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El 'Atlas of Cancer Mortality in Portugal and Spain 2003–2012', muestra la distribución espacial de la mortalidad municipal por distintos tipos cáncer para el periodo 2003-2012. Ha sido desarrollado por la Unidad de Epidemiología del Cáncer y Ambiental del Centro Nacional de Epidemiología del ISCIII, que forma parte del CIBERESP, y por el Departamento de Epidemiología del Instituto Nacional De Saúde Doutor Ricardo Jorge de Portugal. El estudio de la distribución geográfica del riesgo de fallecer por cáncer es una de las herramientas que se usan en epidemiología para generar hipótesis sobre la posible implicación de factores ambientales en el origen de los tumores. This project is partially supported by research grant from the Spanish Health Research Fund (FIS) of the National Institute of Health Carlos III (ISCIII), Spain (Project PI17CIII/00040: “Spatial distribution of municipal cancer mortality in Spain (SICAMSA)” (“Distribución Espacial de la Mortalidad municipal por CÁncer en ESpaña (DEMOCAES)”). Introduction. Methods. Results: Oesophagus (ICD-10 C15) Stomach (ICD-10 C16) Colorectal (ICD-10 C18–C21) Pancreas (ICD-10 C25) Larynx (ICD-10 C32) Lung (ICD-10 C33–C34) Female Breast (ICD-10 C50) Prostate (ICD-10 C61) Bladder (ICD-10 C67) Leukaemia (ICD-10 C91–C95) References. Annexes: Annex I and Annex II No

We present a novel approach for the analysis of multivariate case-control georeferenced data using Bayesian inference in the context of disease mapping, where the spatial distribution of different types of cancers is analyzed. Extending other methodology in point pattern analysis, we propose a log-Gaussian Cox process for point pattern of cases and the controls, which accounts for risk factors, such as exposure to pollution sources, and includes a term to measure spatial residual variation. For each disease, its intensity is modeled on a baseline spatial effect (estimated from both controls and cases), a disease-specific spatial term and the effects on covariates that account for risk factors. By fitting these models the effect of the covariates on the set of cases can be assessed, and the residual spatial terms can be easily compared to detect areas of high risk not explained by the covariates. Three different types of effects to model exposure to pollution sources are considered. First of all, a fixed effect on the distance to the source. Next, smooth terms on the distance are used to model non-linear effects by means of a discrete random walk of order one and a Gaussian process in one dimension with a Mat\'ern covariance. Models are fit using the integrated nested Laplace approximation (INLA) so that the spatial terms are approximated using an approach based on solving Stochastic Partial Differential Equations (SPDE). Finally, this new framework is applied to a dataset of three different types of cancer and a set of controls from Alcal\'a de Henares (Madrid, Spain). Covariates available include the distance to several polluting industries and socioeconomic indicators. Our findings point to a possible risk increase due to the proximity to some of these industries.

Title and summary, also in English. El cáncer de mama es el tumor más frecuente en Europa. Según la Agencia Internacional de Investigación del Cáncer, en 2006 se diagnosticaron unos 429.900 casos nuevos de cáncer de mama en Europa, con una tasa estandarizada de incidencia de 110 casos por 100.000 mujeres. También es la localización más frecuente en mujeres españolas: supone casi la cuarta parte de los casos de cáncer femeninos, y su incidencia está aumentando entre un 2-3% anual. Entre las posibles causas de este incremento están los cambios en los patrones reproductivos y en los hábitos de vida y la introducción de la terapia hormonal sustitutiva. Nuestro país, con una tasa de incidencia estandarizada estimada de 93,6 casos por 100.000 mujeres-año para 2006, ocupa una posición intermedia entre los países de Europa occidental y los del este. Es también una importante causa de mortalidad femenina. En 2005 causó la muerte de 5.703 mujeres españolas, con una tasa de mortalidad estandarizada de 18,6 por 100.000 mujeres-año. Desde los años 90 la mortalidad por cáncer de mama está descendiendo debido al diagnóstico precoz por programas de cribado y a los avances terapéuticos. En España esta tendencia decreciente se observa a partir de 1993, con un descenso de un 2,4% anual.La supervivencia global en Europa a los 5 años es cercana al 79%, inferior a la observada en EEUU (90%), y ha aumentado en los últimos años. En España, se sitúa en un 83%, significativamente más alta que la media europea. Breast cancer is the most frequent neoplasm in Europe. According to the International Agency for Research on Cancer, there were an estimated 429,900 cases diagnosed in Europe in 2006, with an age-standardised incidence rate of 110 cases per 100,000 women.It is also the most frequent cancer in Spanish women, accounting for one forth of female cancer cases, and its incidence is increasing around 2-3% per year. Changes in reproductive behaviour and life style along with the introduction of hormone replacement therapy are partially responsible of this trend. Our country, with an estimated age-standardised incidence rate of 93.6 cases per 100,000 women-year in 2006, occupies an intermediate position between Western and Eastern European countries.This tumour also represents an important cause of female mortality. In 2005, it caused 5,703 deaths in Spanish women, with an age-standardised mortality rate of 18.6 per 100,000 women-year. However, since the 90’s, breast cancer mortality is declining thanks to earlier diagnosis derived from population screening programs and to therapeutical advances. In Spain this downward trend has started in 1993, declining a 2.4% per year.In Europe, 5-year global survival is close to 79%, lower than EEUU survival estimates (90%). Breast cancer survival has risen in recent years. In Spain, 5-year survival is around 83%, significantly higher than European average. Sí

