Risk of prostate cancer in the proximity of industrial installations: A multicase-control study in Spain (MCC-Spain).

BACKGROUND: Prostate cancer (PC) is the second most frequent tumor in men worldwide; however, its etiology remains largely unknown, with the exception of age and family history. The wide variability in incidence/mortality across countries suggests a certain role for environmental exposures that has not yet been clarified. OBJECTIVE: To evaluate the association between risk of PC (by clinical profile) and residential proximity to pollutant industrial installations (by industrial groups, groups of carcinogens, and specific pollutants released), within the context of a Spanish population-based multicase-control study of incident cancer (MCC-Spain). METHODS: This study included 1186 controls and 234 PC cases, frequency matched by age and province of residence. Distances from participants' residences to the 58 industries located in the study area were calculated and categorized into "near" (considering different limits between ≤1 km and ≤ 3 km) or "far" (>3 km). Odds ratios (ORs) and 95 % confidence intervals (95%CIs) were estimated using mixed and multinomial logistic regression models, adjusted for potential confounders and matching variables. RESULTS: No excess risk was detected near the overall industries, with ORs ranging from 0.66 (≤2 km) to 1.11 (≤1 km). However, positive associations (OR; 95%CI) were found, by industrial group, near (≤3 km) industries of ceramic (2.54; 1.28-5.07), food/beverage (2.18; 1.32-3.62), and disposal/recycling of animal waste (2.67; 1.12-6.37); and, by specific pollutant, near plants releasing fluorine (4.65; 1.45-14.91 at ≤1.5 km) and chlorine (5.21; 1.56-17.35 at ≤1 km). In contrast, inverse associations were detected near industries releasing ammonia, methane, dioxins+furans, polycyclic aromatic hydrocarbons, trichloroethylene, and vanadium to air. CONCLUSIONS: The results suggest no association between risk of PC and proximity to the overall industrial installations. However, some both positive and inverse associations were detected near certain industrial groups and industries emitting specific pollutants.

Total worker health® based Helicobacter pylori public health prevention strategy.

Purpose of review: This review aims to explore the public health approach for Helicobacter pylori Infection Prevention within the Total Worker Health (TWH) framework strategy. Recent findings: The review identifies certain occupations considered high-risk groups for H. pylori infection. It underscores primary, secondary, and tertiary public health preventive measures align with the TWH approach. Within this framework, the role of raising awareness, emphasizing infection control, worker hygiene, risk assessment, and ensuring healthcare accessibility is emphasized. The importance of early detection, treatment, eradication, and a TWH approach emerges as a central theme. The TWH approach offers a holistic perspective, intertwining occupation-related health risks with overall health and well being. Summary: Adopting the TWH approach, coupled with household-based infection control and eradication strategies, can significantly reduce H. pylori prevalence, fostering a healthier workforce and diminishing long-term healthcare costs. The review underscores the importance of recognizing H. pylori as an occupational disease. It calls for further research into the "one-health" perspective on H. pylori transmission dynamics.

Ambient air temperature exposure and foetal size and growth in three European birth cohorts.

INTRODUCTION: Ambient air temperature may affect birth outcomes adversely, but little is known about their impact on foetal growth throughout pregnancy. We evaluated the association between temperature exposure during pregnancy and foetal size and growth in three European birth cohorts. METHODS: We studied 23,408 pregnant women from the English Born in Bradford cohort, Dutch Generation R Study, and Spanish INMA Project. Using the UrbClimTM model, weekly ambient air temperature exposure at 100x100m resolution at the mothers' residences during pregnancy was calculated. Estimated foetal weight, head circumference, and femur length at mid and late pregnancy and weight, head circumference, and length at birth were converted into standard deviation scores (SDS). Foetal growth from mid to late pregnancy was calculated (grams or centimetres/week). Cohort/region-specific distributed lag non-linear models were combined using a random-effects meta-analysis and results presented in reference to the median percentile of temperature (14 °C). RESULTS: Weekly temperatures ranged from -5.6 (Bradford) to 30.3 °C (INMA-Sabadell). Cold and heat exposure during weeks 1-28 were associated with a smaller and larger head circumference in late pregnancy, respectively (e.g., for 9.5 °C: -1.6 SDS [95 %CI -2.0; -0.4] and for 20.0 °C: 1.8 SDS [0.7; 2.9]). A susceptibility period from weeks 1-7 was identified for cold exposure and a smaller head circumference at late pregnancy. Cold exposure was associated with a slower head circumference growth from mid to late pregnancy (for 5.5 °C: -0.1 cm/week [-0.2; -0.04]), with a susceptibility period from weeks 4-12. No associations that survived multiple testing correction were found for other foetal or any birth outcomes. CONCLUSIONS: Cumulative exposure to cold and heat during pregnancy was associated with changes in foetal head circumference throughout gestation, with susceptibility periods for cold during the first pregnancy trimester. No associations were found at birth, suggesting potential recovery. Future research should replicate this study across different climatic regions including varying temperature profiles.

Nitrogen dioxide exposure, attentional function, and working memory in children from 4 to 8 years: Periods of susceptibility from pregnancy to childhood.

