge electronic archives of the Regional Health System of Tuscany to verify hospital admissions (HAs) during the 5-year postcohort enrollment follow-up. Kaplan-Meier survival and Cox regression analyses were performed to evaluate any association of HA with overall survival. RESULTS: A total of 3,916 new hospitalizations occurred during the 5-year follow-up. Most alcoholics (70.6%) reported at least 1 new hospitalization, with a first hospitalization rate of 61.7 per 100 person-years in the first year of follow-up. The mean number of hospitalizations per admitted subject was 4.87 (SD 7.4), and mean length of hospital stay was 8.5 days (SD 11.3). The main causes of hospitalization were mental disorders and diseases of the digestive system, as well as accidents or violence. Among those alcoholics alive after 1 year of follow-up, a significantly increased risk of dying in the following years could be predicted by early hospitalization in the 12 months preceding (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.15 to 2.60) or following (HR 3.59; 95% CI 2.31 to 5.61) enrollment in the cohort. CONCLUSIONS: Our results confirm the association of AUDs with several serious medical conditions. This fact may be responsible for a high impact on health resource utilization and high social costs. Early hospitalization significantly predicts vital status at 5 years.

Dietary and lifestyle determinants of malondialdehyde DNA adducts in a representative sample of the Florence City population.

Malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, is a mutagenic and carcinogenic compound that can react with DNA to form several types of DNA adducts including the deoxyguanosine adduct (M1dG). The aim of this cross-sectional study was to evaluate the association between individual dietary and lifestyle habits and M1dG levels, measured in peripheral leukocytes in a large representative sample of the general population of Florence City (Italy). Selected anthropometric measurements, detailed information on dietary and lifestyle habits and blood samples were available for 313 adults of the Florence City Sample enrolled in the frame of European Prospective Investigation into Cancer and nutrition (EPIC) study. A multivariate regression analysis adjusted for selected individual characteristics possibly related to M1dG levels (sex, age, BMI, smoke, physical activity level, education level, total caloric intake and a Mediterranean dietary score) was performed to estimate the association between these parameters and M1dG levels. M1dG levels were significantly higher in women (P = 0.014) and lower in moderately active or active subjects (P = 0.037).We also found a significant inverse association with the Modified Mediterranean dietary score (P for trend = 0.049), particularly evident for the highest categories of adherence. Our results indicate that M1dG levels can be modulated by selected individual characteristics such as gender, physical activity and a Mediterranean dietary pattern.

Surface imaging, portal imaging, and skin marker set-up vs. CBCT for radiotherapy of the thorax and pelvis.

AIM: The aim of this study was to compare surface imaging, portal imaging, and skin marker set-up in radiotherapy of thoracic and pelvic regions, using cone beam computed tomography (CBCT) data as the gold standard. PATIENTS AND METHODS: Twenty patients were included in this study. CBCT, surface acquisition (SA), and two orthogonal portal images (PI) were acquired during the first four treatment sessions. Patient set-up corrections, obtained by registering the planning CT with CBCT, were used as the gold standard. Registration results of the PI and SA were evaluated and compared with those obtained with CBCT. The advantage derived from using SA or PI verification systems over a skin marker set-up was also quantified. RESULTS: A statistically significant difference between PI and SA (in favour of PI) was observed in seven patients undergoing treatment of the pelvic region and in two patients undergoing treatment of the thoracic region. The use of SA or PI, compared with a skin marker set-up, improved patient positioning in 50% and 57% of the thoracic fractions, respectively. For pelvic fractions, the use of PI was beneficial in 73% of the cases, while the use of SA was beneficial in only 45%. Patient positioning worsened with SA, particularly along longitudinal and vertical directions. CONCLUSION: PI yielded more accurate registration results than SA for both pelvic and thoracic fractions. Compared with the skin marker set-up, PI performances were superior to SA for pelvic fractions while comparable results were obtained for thoracic fractions.

Plasma clusterin as a candidate pre-diagnosis marker of colorectal cancer risk in the Florence cohort of the European Prospective Investigation into Cancer and Nutrition: a pilot study.

