Right bundle branch block: Prevalence, incidence, and cardiovascular morbidity and mortality in the general population.

Background: Right bundle branch block (RBBB) is among the most common electrocardiographic abnormalities. Objectives: To establish the prevalence and incidence of RBBB in the general population without cardiovascular events (CVE) and whether RBBB increases cardiovascular morbidity and mortality compared with patients with a normal electrocardiogram (ECG). Methods: A historical study of two cohorts including 2981 patients from 29 primary health centres without baseline CVE. Cox (for CVE) and logistic (for cardiovascular factors) regression was used to assess their association with RBBB. Results: Of the patients (58% women; mean age 65.9), 92.2% had a normal ECG, 4.6% incomplete RBBB (iRBBB) and 3.2% complete RBBB (cRBBB). Mean follow-up was five years. Factors associated with appearance of cRBBB were male sex (HR = 3.8; 95%CI: 2.4-6.1) and age (HR = 1.05 per year; 95%CI: 1.03-1.08). In a univariate analysis, cRBBB was associated with an increase in all-cause mortality but only bifascicular block (BFB) was significant after adjusting for confounders. cRBBB tended to increase CVE but the results were not statistically significant. Presence of iRBBB was not associated with adverse outcomes. Patients with iRBBB who progressed to cRBBB showed a higher incidence of heart failure and chronic kidney disease. Conclusion: In this general population cohort with no CV disease, 8% had RBBB, with a higher prevalence among men and elderly patients. Although all-cause mortality and CVE tended to increase in the presence of cRBBB, only BFB showed a statistically significant association with cRBBB. Patients with iRBBB who progressed to cRBBB had a higher incidence of CVE. We detected no effect of iRBBB on morbidity and mortality.

Diagnosis of right bundle branch block: a concordance study.

BACKGROUND: Right bundle branch block is one of the most common electrocardiographic abnormalities. Most cases of right bundle branch block are detected in asymptomatic patients in primary care, so a correct interpretation of electrocardiograms (ECGs) at this level is necessary. The objective of this research is to determine the degree of concordance in the diagnosis of incomplete and complete right bundle branch block between four primary care researchers and a cardiologist. METHODS: The research design is a retrospective cohort study of patients over 18 years of ages of patients over 18 years of ages who underwent an ECG for any reason and were diagnosed with right bundle branch block by their physician. The physicians participating, 4 primary care researchers and a cardiologist were specialized in interpreting electrocardiographic records. The diagnosis of incomplete and complete right bundle branch block was recorded and other secondary variables were analysed. In case of diagnostic discordance between the researchers, the ECGs were reviewed by an expert cardiologist, who interpreted them, established the diagnosis and analysed the possible causes for the discrepancy. RESULTS: We studied 160 patients diagnosed with right bundle branch block by their general practise. The patients had a mean age of 64.8 years and 54% of them were men. The concordance in the diagnosis of incomplete right bundle branch block showed a Fleiss' kappa index (k) of 0.71 among the five researchers and of 0.85 among only the primary care researchers. The k for complete right bundle branch block was 0.93 among the five researchers and 0.96 among only the primary care researchers. CONCLUSION: The interobserver agreement in the diagnosis of right bundle branch block performed by physicians specialized in ECG interpretation (primary care physicians and a cardiologist) was very good. The variability was greater for the diagnosis of incomplete right bundle branch block.

Utility of a Liquid Formulation of Levo-thyroxine in Differentiated Thyroid Cancer Patients.