BACKGROUND: Air pollution exposure during pregnancy and childhood has been linked to executive function impairment in children, however, very few studies have assessed these two exposure periods jointly to identify susceptible periods of exposure. We sought to identify potential periods of susceptibility of nitrogen dioxide (NO2) exposure from conception to childhood on attentional function and working memory in school-aged children. METHODS: Within the Spanish INMA Project, we estimated residential daily NO2 exposures during pregnancy and up to 6 years of childhood using land use regression models (n = 1,703). We assessed attentional function at 4-6 years and 6-8 years, using the Conners Kiddie Continuous Performance Test and the Attention Network Test, respectively, and working memory at 6-8 years, using the N-back task. We used distributed lag non-linear models to assess the periods of susceptibility of each outcome, adjusting for potential confounders and correcting for multiple testing. We also stratified all models by sex. RESULTS: Higher exposure to NO2 between 1.3 and 1.6 years of age was associated with higher hit reaction time standard error (HRT-SE) (0.14 ms (95 % CI 0.05; 0.22) per 10 µg/m3 increase in NO2) and between 1.5 and 2.2 years of age with more omission errors (1.02 (95 % CI 1.01; 1.03) of the attentional function test at 4-6 years. Higher exposure to NO2 between 0.3 and 2.2 years was associated with higher HRT-SE (10.61 ms (95 % CI 3.46; 17.75) at 6-8 years only in boys. We found no associations between exposure to NO2 and working memory at 6-8 years. CONCLUSION: Our findings suggest that NO2 exposure during the first two years of life is associated with poorer attentional function in children from 4 to 8 years of age, especially in boys. These findings highlight the importance of exploring long-term effects of traffic-related air pollution exposure in older age groups.

Pro-vegetarian dietary patterns and essential and heavy metal exposure in children of 4-5-years from the INfancia y medio Ambiente cohort (INMA).

Dietary patterns provide a comprehensive assessment of food consumption, including essential nutrients and potential exposure to environmental contaminants. While pro-vegetarian (PVG) dietary patterns have shown health benefits in adults, their effects on children are less well studied. This study aims to explore the association between children's adherence to the most common PVG dietary patterns and their exposure to metals, assessed through urine concentration. In our study, we included a population of 723 children aged 4-5-years from the INfancia y Medio Ambiente (INMA) cohort in Spain. We calculated three predefined PVG dietary patterns, namely general (gPVG), healthful (hPVG), and unhealthful (uPVG), using dietary information collected through a validated Food Frequency Questionnaire. Urinary concentrations of various essential and heavy metals (Co, Cu, Zn, Se, Mo, Pb, and Cd) were measured using mass spectrometry. Additionally, urinary arsenic speciation, including arsenobetaine (AsB), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), and inorganic arsenic (iAs), was measured. The sum of urinary MMA and iAs was used to assess iAs exposure. We estimated primary (PMI) and secondary iAs methylation (SMI) indices. To explore the association between PVG dietary patterns in quintiles and metal exposure, we utilized multiple-adjusted linear regression models and the quantile g-computation approach. Compared with the lowest quintile, participants in the highest quintile of gPVG showed a 22.7% lower urinary Co (95% confidence interval (CI): -38.7; -1.98) and a 12.6% lower Se (95%CI: -22.9; -1.00) concentrations. Second quintile of adherence to hPVG was associated with a 51.7% lower urinary iAs + MMA concentrations (95%CI: -74.3; -8.61). Second quintile of adherence to an uPVG was associated with a 13.6% lower Se levels (95%CI: -22.9; -2.95) while the third quintile to this pattern was associated with 17.5% lower Mo concentrations (95%CI: -29.5; -2.95). The fourth quintile of adherence to gPVG was associated with a 68.5% higher PMI and a 53.7% lower SMI. Our study showed that adherence to a gPVG dietary pattern in childhood may modestly reduce the intakes of some essential metals such as Co and Se. Further investigations are warranted to explore any potential health implications.

Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification.

BACKGROUND: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored. METHODS: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold. RESULTS: Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12-3.50, P-value = 4.13 × 10-15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99-2.49, P-value = 5.70 × 10-46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72-0.74). CONCLUSIONS: Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.

Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.

CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility.

Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen-metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke-exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers (OR = 0.88, 95% confidence interval = 0.85-0.91, P = 2.18 × 10-16), which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor helicase-like transcription factor. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis. SIGNIFICANCE: The causal pathway connecting CYP2A6 genetic variability and activity, cigarette consumption, and lung cancer susceptibility in smokers highlights the need for behavior modification interventions based on host susceptibility for cancer prevention.

La financiación de la industria alimentaria y la investigación epidemiológica sobre nutrición y salud / Food industry funding and epidemiologic research in public health nutrition

El interés de la industria alimentaria por financiar investigaciones en temas de nutrición y salud no se limita solo al avance científico. Algunas revisiones sistemáticas han puesto de manifiesto un sesgo en las conclusiones de los estudios que habían recibido financiación de la industria alimentaria, particularmente cuando comunicaban los efectos de las bebidas azucaradas. En este contexto, coincidiendo con la XXXIV Reunión Científica de la Sociedad Española de Epidemiología, el Grupo de Nutrición de esta sociedad organizó una mesa temática titulada Industria alimentaria e investigación epidemiológica para abordar el tema de la conveniencia o no de que la industria alimentaria financie directamente proyectos de investigación, y los posibles conflictos de intereses que pueden derivarse de esta financiación. Todos/as los/las participantes coincidieron en la necesidad de garantizar el rigor y la calidad necesarios en los estudios, y su realización de forma independiente de la financiación recibida, para evitar sesgos que lleven a una pérdida de credibilidad de los resultados de las investigaciones por los posibles conflictos de intereses. El Dr. Pérez-Farinós y la Dra. Romaguera coincidieron en que una forma de evitar conflictos de intereses era impedir que la industria financiara proyectos de investigación; la Dra. Marcos y el Prof. Martínez-González indicaron la conveniencia de establecer mecanismos para evitar que la financiación de la industria influya tanto en la distribución de fondos entre grupos e instituciones como en el análisis y los resultados de las investigaciones, para garantizar al máximo la independencia de los investigadores, así como su ética profesional (AU)