BACKGROUND: Colorectal cancer is one of the major causes of cancer mortality world-wide. Prevention would improve if at-risk subjects could be identified. The aim of this study was to characterise plasma protein biomarkers associated with the risk of colorectal cancer in samples collected prospectively, before the disease diagnosis. METHODS: After an exploratory study on the comprehensive plasma proteome analysis by liquid chromatography-tandem mass spectrometry from ten colorectal cancer cases enrolled at diagnosis, and ten matched controls (Phase 1), a similar preliminary study was performed on prospective plasma samples from ten colorectal cancer cases, enrolled years before disease development, and ten matched controls identified in a nested case-control study within the Florence cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study (Phase 2); in Phase 3 the validation of the candidate biomarkers by targeted proteomics on 48 colorectal cancer cases and 48 matched controls from the Florence-EPIC cohort, and the evaluation of the disease risk were performed. RESULTS: Systems biology tools indicated that both in the Phase 1 and Phase 2 studies circulating protein levels differing in cases more than 1.5 times from controls, were involved in inflammation and/or immune response. Eight proteins including apolipoprotein C-II, complement C4-B, complement component C9, clusterin, alpha-2-HS-glycoprotein, mannan-binding lectin serine-protease, mannose-binding protein C, and N-acetylmuramoyl-L-alanine amidase were selected as promising candidate biomarkers. Targeted proteomics of the selected proteins in the EPIC samples showed significantly higher clusterin levels in cases than controls, but only in men (mean ± SD, 1.98 ± 0.46 and 1.61 ± 0.43 nmol/mL respectively, Mann-Whitney U, two-tailed P = 0.0173). The remaining proteins were unchanged. Using multivariate logistic models a significant positive association emerged for clusterin, with an 80% increase in the colorectal cancer risk with protein's unit increase, but only in men. CONCLUSIONS: The results show that plasma proteins can be altered years before colorectal cancer detection. The high circulating clusterin in pre-diagnostic samples suggests this biomarker can improve the identification of people at risk of colorectal cancer and might help in designing preventive interventions.

[Alcohol consumption and epithelial cancer risk in the EPIC-Italy cohort]. / Consumo di bevande alcoliche e rischio di tumori epiteliali nella coorte EPIC-Italia.

OBJECTIVES: to evaluate the association between baseline and lifetime alcohol consumption and the risk of epithelial cancer (all types) in the Italian cohort of the European Prospective Investigation into Cancer and nutrition (EPIC) study. DESIGN: prospective study carried out in a large Italian population. SETTING AND PARTICIPANTS: detailed information on the consumption of alcoholic beverages at baseline and over lifetime collected at enrolment into the EPIC study (1993-1998) by standardised questionnaires for 44,477 healthy adults. MAIN OUTCOMES MEASURES: 2,640 incident epithelial cancers identified during a mean follow-up of 11.4 years. Multivariate Cox proportional hazard models adjusted for several potential confounders were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). RESULTS: lifetime alcohol consumption (p for trend =0.005) was associated with epithelial cancer risk in the whole cohort. This effect was more evident in women (p =0.049) and in current smokers (p =0.012). Alcohol consumption at baseline was associated with the epithelial cancer risk in women (p for trend =0.01) and current smokers (p for trend =0.02). A significant interaction between alcohol consumption and smoke duration (p =0.015 for baseline; p =0.006 for lifetime) was identified. CONCLUSIONS: in this large Italian population, alcohol consumption, particularly lifetime, is a significant risk factor for the development of epithelial cancers. This effect appears to be modulated by smoking habits.

New frontiers in sport training: genetics and artistic gymnastics.