The goal of levo-thyroxine (L-T4) administration in differentiated thyroid cancer (DTC) is to suppress thyroid stimulating hormone (TSH) levels. The tolerability and efficacy of a new formulation of liquid L-T4 vs. the previous tablet formulation was evaluated in a cohort of 59 patients with cured DTC. The correlation between breakfast modality and therapy was also monitored. Hormonal and clinical evaluations were performed before and 70 days after patients were switched from tablet to liquid L-T4 formulation, without changes in daily dose. Breakfast habits were evaluated. The interval between L-T4 therapy and breakfast was recorded. Patient approval of L-T4 formulations was evaluated. 8% of patients dropped out owing to adverse events. The modality of L-T4 administration proved adequate under tablet and liquid formulation in 64% and 68% of patients who fully complied with the protocol. While significantly more patients found the tablet formulation more agreeable, at the end of the protocol subjective symptoms had diminished significantly and 73% requested to remain on the liquid formulation. No change in TSH, thyroid hormones or thyroglobulin was noted during the study. A balanced breakfast containing less than 4 g of alimentary fibre did not interfere with L-T4 therapy. Liquid L-T4 seems to be a valid alternative formulation in DTC patients, its initial dislike being outweighed by a significant reduction in subjective symptoms. Both tablet and liquid L-T4 therapy require monitoring over time. A continental breakfast containing less than 4 g of alimentary fibres seems to favour the absorption of L-T4, whether in tablet or liquid formulation.

Efficacy of sorafenib and impact on cardiac function in patients with thyroid cancer: a retrospective analysis.

PURPOSE: Sorafenib has recently been recognized as an important standard option for the management of patients with differentiated thyroid cancer. Although data concerning cardiac safety are available in pan-tumor studies, no data are available on its use in everyday clinical practice in patients with thyroid cancer. METHODS: In the off-label program of our institution, we enrolled 14 patients with different histological types of thyroid cancer suitable for treatment with sorafenib. Our aims were to evaluate cardiac safety factors-LVEF (left ventricular ejection fraction), heart rate and blood pressure-the cardiac markers NT-proBNP and troponin I, radiological response evaluated by CT and (18)FDG-PET (according to RECIST 1.1 criteria) and biomarker reduction (Eastern Cooperative Oncology Group Performance Status: ECOG PS) 0-2. RESULTS: Patients with ECOG PS 2 accounted for 36%. After starting sorafenib, many patients displayed reduced or stabilized metabolic activity in target lesions (clinical benefit = 44%), radiologic reduction or stabilization (74%) and decreased cancer markers (90%). Lung metastases displayed the largest reductions in size. Median overall survival (OS) was 7 months and median progression-free survival (PFS) was 3 months. No sign of cardiotoxicity was observed in almost all patients. LVEF was altered in two patients and proved symptomatic in one. CONCLUSIONS: Sorafenib seems to be effective in reducing disease progression in the early stages of treatment (3-6 months). Responses varied considerably according to the criteria investigated. Cardiac toxicities did not raise concerns and were in line with data reported in other malignancies. However, cardiac monitoring is recommended.

Estrategias para la detección de infección por virus de la hepatitis C en población general / Strategies for the detection of hepatitis C viral infection in the general population

Objetivo: Evaluar cual de las 3 estrategias ensayadas es más efectiva para detectar nuevos casos de infección por virus de la hepatitis C (VHC) en atención primaria. Métodos: Estudio observacional, prospectivo y multicéntrico. Se evaluaron 3 estrategias: Estrategia 1: carta explicativa dirigida a personas adultas adscritas a 2 equipos de atención primaria (EAP), invitándoles a realizar un examen serológico. Estrategia 2: colocación en los EAP de pósteres y dípticos explicativos, ofreciendo la posibilidad de realizar un examen analítico. Estrategia 3: revisar el resultado de anti-VHC en los pacientes con hipertransaminasemia detectada en los últimos 2 años mediante la historia electrónica y efectuar determinación del anti-VHC en los casos en quienes no se había determinado. Resultados: Participaron 598 personas (51% mujeres con una media de edad de 50,6±13 años). Con la estrategia 1 se captaron 238 personas (4,1% de participación), con la estrategia 2, 69 personas (0,3%) y con la estrategia 3, 291 pacientes (100%). La detección de VHC oculto fue de un caso en las estrategias 1 y 2, representando una prevalencia del 0,4 y 1,4%, respectivamente, y de 2 casos en la estrategia 3 lo que representa una prevalencia de 0,7%. Conclusiones La búsqueda activa de casos ocultos de infección por VHC ha sido poco efectiva con los métodos ensayados, atendiendo al coste y esfuerzo que comportan (AU)