The interests of the food industry to fund nutrition and health research are not limited to promoting scientific advances. Recently, several systematic reviews conducted about the effect of sugar-sweetened beverages and health outcomes have shown some biased conclusions in studies that acknowledge industry sponsorship. In this context, the Nutrition Working Group of the Spanish Epidemiology Society presented a scientific session entitled Food industry and epidemiologic research at its annual meeting. In a round table, four experts in nutrition research presented their points of view about whether the food industry should fund nutrition-related research and the related potential conflicts of interest of the food industry. All the experts agreed not only on defending independence in nutritional epidemiology regarding the design, interpretation and conclusion of their studies but also on the crucial need for guaranteed scientific rigor, scientific quality of the results and measures to protect studies against potential biases related to the conflicts of interest of funding by the food industry. Drs Pérez-Farinós and Romaguera believe that the most effective way to prevent conflicts of interest would be not to allow the food industry to fund nutrition research; Drs Marcos and Martínez-González suggested the need to establish mechanisms and strategies to prevent the potential influences of the food industry in selecting researchers or institutional sponsorship and in the analysis and results of the studies, to ensure maximum independence for researchers, as well as their professional ethics (AU)

Efecto del empleo y de la carga doméstica en el desarrollo fetal y en la duración de la gestación en una cohorte de mujeres embarazadas / Effect of employment and domestic load on fetal development and length of gestation in a birth cohort study

Fundamentos: Los estudios publicados no son concluyentes sobre el impacto de determinadas exposiciones ocupacionales en el embarazo, evidenciando la necesidad de considerar el doble rol, profesional y familiar, de las mujeres. El objetivo del presente trabajo fue evaluar el efecto de la situación laboral y de la carga doméstica de trabajo en la duración de la gestación y en el desarrollo fetal. Métodos: Mediante modelos de regresión univariante y multivariante, se estudió la asociación entre partos pretérmino (PPT) (<37 semanas), recién nacidos con bajo peso a término (BPT) (<2500g) y pequeños para su edad gestacional (PEG) (

Background: Published studies are not conclusive on the impact of certain occupational exposures in pregnancy, stressing the need to consider the double role, professional and family, of women. The objective of this study is to evaluate the effect of employment and domestic load on the duration of pregnancy and fetal development. Methods: Using Univariate and Multivariate regression models, we studied the association of preterm deliveries (PPT) (<37 weeks), full term newborns with low weight (BPT) (<2500g) and small for their gestational age (PEG) (<10th percentile) in weight, length and head circumference according to work situation (employment/non-employment) and domestic load (low/ medium/high) in 2506 women. The analyses were carried out using SPSS and R. Results: Women with medium domestic load have lower risk of PPT (OR=0.41, 95%CI:0.21-0.81), PEG in weight (OR=0.47, 95%CI:0.32-0.69), length (OR=0.57, 95%CI:0.39-0.83) and head circumference (OR=0.58, 95% CI:0.40-0.83) and with high load PEG in weight (OR=0.72, 95%CI:0.54-0.98) and head circumference (OR = 0.73, 95% CI:0.54-0.99). When analyzing employment situation and domestic load, women with medium domestic load have less risk of PPT (OR=0.29, 95%CI:0.14-0.58) than the absence of load or high domestic load. Conclusions: The results show a protective effect of the medium and high domestic load, reducing the probability of preterm birth and small for gestational age babies

Efecto del alcohol y sus metabolitos en el cáncer de pulmón: estudio CAPUA / Effect of alcohol and its metabolites in lung cancer: CAPUA study

Antecedentes y objetivo: El alcohol y sus metabolitos tienen un papel importante en la carcinogénesis, pudiendo estar este efecto modulado por polimorfismos en genes que codifican enzimas participantes en el metabolismo de alcohol y folato. Por ello, analizamos el efecto que podría tener el consumo de alcohol y los polimorfismos ADH1B Arg48His, ADH1B Arg370Cys, ADH1C Ile349Val, ALDH2 Glu540Lys, CYP2E1 RsaI, CYP2E1 DraI, CYP2E1 TaqI y MTHFR C677T en el riesgo de cáncer de pulmón. Pacientes y método: Se incluyeron 876 casos de cáncer de pulmón y 840 controles del estudio caso-control de base hospitalaria CAPUA. El genotipado de los SNP se realizó mediante la tecnología Sequenom MassArray (iPLEX GOLD). Resultados: Un consumo de alcohol de 0,1-9,9g/día disminuye el riesgo de cáncer de pulmón (ORajustada = 0,71; IC 95% 0,48-1,05), aunque no se alcanza la significación estadística. Un consumo de alcohol ≥ 30g/día y de tabaco ≥ 36 paquetes/año aumenta el riesgo de cáncer de pulmón (ORajustada = 26,68; IC 95% 12,69-56,10). Por otro lado, un consumo elevado de verduras (≥ 116,65g/día) o de frutas (≥ 233,13g/día) disminuye el riesgo de cáncer de pulmón con un consumo de alcohol de 0,1-9,9 g/día (ORajustada = 0,52; IC 95% 0,30-0,89; ORajustada = 0,58; IC 95% 0,33-1,03, respectivamente). Un consumo de alcohol de 10-29,9 g/día en individuos portadores del alelo ADH1B 48His aumenta el riesgo de cáncer de pulmón (ORajustada = 3,32; IC 95% 1,03-10,70). Conclusiones: El alcohol y polimorfismos en genes que participan en el metabolismo del alcohol y del folato están relacionados con el cáncer de pulmón (AU)