The increasing understanding of the genetic influences in sport has prompted an association study between the athletic performances and the polymorphisms of the angiotensin-converting enzyme (ACE), the α-actinin-3 (ACTN3), and the vitamin D receptor genes. The details of these gene polymorphisms can provide useful information to improve and plan new modern training programs for elite athletes. Eighty Italian male high level gymnasts were trained and tested for gymnastic-specific exercises and tested in all the men's artistic gymnastic apparatus (floor, pommel horse, rings, vault, parallel bars, and horizontal bar), and then genotyped. The training parameters of volume, intensity, and density of each gymnast were periodically measured during the season in each apparatus from the tests performed, and the seasonal average values were calculated. Gene polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism assay and studied in association with the performance results. The performances of ACE II gymnasts were significantly lower than that of the ACE ID/DD gymnasts in the apparatus expressing power features, confirming the predisposition of these athletes toward power-oriented sport. Gymnasts with ACTN3 RR/RX genotypes did not show a predisposition to the power-oriented apparatus, having worse performances compared with that of the ACTN3 XX gymnasts. Similarly, gymnasts with ACE II + ACTN3 RR/RX combined genotypes showed lower performances in comparison with that of the other gymnasts. Vitamin D receptor polymorphisms showed no significant association with the athletic performances. Because ACE insertion/deletion (I/D) and ACTN3 R577X polymorphisms heavily affect the physical performance of elite male gymnasts, the Italian Gymnastic Federation trainers have started to customize the current high-level training programs.

Atypical and malignant meningioma: outcome and prognostic factors in 68 irradiated patients.

Meningiomas account for up to 20 % of all primary intracranial neoplasms; although the majority of these have a benign course, as many as 5-10 % can display more aggressive behavior and a higher incidence of disease progression. The benefit of immediate adjuvant radiotherapy is still being debated for atypical and malignant meningiomas. This study aimed to retrospectively assess prognostic factors and outcome in 68 patients with atypical and malignant meningiomas. Sixty-eight meningioma patients were treated with radiotherapy after initial resection or for recurrence, between January 1993 and December 2011. Surgery was macroscopically complete in 80 % of the patients; histology was atypical and malignant in 51 patients and 17 patients, respectively. Mean dose of radiotherapy was 54.6 Gy. Fifty-six percent of all patients received radiotherapy after surgical resection, 26 % at the first relapse, and 18 % at the second relapse. Median follow-up was 6.7 years, (range 1.5-19.9 years). The 5- and 10-year actuarial overall survival (OS) rates were 74.1 and 45.6 %, respectively. At univariate analysis age >60 years, radiotherapy dose >52 Gy showed statistical significance, (p = 0.04 and p = 0.03, respectively). At the multivariate analysis radiotherapy dose >52 Gy maintained the statistical significance, (p = 0.037). OS of patients treated with radiotherapy at diagnosis was longer than the survival of patients treated with salvage radiotherapy; however this difference did not reach statistical significance when tested for the entire series or for the subgroups of grade 2 and grade 3 patients. The 5- and 10-year disease-free survival (DFS) rates were 76.5 and 69.5 %, respectively, and were significantly influenced by size >5 cm (p = 0.04) and grading (p = 0.003) on univariate analysis. At multivariate analysis, size and grading both remained significant prognostic factors, p = 0.044 and p = 0.0006, respectively. Grade ≤ 2 acute side effects were seen during radiotherapy treatment in 16 % of the patients, with no ≥ grade 3 acute toxicity, based on the Common Terminology Criteria for Adverse Events. In this mono-institutional retrospective study, age and radiotherapy dose were associated with a longer OS, while preoperative size and grading of the tumor influenced DFS. Although there were some advantages in terms of OS for patients treated with postoperative radiotherapy, the benefit did not reach the significance. Multicenter prospective studies are necessary to clarify the management and the correct timing of radiotherapy in such a rare disease.

General and cancer mortality in a large cohort of Italian alcoholics.