Objective: To evaluate which of the three studied strategies is the most effective to detect new cases of Hepatitis C virus (HCV) infections in primary care. Methods: This is an observational, prospective, and multicentre study evaluating three strategies. Strategy 1: provide an explanatory letter to adults assigned to two primary care teams (PCTs), inviting them to have a blood test. Strategy 2: place posters and leaflets in PCTs advertising the possibility of laboratory tests. Strategy 3: reexamine HCV antibody test results in patients with hypertransaminasemia diagnosed within the last two years through electronic records, and determine anti-HCV status in undiagnosed cases. Results: There were a total 598 participants (51% female with an average age of 50.6±13 years). There were 238 people (4.1% of letters sent) in Strategy 1, 69 people (0.3% of potential participation) in Strategy 2, and 291 people (100% participation) from Strategy 3. One new case of HCV was found in both Strategy 1 and Strategy 2, representing a prevalence of 0.4 and 1.4%, respectively. Two new cases of HCV were found in Strategy 3, representing a prevalence of 0.7%. Conclusions: The three studied strategies for detecting new cases of HCV infection are ineffective, especially in regards to their cost and effort (AU)

Strategies for the detection of hepatitis C viral infection in the general population.

OBJECTIVE: To evaluate which of the three studied strategies is the most effective to detect new cases of Hepatitis C virus (HCV) infections in primary care. METHODS: This is an observational, prospective, and multicentre study evaluating three strategies. Strategy 1: provide an explanatory letter to adults assigned to two primary care teams (PCTs), inviting them to have a blood test. Strategy 2: place posters and leaflets in PCTs advertising the possibility of laboratory tests. Strategy 3: reexamine HCV antibody test results in patients with hypertransaminasemia diagnosed within the last two years through electronic records, and determine anti-HCV status in undiagnosed cases. RESULTS: There were a total 598 participants (51% female with an average age of 50.6 ± 13 years). There were 238 people (4.1% of letters sent) in Strategy 1, 69 people (0.3% of potential participation) in Strategy 2, and 291 people (100% participation) from Strategy 3. One new case of HCV was found in both Strategy 1 and Strategy 2, representing a prevalence of 0.4 and 1.4%, respectively. Two new cases of HCV were found in Strategy 3, representing a prevalence of 0.7%. CONCLUSIONS: The three studied strategies for detecting new cases of HCV infection are ineffective, especially in regards to their cost and effort.

Ankle-brachial index in screening for asymptomatic carotid and intracranial atherosclerosis.

OBJECTIVE: To evaluate usefulness of ankle-brachial index (ABI) in the screening for asymptomatic cervico-cerebral atherosclerosis (CCA) against traditional vascular risk assessment. METHODS: This study included a random population sample of 933 Caucasians without prior cardiovascular disease but with a moderate and high vascular risk (REGICOR score 5-9% and ≥ 10%). Presence and degree of CCA was evaluated by color-coded duplex and significant stenosis >50% (SCCA) confirmed by MRA. RESULTS: Prevalence of significant carotid and/or intracranial stenosis was 6% in the whole population, but increased up to 25% among those subjects with ABI ≤ 0.9 regardless of REGICOR score. Using REGICOR ≥ 10%, the likelihood ratio (LR) for the detection of SCCA was 1.8, while using ABI ≤ 0.90 the LR was 6.0. After multivariate regression analysis, low ABI was independently associated with SCCA whereas REGICOR score was not. Less than 40% of subjects with SCCA were taking antiplatelet drugs or statins at the moment of diagnosis. CONCLUSION: ABI emerged as a useful and simple tool in identifying asymptomatic SCCA in our population. This finding may be important for improving stroke primary prevention strategies.

The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study: prevalence and risk factors.