Background and objective: Alcohol and its metabolites play an important role in carcinogenesis. This effect could be modulated by polymorphisms in genes encoding enzymes involved in the metabolism of alcohol and folate. Therefore, we analyzed the effect of alcohol consumption and ADH1B Arg48His, ADH1B Arg370Cys, ADH1C Ile349Val, ALDH2 Glu540Lys, CYP2E1 RsaI, CYP2E1 DraI, CYP2E1 TaqI and MTHFR C677T polymorphisms on the risk of developing lung cancer. Patients and methods: We included 876 lung cancer cases and 840 controls of the CAPUA hospital-based case-control study. Genotyping was performed using the Sequenom MassArray (iPLEX GOLD) technology. Results: An alcohol consumption of 0.1-9.9g/day decreased lung cancer risk (ORadjusted = 0.71; 95% CI 0.48-1.05), although statistical significance was not achieved. A consumption ≥ 30g/day of alcohol and ≥ 36PY of tobacco increases lung cancer risk (ORadjusted = 26.68; 95% CI 12.69-56.10). On the other hand, a high consumption of vegetables (≥ 116.65g/day) and fruits (≥ 233.13g/day) decreases lung cancer risk with an alcohol consumption of 0.1-9.9g/day (ORadjusted = 0.52; 95% CI 0.30-0.89; ORadjusted = 0.58; 95% CI 0.33-1.03, respectively). An alcohol consumption of 10-29.9 g/day in ADH1B 48His allele-carriers increases lung cancer risk (ORadjusted = 3.32; 95% CI 1.03-10.70). Conclusions: Alcohol and polymorphisms in genes involved in the metabolism of alcohol and folate are related to the onset of lung cancer (AU)

Hipovitaminosis D y factores asociados a los 4 años en el norte de España / Hypovitaminosis D and associated factors in 4-year old children in northern Spain

INTRODUCCIÓN: La vitamina D es una prohormona esencial en la homeostasis del calcio y el fósforo. Estudios recientes muestran una elevada frecuencia de insuficiencia/deficiencia de vitamina D en población general a nivel mundial. Nuestro objetivo ha sido estimar la prevalencia de deficiencia e insuficiencia de vitamina D sérica [25(OH)D3] y examinar sus factores asociados en la infancia. MATERIAL Y MÉTODOS: Se ha estudiado a 283 niños participantes en la cohorte INMA-Asturias. Se determinó la 25(OH)D3 mediante cromatografía líquida de alta resolución. Se han estimado las prevalencias de deficiencia ([25(OH)D3 < 20 ng/ml) e insuficiencia (20-29,9 ng/ml) de vitamina D y se ha analizado la distribución de 25(OH)D3 por mes de extracción, ingesta y otros factores. RESULTADOS: La 25(OH)D3 media fue 20,1 ng/ml (rango 2,7-49,8). El 8,8% tenía 25(OH)D3 ≥ 30 ng/ml, el 38,5% entre 20-20,9 ng/ml y el 52,7% < 20 ng/ml. Se halló variación estacional con menores valores en invierno. No se encontró relación entre los niveles plasmáticos y la ingesta de vitamina D (mediana 2,7 g/día, rango 0,81-12,62), el tiempo al aire libre (mediana 3 h, rango: 0:21-6:55), el índice de masa corporal, ni el sexo, pero sí con los niveles de sus madres durante la gestación. CONCLUSIONES: Existe una elevada prevalencia de deficiencia/insuficiencia de vitamina D a los 4 años. La exposición solar podría no ser suficiente en nuestra región. Se deberían promover actividades al aire libre con una adecuada exposición a la luz solar. Dado el déficit de ingesta en la infancia, es necesario hacer recomendaciones de una alimentación variada rica en vitamina D en este periodo especialmente durante el invierno, valorando la necesidad de suplementar con vitamina D en los niños de riesgo