BACKGROUND: The consumption of alcohol is an underappreciated risk factor for a wide range of conditions. Overall, it is associated with high mortality rates and causes approximately 4% of all deaths worldwide. This study aimed to evaluate the general and cancer mortality in a cohort of subjects with alcohol addiction residing in Tuscany (Central Italy). METHODS: Overall, 2,272 alcoholics (1,467 men and 805 women; mean age at first examination 43.8 years ± 13.0), treated at the Alcohol Centre of Florence in the period April 1985 to September 2001, were followed until the end of the study period (median follow-up: 9.6 years). A total of 21,855 person-years were available for analyses. Expected deaths were estimated by using age, sex, and calendar-specific regional mortality rates. Standardized mortality ratios (SMR) and 95% confidence intervals (CI) were calculated. RESULTS: Six hundred and thirty-six of the 2,272 patients (28.0%) died, yielding an SMR of 5.0 (95% CI: 4.6 to 5.4). The alcoholics had significantly elevated mortality risk from all malignant cancers (SMR = 3.8, 95% CI: 3.3 to 4.4) and a series of specific diseases (infections: SMR = 10.1, 95% CI: 4.8 to 21.1; diabetes: SMR = 3.6, 95% CI: 1.9 to 6.7; immunological system, including AIDS: SMR = 8.1, 95% CI: 4.1 to 16.2; nervous system: SMR = 3.5, 95% CI: 1.9 to 6.4; cardiovascular system: SMR = 2.4, 95% CI: 2.0 to 2.9; respiratory system: SMR = 5.8, 95% CI: 4.2 to 8.0; digestive system: SMR = 26.4, 95% CI: 22.6 to 30.8, including liver cirrhosis (SMR = 40.0, 95% CI: 33.9 to 47.1); violent causes: SMR = 6.6, 95% CI: 5.0 to 8.6). Among malignant cancers, the highest SMRs were found for cancers of the pharynx (SMR = 22.8, 95% CI: 9.5 to 54.8), oral cavity (SMR = 22.2, 95% CI: 13.2 to 37.6), liver (SMR = 13.5, 95% CI: 9.2 to 19.8), and larynx (SMR = 10.7, 95% CI: 5.8 to 19.9). Although women showed higher SMR in comparison with the general population of the area, their overall survival estimates during the follow-up were higher than those for male alcoholics. CONCLUSIONS: This large series of Italian alcoholics showed a significant increase in total and cancer mortality in comparison with the general population, with female alcoholics reporting higher survival rates.

A phantom evaluation of Sentinel(™), a commercial laser/camera surface imaging system for patient setup verification in radiotherapy.

PURPOSE: The aim of this study is to investigate the performance of Sentinel(™), a patient setup verification device based on a laser/camera system, when used on rigid-body phantoms. METHODS: The Sentinel system consists of a scanner unit, containing the laser and the camera, and surface-matching registration software. For the registration procedure, both a computed tomography (CT) and a Sentinel image can be used as a reference. Tests were performed on phantoms using an Elekta Synergy(®) beam modulator Linac equipped with a cone beam CT (CBCT), a HexaPOD RT couch top, and an iViewGT portal imaging system. Experiments conducted in this study tested reproducibility of the Sentinel surface acquisition and of set-up procedure, accuracy in quantifying known phantom mispositioning, and compared Sentinel, CBCT, and portal imaging system performance. RESULTS: Reproducibility of surface acquisition and setup procedure was better than 0.5 mm and 0.5° and 1 mm and 0.4°, respectively. The system accuracy was better than 1 mm and 1° when a Sentinel image was used as reference. A global worsening of Sentinel performance was observed using as reference an external surface extracted from CT study. This effect is probably due to small differences in considered surfaces, caused by different imaging modalities. The results obtained by testing the system on rigid phantoms were comparable to those obtained using CBCT and better than those obtained with conventional portal imaging systems. CONCLUSIONS: The Sentinel setup verification device is a reproducible and consistent system able to detect misalignments with accuracy better than 1 mm and 1°. When tested on rigid body phantoms, Sentinel and CBCT performed similarly. When compared to portal imaging, both Sentinel and CBCT were more accurate.

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.

Angiotensin-converting enzyme/vitamin D receptor gene polymorphisms and bioelectrical impedance analysis in predicting athletic performances of Italian young soccer players.

We evaluated the association between 2 genetic polymorphisms known to be involved in fitness and performance, and anthropometric features, body composition, and athletic performances in young male soccer players with the goal of identifying genetic profiles that can be used to achieve maximal results from training. One hundred twenty-five medium-high-level male soccer players were genotyped for angiotensin-converting enzyme (ACE) I/D, and vitamin D receptor (VDR) FokI gene polymorphisms and scored for anthropometric measurements, body composition, and athletic performance. Body mass index, fat mass, fat-free mass, resistance, reactance, impedance, phase angle (PA), and body cell mass were measured. Athletic performance was evaluated by squat jump, countermovement jump (CMJ), 2-kg medicine ball throw, 10- and 20-m sprint time. We observed that the homozygous ff genotype of the VDR gene was significantly more represented in young soccer players than in a matched sedentary population. Values of reactance and PA were differently distributed in ACE and VDR genotypes with high mean values in subjects with DD (ACE) and FF (VDR) genotypes. No correlation was observed between ACE or VDR genotypes and 2-kg medicine ball throw, 10- and 20-m sprint times. The ID genotype of ACE was associated with the best performances in squat jump and CMJ. Our results suggest that determination of ACE and VDR genotypes might help select those young athletes harboring the most favorable genetic potential to succeed in soccer.