BACKGROUND AND PURPOSE: The ongoing population-based Barcelona-Asymptomatic Intracranial Atherosclerosis (Barcelona-AsIA) study is a prospective study that plans to investigate the natural history of asymptomatic intracranial atherosclerosis (AsIA) in a Caucasian-Mediterranean population, which remains unknown until now. The present study aims to determine the prevalence of AsIA and associated risk factors in the final study cohort. METHODS: Crossover, population-based study of a representative sample (randomly selected from our reference population) older than 50 with a moderate-high vascular risk assessed by the vascular equation REGICOR and prior history of neither stroke nor ischemic heart disease. Anthropometric, demographic, clinical data and blood samples were collected at baseline. All individuals underwent a complete extracranial and transcranial color-coded duplex (TCCD) examination. TCCD criteria were used to identify and classify the degree of intracranial stenoses. RESULTS: A total of 933 subjects (64% men, mean age 66.3 years) were included in the study. One or more intracranial stenoses were detected at baseline in 80 subjects (8.6%) of whom 31 (3.3%) had moderate-severe lesions. The higher the REGICOR scores the greater the prevalence of AsIA (6.6%, 10.2% and 25% for REGICOR scores 5-9, 10-14 and ≥15, p<0.001). Diabetes (OR 2.95; 95% CI (1.68-5.18); p<0.001), age (OR 1.05; 95% CI (1.02-1.08); p=0.001) and hypertension (OR 1.78; 95% CI (1.02-3.13); p=0.04) were independently associated with any degree of AsIA, while diabetes (OR 2.85; 95% CI (1.16-6.96); p=0.02) and age kept independently associated with moderate-severe AsIA. CONCLUSION: The prevalence of AsIA and moderate-severe AsIA in stroke-free Caucasians with a moderate-high vascular risk were 8.6% and 3.3% respectively. Diabetes and age were independently associated with moderate-severe AsIA.

[Vascular risk factors and cognitive performance in patients 50 to 65 years-old]. / Factores de riesgo vascular y rendimiento cognitivo en personas de 50 a 65 años.

INTRODUCTION: Vascular risk factors (VRF) have been related to cognitive deficits and an increased risk of dementia. Cognitive impairment is considered to be one of the earliest manifestations of cerebrovascular disease. In Spain there is a high prevalence of VRF, but also one of the lowest incidences of cerebrovascular disease in Europe. This is the first study that investigates the relationship between VRF and cognition in a Spanish sample. METHODS: A total of 90 people aged between 50-65 years with a low-to-moderate cardiovascular risk underwent a neuropsychological evaluation. None of them had a history of cardiovascular disease. The battery included tests assessing executive, attentional, mnesic, visuospatial and motor-speed/coordination functions. We used correlation and inter-groups comparison to relate VRF to multiple cognitive domains0120. RESULTS: Higher stroke risk was significantly related to a lowered profile in visuo-constructive functions and motor-speed/coordination. Moreover, the group with moderate cardiovascular risk showed a lower performance in visuoconstructive functions compared to the low-risk group. After statistical adjustment for age, sex and years of scholarship VRF were only related to motor-speed/coordination. CONCLUSIONS: In healthy, middle-aged adults, VRF are related with impairment in two cognitive domains. This effect is slight and tends to appear in people with moderate cardiovascular risk.

Factores de riesgo vascular y rendimiento cognitivo en personas de 50 a 65 años / Vascular risk factors and cognitive performance in patients 50 to 65 years-old