INTRODUCTION: Vitamin D is an essential prohormone in calcium and phosphorus homeostasis. Recent studies show a high frequency of insufficiency/deficiency of vitamin D in the general population worldwide. Our objective was to estimate the prevalence of circulating vitamin D [25(OH)D3] deficiency and insufficiency in children and examine the associated factors. MATERIAL AND METHODS: A total of 283 children, participants in the cohort INMA-Asturias, were studied. The 25(OH)D3 concentrations were quantified by high performance liquid chromatography. The prevalence of deficiency [25(OH)D3 < 20 ng/ml] and insufficiency [20-29.9 ng/ml] of vitamin D was estimated. Distribution of 25(OH)D3 for month of extraction of specimen, ingestion, and other factors were analysed. RESULTS: The mean 25(OH)D3 was 20.1 ng/ml (range 2.7-49.8), with 8.8% ≥ 30 ng/ml, 38.5% from 20-20.9 ng/ml, and 52.7% < 20 ng/ml. Seasonal variation was found, with lower values in winter. There was no relationship between plasma levels and intake of vitamin D (median 2.7 g/day, range 0.81-12.62), time outdoors (mean 3 hours, range: 0:21-6:55), or BMI or gender, but there was one found with the mother's levels during gestation. CONCLUSIONS: There is a high prevalence of vitamin D deficiency/insufficiency in children at 4 years. Solar exposure might not be enough in our region. Healthy children should be encouraged to follow adequate outdoor activities with associated sun exposure. Due the deficit of intake in childhood, recommendations are needed about a varied diet with vitamin D-containing foods in this age group, especially during the winter, and assessing the need of vitamin D supplementation in children at risk

Variaciones en el proceso de confirmación diagnóstica entre unidades de cribado poblacional de cáncer de mama / Variations in the diagnostic confirmation process between breast cancer mass screening units

Objetivo: Analizar las variaciones en el proceso de confirmación diagnóstica entre unidades de cribado, las variaciones en los resultados de cada episodio y la relación entre las tasas de las diferentes pruebas de confirmación diagnóstica y las de detección de lesiones. Método: Estudio observacional de las variaciones de las tasas estandarizadas de pruebas diagnósticas y de detección de lesiones, en 34 unidades de cribado de los programas poblacionales de detección precoz de cáncer de mama, de tres comunidades autónomas, en el periodo de 2002 a 2011. Resultados: Las razones de variación entre los percentiles 25-75 en las tasas de realización de pruebas diagnósticas oscilaron entre 1,68 (recitaciones) y 3,39 (punción-aspiración con aguja fina). En las tasas de detección de lesiones benignas, carcinoma ductal in situ y cáncer invasivo fueron, respectivamente, 2,79, 1,99 y 1,36. Se encontró una relación positiva entre las tasas de realización de pruebas y las tasas de detección en punción-aspiración con aguja fina y lesiones benignas (R2: 0,53), punción-aspiración con aguja fina y carcinoma invasivo (R2: 0, 28), biopsias cerradas y lesiones benignas (R2: 0,64), biopsias cerradas y carcinoma ductal in situ (R2: 0,61), y biopsias cerradas y carcinoma invasivo (R2: 0,48). Conclusiones: Se observaron variaciones en la realización de pruebas invasivas entre las unidades de detección precoz de cáncer de mama de mayor magnitud que las de detección de lesiones. Las unidades con más pruebas de punción-aspiración con aguja fina tienen mayores tasas de detección de lesiones benignas, y las que realizan más biopsias cerradas detectan más lesiones benignas y cáncer (AU)

Objective: To analyse variations in the diagnostic confirmation process between screening units, variations in the outcome of each episode and the relationship between the use of the different diagnostic confirmation tests and the lesion detection rate. Method: Observational study of variability of the standardised use of diagnostic and lesion detection tests in 34 breast cancer mass screening units participating in early-detection programmes in three Spanish regions from 2002-2011. Results: The diagnostic test variation ratio in percentiles 25-75 ranged from 1.68 (further appointments) to 3.39 (fine-needle aspiration). The variation ratio in detection rates of benign lesions, ductal carcinoma in situ and invasive cancer were 2.79, 1.99 and 1.36, respectively. A positive relationship between rates of testing and detection rates was found with fine-needle aspiration-benign lesions (R2: 0.53), fine-needle aspiration-invasive carcinoma (R2: 0 28), core biopsy-benign lesions (R2: 0.64), core biopsy-ductal carcinoma in situ (R2: 0.61) and core biopsy-invasive carcinoma (R2: 0.48). Conclusions: Variation in the use of invasive tests between the breast cancer screening units participating in early-detection programmes was found to be significantly higher than variations in lesion detection. Units which conducted more fine-needle aspiration tests had higher benign lesion detection rates, while units that conducted more core biopsies detected more benign lesions and cancer (AU)

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design / / Estudio multicaso-control de base poblacional de tumores comunes en España (MCC-Spain): razón y diseño del estudio

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain (AU)

Introducción: Presentamos el protocolo del estudio caso-control de base poblacional de 5 tumores comunes en España (MCC-Spain) que evalúa factores ambientales y genéticos. Métodos: Durante 2008-2013, se reclutaron 10.183 sujetos entre 20-85 años en 23 hospitales de 12 provincias españolas, incluyendo 1.115 casos de cáncer de próstata, 1.750 de mama, 2.171 colorrectal, 492 gastro-esofágicos, 554 de leucemia linfática crónica (LLC) y 4.101 controles poblacionales emparejados por frecuencia por edad, sexo y región de residencia. Las tasas de participación varían del 57% (cáncer de estómago) al 87% (casos de LLC) y del 30% al 77% en controles. Los participantes respondieron una entrevista personal informatizada sobre factores socio-demográficos, exposiciones ambientales, ocupación, medicación, estilos de vida, e historia médica personal y familiar. Además, cumplimentaron un cuestionario alimentario y realizaron entrevistas telefónicas. Se recogió sangre del 76% de los participantes y saliva para los casos de LLC y participantes que rechazaron la donación de sangre. En los casos, se recogió información clínica y se dispone de muestras de tumor fresco o parafinado a través de los biobancos de los hospitales. Se realizó el genotipado con un array de exoma suplementado con marcadores en pathways específicos. Se han planificado diversos análisis para evaluar la asociación de factores genéticos, personales y ambientales para cada tumor e identificar efectos pleiotrópicos. Discusión: Este estudio, desarrollado en el Consorcio de Investigación Biomédica de Epidemiología y Salud Pública (CIBERESP), es una iniciativa única para evaluar factores etiológicos de tumores comunes y promoverá la investigación en cáncer y prevención en España (AU)