Radical retropubic prostatectomy for prostate cancer with microscopic bladder neck involvement: survival and prognostic implications.

OBJECTIVE: To report the oncological outcome of 106 patients who had locally advanced prostate cancer with microscopic bladder neck invasion, identified in a series of 1129 patients surgically treated with retropubic radical prostatectomy over a 12-year period. PATIENTS AND METHODS: All specimens were reviewed. Microscopic bladder neck invasion was defined as the presence of neoplastic cells within the smooth muscle bundles of the bladder neck, with no accompanying prostatic glandular tissue on the corresponding slide. Survival was analysed for different subgroups in relation to several variables. RESULTS: The follow-up (median 7.2 years, mean 6.68, range 0.3-14) was available for 106 patients with microscopic bladder neck invasion. Seminal vesicle invasion was present in 69.8% of the cases, lymph node involvement in 29.2%, apex infiltration in 31.8%, and positive surgical margins in 23.6%. Biochemical progression occurred in 61 (57.5%) patients, and 25 of them died from cancer. The mean (sd) biochemical progression-free survival was 0.68 (0.05), 0.59 (0.05), 0.40 (0.05) and 0.38 (0.05) at 1, 2, 5 and 10 years, respectively. Age, Gleason score and lymph node invasion were independent prognostic factors on multivariate analysis. Overall and cancer-specific survival rates were 0.75 (0.04) and 0.80 (0.04) at 5 years and 0.57 (0.04) and 0.75 (0.04) at 10 years, respectively. Univariate analysis showed that seminal vesicle invasion, lymph node involvement and surgical Gleason score > or =8 significantly increased the risk of death. On multivariate analysis only the surgical Gleason score had an independent prognostic role with regard to overall survival (P = 0.01; odds ratio 2.82, 95% confidence interval 1.2-6.4) and cancer-specific survival (P < 0.001; 8.6, 2.5-28.8). CONCLUSIONS: In this series, overall and cancer-specific survival rates were comparable to those reported for surgically treated cT3 prostate cancers. The lack of need for external urinary diversion during the entire follow-up significantly contributed to the patients' quality of life.

Accuracy of iView and PIPSpro registration software.

In radiotherapy, treatment portal images and digitally reconstructed radiographs (DRRs) are used to monitor patient setup during clinical routine. The output of the registration between the portal image and the reference DRR indicates the patient displacement. If the registration is not reliable, the patient positioning will not be accurate. The aim of this work is to assess the intrinsic and the global accuracy of iView and PIPSpro, two widely used registration software programs that implement a manual and a semiautomatic approach, respectively. The intrinsic accuracy was tested using a computer generated phantom, while the overall accuracy was evaluated registering the portal images and the DRRs of an Alderson RANDO phantom. For DRRs, four treatment planning systems (TPS) and three CT studies with different slice thicknesses were considered.This study demonstrates that the intrinsic accuracy of iView and PIPSpro were within 1 pixel and 1°. Using a DRR extracted from a 2 mm CT study, the overall accuracy of both methods was about 2 mm and 1°. When thicker CT slices are considered, the global accuracy of both methods worsens, and differences larger than 1.5° between the rotation parameters estimated with iView and PIPSpro are evident. The results obtained with iView and PIPSpro were nearly equivalent.

Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms.