Introducción: Los factores de riesgo vascular (FRV) se han relacionado con déficit cognitivos e incremento del riesgo de demencia. De hecho, el deterioro cognitivo es considerado como una de las primeras manifestaciones de enfermedad cerebrovascular. En nuestro país se ha registrado una elevada prevalencia de FRV junto a una incidencia de ictus de las más bajas de Europa. Éste es el primer estudio con población española que investiga la relación entre los FRV y el rendimiento cognitivo en la edad adulta. Métodos: Se ha realizado evaluación neuropsicológica a 90 personas de 50-65 años de edad con riesgo cardiovascular bajo, leve y moderado, sin historia de enfermedad cardiovascular. Se les administró una batería de test sensible a funciones ejecutivas, atencionales, mnésicas, visuoconstuctivas y de velocidad/coordinación visuomotriz. Se han hecho análisis de correlación y comparación entre grupos para estudiar la relación entre los FRV y las diferentes funciones cognitivas.Resultados: Se observó una relación estadísticamente significativa entre un mayor riesgo vascular y un peor rendimiento en funciones visuoconstructivas y en velocidad/coordinación visuomotriz. Además, el grupo de riesgo moderado presentó un rendimiento significativamente inferior respecto al de riesgo bajo en funciones visuoconstructivas. Tras covariar por edad, sexo y años de escolaridad los FRV únicamente se relacionaron con velocidad/coordinación visuomotriz.Conclusiones: Los FRV en personas de mediana edad están relacionados con disminución del rendimiento en dos funciones cognitivas. La afectación es leve y tiende a evidenciarse en personas con un riesgo moderado (AU)

Introduction: Vascular risk factors (VRF) have been related to cognitive deficits and an increased risk of dementia. Cognitive impairment is considered to be one of the earliest manifestations of cerebrovascular disease. In Spain there is a high prevalence of VRF, but also one of the lowest incidences of cerebrovascular disease in Europe. This is the first study that investigates the relationship between VRF and cognition in a Spanish sample. Methods: A total of 90 people aged between 50-65 years with a low-to-moderate cardiovascular risk underwent a neuropsychological evaluation. None of them had a history of cardiovascular disease. The battery included tests assessing executive, attentional, mnesic, visuospatial and motor-speed/coordination functions. We used correlation and inter-groups comparison to relate VRF to multiple cognitive domains.Results: Higher stroke risk was significantly related to a lowered profile in visuo-constructive functions and motor-speed/coordination. Moreover, the group with moderate cardiovascular risk showed a lower performance in visuoconstructive functions compared to the low-risk group. After statistical adjustment for age, sex and years of scholarship VRF were only related to motor-speed/coordination. Conclusions: In healthy, middle-aged adults, VRF are related with impairment in two cognitive domains. This effect is slight and tends to appear in people with moderate cardiovascular risk (AU)

Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation.

Premature ejaculation (PE) is thought to be the most common male sexual dysfunction; however, the prevalence of lifelong (LL)-PE is relatively low. The aim of this study was to investigate the effects of on-demand vardenafil (10 mg) to modify the intravaginal ejaculatory latency time (IELT) in men with LL-PE without erectile dysfunction. Forty-two men (18-35 years) were enrolled in a 16-week, double-blind, placebo-controlled, cross-over study. Primary end point was the modification from baseline of IELT assessed by stopwatch technique; secondary end points were post-ejaculatory refractory time (PERT) and variations of scores at the Index of Premature Ejaculation questionnaire. The changes in geometric mean IELT were superior after taking vardenafil (0.6+/-0.3 vs 4.5+/-1.1 min, P<0.01), compared with placebo (0.7+/-0.3 vs 0.9+/-1.0 min, ns). PERT dropped significantly after vardenafil (16.7+/-2.0 vs 4.3+/-0.9 min, P<0.001), compared with placebo (15.3+/-2.2 vs 15.8+/-2.3 min). Patients who took vardenafil (vs placebo) reported significantly (P<0.01) increased ejaculatory control (6+/-2 vs 16+/-2), improved overall sexual satisfaction (7+/-2 vs 15+/-1) and distress (4+/-1 vs 8+/-1) scores, respectively. Multiple regression analysis (r(2)=0.86) for IELT by the number of attempts at sexual intercourse showed significant differences between the slopes of lines for placebo and vardenafil (P<0.0001). The most common adverse events for vardenafil (vs placebo) were headache (10 vs 3%), flushing (12 vs 0%) and dyspepsia (10 vs 0%), which tended to disappear over the time. In conclusion, in our study, vardenafil increased IELT and reduced PERT in men with LL-PE. Besides, improvements in confidence, perception of ejaculatory control and overall sexual satisfaction were reported.

Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST).

BACKGROUND: The relative contribution to gastric cancer (GC) risk of variants in genes that determine the inflammatory response remains mostly unknown and results from genotyping studies are inconsistent. PATIENTS AND METHODS: A nested case-control study within the prospective European Prospective Investigation into Cancer and Nutrition cohort was carried out, including 248 gastric adenocarcinomas and 770 matched controls. Twenty common polymorphisms at cytokine genes [interleukin (IL)1A, IL1B, IL1RN, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, lymphotoxin alpha and tumor necrosis factor (TNF)] were analyzed. Antibodies against Helicobacter pylori (Hp) and CagA were measured. RESULTS: IL1RN 2R/2R genotype [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.19-4.96] and allele IL1RN Ex5-35C were associated with an increased risk of Hp(+) non-cardia GC. IL8 -251AA genotype was associated with a decreased risk of Hp(+) non-cardia GC (OR 0.51; 95% CI 0.32-0.81), mainly of the intestinal type. These associations were not modified by CagA status. Carriers of IL1B -580C and TNF -487A alleles did not associate with an increased risk. A moderately increased risk of Hp(+) non-cardia GC for IL4R -29429T variant was observed (OR 1.74; 95% CI 1.15-2.63). CONCLUSION: This prospective study confirms the association of IL1RN polymorphisms with the risk of non-cardia GC and indicates that IL8 -251T>A may modify the risk for GC.

Factores etiológicos de la disnea al final de la vida / No disponible

Objetivos: analizar los factores etiológicos de la disnea en una población atendida por un Equipo de Cuidados Paliativos (ECP) de ámbito de actuación mixta (hospitalario y domiciliario). Metodología: estudio longitudinal retrospectivo de los pacientes seguidos por el ECP de Badajoz y que fueron éxitus en el año 2005. Se reclutaron 195 pacientes, y se registraron las siguientes variables: edad, sexo, presencia de disnea, enfermedad terminal, localización del cáncer, factores etiológicos de la disnea: a) cardiopulmonar: (directa/indirecta); b) enfermedad concomitante; y c) causas sistémicas, saturación basal de oxígeno (SatO2), niveles de hemoglobina (Hb), índice de Karnofsky. El análisis fue realizado con el paquete estadístico Stata9, empleándose modelos de regresión logística. Resultados: el 60% de los pacientes presentaron disnea. La edad media fue de 73 años, el 64% eran mujeres; la enfermedad oncológica representó el 88% de los casos, siendo el cáncer de pulmón (n = 39) la neoplasia más frecuente. El odds de presentar disnea en los pacientes con afectación cardiopulmonar directa (1) e indirecta (2), era superior a aquellos que no referían disnea (OR1 = 0,1 OR2 = 0,05, p = 0,0001). El odds de la etiología sistémica fue > al 50% en pacientes con disnea (p = 0,052). No se demostró una asociación significativa entre SatO2 baja y disnea (p = 0,12). Los niveles de Hb ( < 11 mg/dl) se asociaron con la presencia de disnea (OR = 0,09/p = 0,005). Conclusiones: la afectación cardiopulmonar fue el factor etiológico más frecuente. Parece existir una asociación entre la etiología sistémica y la disnea. Los pacientes con cifras inferiores de Hb, mostraron mayor probabilidad de padecer disnea