Prevalencia de deficiencia e insuficiencia de vitamina D y factores asociados en mujeres embarazadas del norte de España / Prevalence of vitamin D deficiency and insuffiency and associated factors in pregnant women of northern Spain

Introducción y objetivos: El déficit de vitamina D durante el embarazo se ha relacionado con sucesos adversos durante la gestación y con el desarrollo infantil postnatal. En este estudio examinamos los niveles plasmáticos de vitamina D [25(OH)D3] y los factores asociados a su deficiencia e insuficiencia plasmática en embarazadas del norte de España. Material y método: Se han analizado los datos de 453 gestantes participantes en la cohorte INMA-Asturias a las que se determinó la 25(OH)D3 mediante cromatografía líquida de alta resolución. Se ha estimado la ingesta dietética de vitamina D mediante un cuestionario de frecuencia alimentaria validado. Se han estimado las prevalencias de deficiencia [25(OH)D3 <20ng/ml] e insuficiencia [20-29,9 ng/ml] de vitamina D y se ha analizado la distribución de 25(OH)D3 por mes de extracción y otros factores. Resultados: La concentración media de 25(OH)D3 fue 27,7 ng/ml (rango 6,4-69,5). Un 27,4% de gestantes presentaron niveles deficientes y un 35,3% insuficientes. Los niveles de 25(OH)D3 fueron mayores en los meses de verano (mediana 34,1 ng/ml). Hubo un mayor porcentaje de deficiencia en las gestantes con sobrepeso/obesidad (34,5%) y en las menores de 25 años (47,8%). La ingesta media diaria de vitamina D fue 5,48 µg/día (DT 2,82 rango 1,09-32,52). Durante los meses de octubre a mayo la ingesta se relacionó con los niveles de 25(OH)D3. Un 8,6% refirieron tomar suplementos de vitamina D. Conclusiones: Se ha detectado una elevada proporción de embarazadas con niveles de vitamina D considerados como deficientes o insuficientes, especialmente en los meses de octubre a mayo, en las gestantes con sobrepeso y obesidad y en las de menor edad (AU)

Background and objectives: The vitamin D deficiency during pregnancy has been associated with adverse events during pregnancy and the postnatal child development. In this study we examined plasma levels of vitamin D [25(OH)D3] and factors associated with plasma deficiency and insufficiency in pregnant women in northern Spain. Methods: We analyzed data from 453 pregnant women participating in the INMA-Asturias cohort in which was determined 25(OH)D3 by high resolution liquid chromatography. Dietary intake of vitamin D was estimated through a food frequency validated questionnaire. We estimated the prevalence of deficiency [25(OH)D3<20ng / ml] and insufficiency [20 to 29.9 ng / ml] of vitamin D and analyzed the distribution of 25(OH)D3 per month extraction and other factors. Results: The mean concentration of 25(OH)D3 was 27.7 ng/ml (range 6.4 to 69.5). 27.4% of pregnant women had deficient levels and 35.3% insufficient. Levels of 25(OH)D3 were higher in the summer months (median 34.1 ng/ml). There was a higher percentage of deficiency in pregnant women with overweight/obesity (34.5%) and under 25 years (47.8%). The average daily intake of vitamin D was 5.48 mg / day (SD 2.82 range 1.09 to 32.52). Intake during the months of October to May was associated with levels of 25(OH)D3. 8.6% reported taking supplements of vitamin D. Conclusions: We detected a high proportion of pregnant women with deficient or insufficient vitamin D levels, especially in the months of October to May, in pregnant women with overweight and obesity, and the youngest (AU)

Compliance of nutritional recommendations of spanish pregnant women according to sociodemographic and lifestyle characteristics: a cohort study / Cumplimiento de las recomendaciones nutricionales de mujeres embarazadas en España en relación a sus características sociodemográficas: estudio de una cohorte

Objective: To assess nutrient intakes and compliance with nutritional recommendations in pregnant women according to selected sociodemographic characteristics and lifestyles. Methods: Cross-sectional study based on data from Spanish INMA cohort which recruited 2,585 pregnant women between 2003 and 2008 from four different regions of Spain. Sociodemographic information and anthropometry was collected and dietary intake was assessed through Food Frequency Questionnaires. The adequacy of food group intake was assessed considering current recommendations and from the Spanish Society of Nutrition. Moreover, intake of vitamin A, vitamin C and vitamin E, were compared with the Dietary Reference Intakes of the US Institute of Medicine. Results: Percentage of women that did not fulfil the recommendations for cereals and legumes (3-4 servings/ day) was 70.0%, for fruit intake (2-3 servings/day) it was 39.2%, for vegetables (2-4 servings/day) 47.3% and for dairy (3-4 servings/day) it was 51.6%. Intake of fruit and vegetables increased with age, educational degree and with physical activity (p<0.005). Also non-Spanish achieved better the recommendations. Percentage of pregnant women that did not fulfil the requirements (DRI) of vitamins A and C was 13.2 % and 16.2 respectively. More than 65% of the women did not met the recommended diary intake of vitamin E of 19 mg/day during the lactation period. Conclusions: Maternal age, education, having healthy habits, as well as country of origin are factors strongly associated with the composition of the diet. Sedentary women and those with a low education are at risk for low vitamin and antioxidant intake and non-optimal food choices during pregnancy (AU)