BACKGROUND & AIMS: The Helicobacter pylori gene cagA and s1 or m1 forms of vacA are more common in disease-associated strains. Recently, forms of cagA encoding multiple type C EPIYA segments (which increase phosphorylation-dependent CagA activity) and a new type i1 "intermediate region" polymorphism in vacA (which confers toxicity) have been described. We assessed the association of new and established cagA and vacA polymorphisms with disease. METHODS: We studied 203 H pylori-infected subjects (53 gastric cancer [GC], 52 peptic ulcer [PU], and 98 gastritis). vacA signal, mid and intermediate region polymorphisms, cagA presence, and EPIYA-C segment number were analyzed by polymerase chain reaction. RESULTS: cagA-positive strains were significantly associated with GC and PU (P < .001 and P < .05). GC risk was further associated with the number of cagA EPIYA-C segments (odds ratio [OR] = 7.37, 95% confidence interval [CI] = 1.98-27.48 for 1 EPIYA-C segment; OR = 32.5, 95% CI = 8.41-125.58 for 2 or more EPIYA-C segments). Increasing number of EPIYA-C segments also increased the risk of intestinal metaplasia. Type s1 and i1 vacA alleles were also associated with GC and type i1 vacA with PU (OR = 2.58, 95% CI = 1.19-5.61), including a significant association with duodenal ulcer. In multivariate analysis, the associations of cagA EPIYA-C segment number with GC and intestinal metaplasia as well as vacA i1 type association with PU remained. CONCLUSIONS: We confirmed the associations of cagA and vacA polymorphisms with disease but now define their most important features. For cancer risk, among Western strains, the most important factor is the number of cagA EPIYA-C segment. For PU risk, it is the intermediate region type of vacA.

Anthropometric and dietary determinants of blood pressure in over 7000 Mediterranean women: the European Prospective Investigation into Cancer and Nutrition-Florence cohort.

BACKGROUND: Anthropometric characteristics and dietary habits are widely recognized to influence blood pressure. We evaluated their role in a large series of Mediterranean adult women. METHODS: In Florence, in the European Prospective Investigation into Cancer and Nutrition, we recruited 10 083 women, aged 35-64 years. Detailed information on diet, lifestyle, physical activity, and medical history were collected. Anthropometric indices and systolic and diastolic blood pressures were measured at recruitment using standardized procedures. Overall, after excluding those women who reported a clinical diagnosis of hypertension and/or an antihypertensive treatment and those without measurements, 7601 women were available for analyses with an average systolic and diastolic blood pressure value of 123.2+/-16.0 and 78.7+/-9.4 mmHg, respectively. RESULTS: Multivariate regression models showed that body mass index (P<0.0001) and waist circumference (>or=88 cm, P<0.0001), as well as processed meat, potatoes, and wine consumption, were directly associated with both systolic and diastolic values. In contrast, a high consumption of selected foods resulted inversely associated with systolic (total vegetables, yoghurt, and eggs), diastolic (olive oil) or both systolic and diastolic values (leafy vegetables, milk, coffee). Analyses performed on nutrients showed a positive association with alcohol and sodium intake, and an inverse one with potassium and micronutrients derived from fruits and vegetables. CONCLUSION: In this large series of women from Tuscany, Central Italy, we confirm the independent influence of anthropometric characteristics on blood pressure. The role of specific foods and nutrients in modulating blood pressure also emerged, suggesting a central role for lifestyle modifications in blood pressure control.

Association between the BRCA2 N372H variant and male breast cancer risk: a population-based case-control study in Tuscany, Central Italy.

BACKGROUND: Male breast cancer (MBC) is a rare disease and little is known about its aetiology. Germ-line mutations of BRCA2 and, at lower frequency, of BRCA1 are implicated in a relatively small proportion of MBC cases. Common polymorphic variants in BRCA1 and BRCA2 genes may represent breast cancer (BC) susceptibility alleles and could be associated with a modestly increased risk of MBC at population level. Considering the relevant role of BRCA2 in MBC, we investigated whether the BRCA2 N372H variant, representing the only common non-synonymous polymorphism in BRCA2, might modulate the risk of BC in male populations. METHODS: A case-control study was performed comparing a population-based series of 99 MBC cases, characterized for BRCA1 and BRCA2 mutations, with 261 male population controls, all residing in Tuscany, Central Italy. All MBC cases and controls were genotyped for the BRCA2 N372H allele by TaqMan allelic discrimination assays. To evaluate the genotype specific risk of the BRCA2 N372H variant, MBC carriers of germ-line BRCA1/2 mutations were excluded from the analyses. RESULTS: No association emerged in univariate and age-adjusted analyses. Age-specific analyses suggested an increased risk for the HH homozygous genotype in subjects younger than 60 years. A statistically significant interaction emerged between this genotype and age (p = 0.032). When analyses were restricted to MBC cases enrolled in the first 4 years following diagnosis, a recessive model showed a significantly increased risk of MBC in HH subjects younger than 60 years (OR = 5.63; 95% CI = 1.70;18.61). CONCLUSION: Overall, our findings, although based on a relatively small series, suggest that the BRCA2 HH homozygous genotype might be positively associated with an increased risk of MBC in men younger than 60 years.