Objectives: to analyze the etiologic factors of dyspnea in a population treated by a palliative care support team with both in-hospital and home activities. Methodology: a retrospective longitudinal study of patients included in a palliative care program within Badajoz health area who died in 2005. In all, 195 patients were recruited and the following variables were studied: age, sex, % patients with dyspnea, type of terminal disease, cancer site, etiologic factors of dyspnea (1. Local heart and lung (direct/indirect). 2. Associated disease. 3. Systemic causes). Oxigen saturation, hemoglobin level, and Karnofsky index. The analysis was performed using the statistical Stata9 method and logistic regression models. Results: sixty percent of cases showed dyspnea. Mean age was 73 (64% women). Cancer represented 88% of all cases (lung cancer was most frequent). The “odds” of dyspnea in patients with cardiac and lung disease, both direct (1) and indirect (2), were higher than in patients without that etiology (OR1 = 0.1 OR2 = 0.05, p = 0.0001). The odds of systemic causes were > 50% in patients with dyspnea (p = 0.052). The association was not statistically significant between oxygen saturation and dyspnea (p = 0.12). Hemoglobin levels were statistically associated with dyspnea (OR: 0.09/p = 0.005). Conclusions: the presence of cardiac and lung disease was the most prevalent etiology. Systemic causes were also associated with dyspnea. Patients with lower hemoglobin levels were more likely to suffer from dyspnea

Consumption of cruciferous vegetables and glucosinolates in a Spanish adult population.

OBJECTIVE: To assess the intake of glucosinolates and cruciferous vegetables among Spanish adults. DESIGN: Cross-sectional analysis of a prospective cohort study. SETTING: The Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: We analysed data from 40 684 men and women aged 35-64 years from the EPIC-Spain cohort. The usual diet was assessed by means of the dietary history method, and glucosinolate intake was calculated using a published food composition database. RESULTS: The average intake of cruciferous vegetables was 11.3 g/day, accounting for about 5% of total vegetable consumption, whereas the daily intake of total glucosinolates was 6.5 mg, among which 35% were of indole type. The absolute intake of glucosinolates was in average higher in men than in women (6.8 vs 6.2 mg/day), whereas glucosinolate density per energy unit was higher in women's diet (3.4 vs 2.7 mg/4200 kJ). Northern regions consumed in average 36% more glucosinolates than Southern regions (7.3 vs 5.4 mg/day). There was a positive association of glucosinolate intake with body mass index, physical activity, educational level and an inverse relationship with alcohol consumption. CONCLUSIONS: Contrary to the pattern seen for total vegetable intake, our estimate of consumption of cruciferous vegetables, and hence of glucosinolates, is relatively low within Europe, which in turn is lower than in North America and several Asian populations.

Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions.

It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n=124), lung cancer (n=116) and myeloid leukemia (n=169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P<0.001, mean CVC of 6.60, P=0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C>T (mean prediction error of 22%, P<0.001, mean CVC consistency of 7.40, P<0.037). For leukemia, a 3-loci model including RAD52-2259C>T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P<0.001) and a maximum CVC of 4.40 (P=0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition.

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.

Validity of self reported diagnoses of cancer in a major Spanish prospective cohort study.

INTRODUCTION: This study aims to assess the validity of self reported diagnoses of cancer by persons recruited for the Spanish EPIC (European prospective investigation into cancer and nutrition) cohort study and to identify variables associated with correctly reporting a diagnosis of cancer. METHODS: 41 440 members of EPIC were asked at the time of recruitment whether they had been diagnosed with cancer and the year of diagnosis and site. The process of validating self reported diagnoses of cancer included comparison of the cohort database with the data from the population based cancer registries. Cancer diagnostic validity tests were calculated. The association between a correct report and certain sociodemographic, tumour related, or health related variables were analysed by logistic regression. RESULTS: The overall sensitivity of self reported diagnoses of cancer is low (57.5%; 95% CI: 51.9 to 63.0), the highest values being shown by persons with a higher level of education or with a family history of cancer and the lowest values by smokers. Breast and thyroid cancers are those with the highest diagnostic validity and uterus, bladder, and colon-rectum those with the lowest. In both sexes the variables showing a significant association with a correct report of cancer are: higher education level, number of previous pathologies, invasive tumour, and, in women, a history of gynaecological surgery. CONCLUSIONS: The overall sensitivity of self reported diagnoses of cancer is comparatively low and it is not recommended in epidemiological studies for identifying tumours. However, self reported diagnoses might be highly valid for certain tumour sites, malignant behaviour, and average to high levels of education.

Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study.

Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.

DNA repair polymorphisms and cancer risk in non-smokers in a cohort study.

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.