Objetivo: Estudiar las ingesta dietética y cumplimiento de las recomendaciones nutricionales de una población de mujeres embarazadas, de acuerdo a sus características sociodemográficas y hábitos de vida. Métodos: se trata de un estudio prospectivo basado en datos de la cohorte española INMA (Infancia y Medioambiente). Se han reclutado 2.585 mujeres embarazadas entre los años 2003 y 2008 en cuatro regiones diferentes de España. La ingesta dietética ha sido recogida mediante Cuestionarios de Frecuencia Alimentaria (CFA) y la información antropométrica, sociodemográfica y de estilos de vida a través de cuestionarios generales. La ingesta de grupos de alimentos y de vitaminas A, C y E y carotenoides fueron comparadas con las ingestas dietéticas de referencia de las guías Española y Americana. Resultados: El porcentaje de mujeres embarazadas que no cumplían las recomendaciones de cereales y legumbres (3-4 raciones /día) fue del 70 %, de frutas (2-3 raciones /día) el 39,2%, de verduras (2-4 raciones /día) fue del 47,3% y de lácteos (3-4 raciones /día) el 51,6%. La ingesta de frutas y verduras fue mayor en mujeres extranjeras y aumento con la edad, con el nivel de estudios y en mujeres con mayor actividad física (p<0.005). El porcentaje de mujeres embarazadas que no cumplieron los requerimientos (CDR) de vitaminas A y C fueron el 13,2% 16, 2% respectivamente. Más del 65% de las mujeres no cumplieron el mínimo de ingesta de vitamina E (19 mg/día) recomendado para mujeres embarazadas y en periodo de lactancia. Conclusiones: En este estudio se ha observado que factores como la edad, educación, tener hábitos de vida saludables así como el país de origen están fuertemente asociados a la composición de la dieta en las mujeres embarazadas. Mujeres sedentarias y con bajo nivel educativo tienen ingesta más bajas de vitaminas y antioxidantes procedentes de las frutas y verduras y por lo tanto más riesgo de llevar una dieta poco adecuada durante el embarazo (AU)

Incidencia de cáncer de mama en relación con la participación en un programa de cribado poblacional / Breast cancer incidence related with a population-based screening program

Objetivo: Comparar la incidencia acumulada de cáncer de mama, su evolución temporal y el estadio al diagnóstico entre mujeres participantes y no participantes en un programa poblacional de detección precoz. Métodos: Estudio de cohortes de incidencia de cáncer de mama en relación con la participación en un programa de cribado poblacional. La población de estudio fueron mujeres de la población diana del programa, y la fuente de información para los diagnósticos y estadios, el Registro poblacional de tumores. El período de análisis estuvo comprendido entre 1999 y 2010. Resultados: Los riesgos relativos de diagnóstico de cáncer invasivo, in situ y total de las participantes en el programa respecto a las no participantes fueron, respectivamente, 1,16 (intervalo de confianza del 95% [IC 95%]: 0,94-1,43), 2,98 (IC 95%: 1,16-7,62) y 1,22 (IC 95%: 0,99-1,49). El riesgo relativo de participantes frente a no participantes para diagnóstico en estadio I fue de 2,47 (IC 95%: 1,55-3,96); para T1 de 2,58 (IC 95%: 1,67-3,99) y para afectación ganglionar negativa de 2,11 (IC 95%: 1,38-3,23). La incidencia acumulada tiene 2 puntos de cambio en ambos grupos, con unos porcentajes de cambio anual de 92,3 (IC 95%: 81,6-103,5) en 1999-2001, de 18,2 (IC 95%: 16,1-20,3) en 2001-2005 y de 5,9 (IC 95%: 4,0-7,8) en el último período en participantes, y de 72,6 (IC 95%: 58,5-87,9) para 1999-2001, de 12,6 (IC 95%: 7,9-17,4) en 2001-2005 y de 8,6 (IC 95%: 6,5-10,6) en el último período en no participantes. Conclusiones: La participación en el programa de cribado de cáncer de mama analizado incrementa el riesgo de tener un diagnóstico de carcinoma in situ, mientras que no se incrementa el riesgo de cáncer invasivo. Por otra parte, los diagnósticos en este grupo se producen en estadios más precoces (AU)