Total and cancer mortality in a cohort of ulcerative colitis and Crohn's disease patients: The Florence inflammatory bowel disease study, 1978-2010.

BACKGROUND: There is no consensus on the leading causes of death among inflammatory bowel diseases (IBD) patients. AIM: We present the results of an extended follow-up of the population-based Florence IBD cohort, including 689 ulcerative colitis and 231 Crohn's disease patients. METHODS: The causes of death of cohort members were determined through linkage with the local mortality registry. We calculated standardized mortality ratios (SMR) and 95% confidence intervals (95%CI) by applying gender-, age- and calendar time-death rates to person-years at risk. RESULTS: Ulcerative colitis patients had overall mortality comparable to the general population (SMR 0.99, 95%CI 0.85-1.14), though being at increased risk of dying from Hodgkin's disease (SMR 11.74, 95%CI 2.94-46.94), rectal cancer (SMR 3.69, 95%CI 1.66-8.22) and Alzheimer's disease (2.40, 95%CI 1.00-5.76). Crohn's disease patients had an increased overall mortality (SMR 1.79, 95%CI 1.39-2.27) and were at higher risk of dying from cancer (SMR 2.57, 95%CI 1.28-5.13) and non-cancer diseases of the respiratory system (SMR 2.51, 95%CI 1.05-6.04), brain cancer (SMR 6.26, 95%CI 1.57-25.02) and non-cancer diseases of the genitourinary system (SMR 4.38, 95%CI 1.10-17.52). CONCLUSIONS: IBD patients should be offered counselling on risk reduction strategies, as much of their mortality excess is potentially avoidable.

The Florence city sample: dietary and life-style habits of a representative sample of adult residents. a comparison with the EPIC-Florence volunteers.

A representative sample of the general population residing in the city of Florence was invited to participate in the local section of the EPIC study with two major aims: i) to carry out a population-based survey on dietary and life-style habits in this urban area of Tuscany, Central Italy; ii) to compare these results with a large series of EPIC volunteers residing in the same municipality in order to evaluate the differences between the two groups. A random sample of 500 residents (250 women) aged 40-64 years, was invited to participate in the study; 362/500 (72.4%) accepted and followed the EPIC protocol. The distribution of selected individual characteristics (including measured weight and height) showed a high prevalence of being overweight in men (52.2%) and obesity in both sexes (17.4% in men and 12.5% in women). A dietary pattern characterized by a high consumption of red meat, processed meats, olive oil and wine emerged in both sexes; the consumption of vegetables and fresh fruit was approximately 200 and 300 g/day, respectively. The estimated mean intakes of macronutrients reflected this pattern, with a high mean intake of total fat and protein. The mean contribution to total caloric intake provided by fat was 30.9% and 33.6% in these randomly sampled men and women, respectively. The results were compared with those of 9,123 Florence residents aged 40-64 years and enrolled as EPIC volunteers. Current smokers and less educated subjects were less represented among male volunteers, who, in general, showed a healthier dietary pattern (more fresh fruit and less spirits). Female volunteers were taller and heavier and consumed more fresh fruit but also more beef and less carbohydrates. Other statistically significant differences emerged, but the absolute values of these differences were usually modest and the two groups appeared remarkably similar. Overall, our results suggest that the large EPIC-Florence cohort was not strictly selected and showed a total caloric intake and a range of dietary variability similar to that of the general population of the same area.

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.

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.