Objective: To compare breast cancer cumulative incidence, time evolution and stage at diagnosis between participants and non-participant women in a population-based screening program. Methods: Cohort study of breast cancer incidence in relation to participation in a population screening program. The study population included women from the target population of the screening program. The source of information for diagnostics and stages was the population-based cancer registry. The analysis period was 1999-2010. Results: The Relative Risk for invasive, in situ, and total cancers diagnosed in participant women compared with non-participants were respectively 1.16 (0.94-1.43), 2.98 (1.16-7.62) and 1.22 (0.99-1.49). The Relative Risk for participants versus non-participants was 2.47 (1.55-3.96) for diagnosis at stage I, 2.58 (1.67-3.99) for T1 and 2.11 (1.38-3.23) for negative lymph node involvement. The cumulative incidence trend had two joint points in both arms, with an Annual Percent of Change of 92.3 (81.6-103.5) between 1999-2001, 18.2 (16.1-20.3) between 2001-2005 and 5.9 (4.0-7.8) for the last period in participants arm, and 72.6 (58.5-87.9) between 1999-2001, 12.6 (7.9-17.4) between 2001-2005, and 8.6 (6.5-10.6) in the last period in the non-participant arm. Conclusions: Participating in the breast cancer screening program analyzed increased the in situ cumulative cancer incidence, but not the invasive and total incidence. Diagnoses were earlier in the participant arm (AU)

Polimorfismos genéticos y riesgo de cáncer de pulmón / Genetic polymorphisms and lung cancer risk

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Estudio de la evolución de la exposición a plomo en la población infantil española en los últimos 20 años. ¿ Un ejemplo no reconocido de «salud en todas las políticas»? / Trend in lead exposure in the Spanish child population in the last 20 years. An unrecognized example of health in all policies?

Objetivo: Describir la evolución temporal de las concentraciones de plomo en el aire en España, desde antes de su prohibición como aditivo de la gasolina hasta la actualidad, así como estudiar la evolución de la carga corporal de plomo en la población infantil española. Métodos: Se obtuvieron las concentraciones medias anuales de plomo en el aire en diversas ciudades españolas, desde la década de 1980 hasta la actualidad. Se realizó una búsqueda bibliográfica con el fin de identificar estudios publicados sobre concentraciones de plomo en la población infantil española. Resultados: En general se observó una disminución de las concentraciones de plomo, de mayor magnitud entre 1991 y 1999. Esta evolución decreciente se asocia con una disminución de las concentraciones de plomo en la población infantil española, desde 1989 (año en que se publica el primer estudio sobre exposición infantil al plomo) hasta hoy. La disminución, tanto en el aire como en la población infantil, es muy probable que sea consecuencia de las medidas legislativas que han regulado la cantidad máxima de plomo en la gasolina, desde 1987 hasta su prohibición total en agosto de 2001. Conclusiones: Desde el punto de vista de la salud pública, la prohibición del uso de gasolina con plomo fue una acción que aumentó la protección de la salud de la población española (AU)

Objective: To describe the time trend in atmospheric lead concentrations in Spain, from before lead was banned as a gasoline additive to the present, and to determine the trend in lead body burden in the Spanish child population. Methods: We obtained the annual average for atmospheric lead levels in several Spanish cities from the 1980s to the present. A literature search was conducted to identify published studies on lead concentrations in populations of Spanish children. Results: Overall, atmospheric lead levels decreased, particularly between 1991 and 1999. This downward trend was related to a decrease in lead concentrations in Spanish children from 1989, the year in which the first study of childhood lead exposure was published, until the present. The decreased concentrations in both air and in children was most probably a result of legislative measures regulating the maximum amount of lead in gasoline in 1987 until a complete ban in August 2001. Conclusions: From a public health point of view, the banning of leaded gasoline has significantly increased health protection in the Spanish population (AU)

Nitrate and trace elements in municipal and bottled water in Spain / Nitrato y elementos traza en agua embotellada y municipal en España

Objectives: To describe levels of nitrate and trace elements in drinking water from the study areas of a multicase-control study of cancer in Spain (MCC-Spain). Methods: A total of 227 tap water samples were randomly collected from 67 municipalities in 11 provinces and the nine most frequently consumed bottled water brands were sampled to measure levels of nitrate, arsenic, nickel, chromium, cadmium, lead, selenium and zinc. Results: The median nitrate level was 4.2mg/l (range<1-29.0), with similar levels in rural and urban municipalities (p=0.86). Trace elements were unquantifiable in 94% of tap water samples. Differences between areas were significant for nitrate (p<0.001) and arsenic (p=0.03). Only nitrate was quantifiable in bottled water (range 2.3-15.6mg/l). Conclusions: Nitrate levels in municipal water differed between regions and were below the regulatory limit in all samples, including bottled water. Trace element levels were low and mainly unquantifiable in tap and bottled water (AU)

Objetivos: Determinar las concentraciones de nitrato y de elementos traza en el agua de consumo de las áreas del estudio Multicaso-Control de Cáncer en España (MCC-Spain). Métodos: Se tomaron al azar 227 muestras de agua municipal en 67 municipios de 11 provincias, y 9 muestras de las aguas embotelladas más consumidas, para cuantificar la cantidad presente de nitrato, arsénico, níquel, cromo, cadmio, plomo y zinc. Resultados: La mediana de las cifras de nitrato fue 4,2mg/l (rango<1-29,0), con similares resultados en municipios urbanos y rurales (p=0,86). Los elementos traza fueron incuantificables en el 94% de las muestras de agua municipal. Se observaron diferencias entre áreas para nitrato (p<0,001) y arsénico (p=0,03). Solo el nitrato fue cuantificable en el agua embotellada (rango 2,3-15,6mg/l). Conclusiones: La cantidad de nitrato en el agua municipal difiere entre regiones y es menor que el límite regulatorio en todas las muestras. Los elementos traza son mayormente incuantificables tanto en el agua municipal como en la embotellada (AU)