Pleural cancer mortality is an acknowledged indicator of exposure to asbestos and mesothelioma mortality but in 15%-20% of cases no exposure can be recalled. In the past, asbestos was used in many industries and it is still found in many installations. Our objective was to ascertain whether there might be excess pleural cancer mortality among populations residing in the vicinity of Spanish industrial installations that are governed by the Integrated Pollution Prevention and Control (IPPC) Directive and the European Pollutant Release and Transfer Register Regulation and report their emissions to air. An ecological study was designed to examine pleural cancer mortality at a municipal level (8098 Spanish towns) over the period 1997-2006, during which 2146 deaths were registered. We conducted an exploratory "near vs. far" analysis to estimate the relative risks (RRs) of towns situated at a distance of

BACKGROUND: Although breastfeeding is the ideal way of nurturing infants, it can be a source of exposure to toxicants. This study reports the concentration of Hg, Pb and Cd in breast milk from a sample of women drawn from the general population of the Madrid Region, and explores the association between metal levels and socio-demographic factors, lifestyle habits, diet and environmental exposures, including tobacco smoke, exposure at home and occupational exposures. METHODS: Breast milk was obtained from 100 women (20 mL) at around the third week postpartum. Pb, Cd and Hg levels were determined using Atomic Absorption Spectrometry. Metal levels were log-transformed due to non-normal distribution. Their association with the variables collected by questionnaire was assessed using linear regression models. Separate models were fitted for Hg, Pb and Cd, using univariate linear regression in a first step. Secondly, multivariate linear regression models were adjusted introducing potential confounders specific for each metal. Finally, a test for trend was performed in order to evaluate possible dose-response relationships between metal levels and changes in variables categories. RESULTS: Geometric mean Hg, Pb and Cd content in milk were 0.53 μg L(-1), 15.56 μg L(-1), and 1.31 μg L(-1), respectively. Decreases in Hg levels in older women and in those with a previous history of pregnancies and lactations suggested clearance of this metal over lifetime, though differences were not statistically significant, probably due to limited sample size. Lead concentrations increased with greater exposure to motor vehicle traffic and higher potato consumption. Increased Cd levels were associated with type of lactation and tended to increase with tobacco smoking. CONCLUSIONS: Surveillance for the presence of heavy metals in human milk is needed. Smoking and dietary habits are the main factors linked to heavy metal levels in breast milk. Our results reinforce the need to strengthen national food safety programs and to further promote avoidance of unhealthy behaviors such as smoking during pregnancy.

BACKGROUND: Prostate cancer is the second most common type of cancer among men but its aetiology is still largely unknown. Different studies have proposed several risk factors such as ethnic origin, age, genetic factors, hormonal factors, diet and insulin-like growth factor, but the spatial distribution of the disease suggests that other environmental factors are involved. This paper studies the spatial distribution of prostate cancer mortality in an industrialized area using distances from each of a number of industrial facilities as indirect measures of exposure to industrial pollution. MATERIALS AND METHODS: We studied the Gran Bilbao area (Spain) with a population of 791,519 inhabitants distributed in 657 census tracts. There were 20 industrial facilities within the area, 8 of them in the central axis of the region. We analysed prostate cancer mortality during the period 1996-2003. There were 883 deaths giving a crude rate of 14 per 100,000 inhabitants. We extended the standard Poisson regression model by the inclusion of a multiplicative non-linear function to model the effect of distance from an industrial facility. The function's shape combined an elevated risk close to the source with a neutral effect at large distance. We also included socio-demographic covariates in the model to control potential confounding. RESULTS: We aggregated the industrial facilities by sector: metal, mineral, chemical and other activities. Results relating to metal industries showed a significantly elevated risk by a factor of approximately 1.4 in the immediate vicinity, decaying with distance to a value of 1.08 at 12km. The remaining sectors did not show a statistically significant excess of risk at the source. DISCUSSION: Notwithstanding the limitations of this kind of study, we found evidence of association between the spatial distribution of prostate cancer mortality aggregated by census tracts and proximity to metal industrial facilities located within the area, after adjusting for socio-demographic characteristics at municipality level. We thank the Basque Government for providing census tract mortality and geographical data needed to carry out this study. This study was funded by Grant No. FIS: PI040041 from the Carlos III Institute of Health.

BACKGROUND AND OBJECTIVES: To estimate the temporal trend of the cervical cancer mortality rates among Autonomous Communities (AACC) in Spain. MATERIAL AND METHODS: Individual death cases recorded as "cervical cancer', 'corpus uteri cancer' and 'uterus, site unspecified' -codes 180,182 and 179 in ICD8 and 9 and codes C53, C54 and C55 in ICD 10- were obtained, as well as women population estimates broken down by age and AACC from the Spanish National Institute for Statistics (INE). To correct distortions due to increasing improvement in death certification, deaths from 'uterus, site unspecified' were reallocated. Using the European standard population, age-adjusted mortality rates were calculated per year and AACC. Annual percent change (APC) and joinpoints, if existed, were estimated using Joinpoint regression analysis for all women and two broad age-groups: younger and older than 50 years. RESULTS: Cervical cancer mortality rates follow a decreasing trend, with important differences among AACC. Catalonia (PCA -4.55; IC95%: -4.85,-4.23), and Navarra (PCA -4.31; IC95% -5.85,-2.75) decreased more their annually mortality rates than Madrid (PCA -2.32; IC95%: -2.93, -1.70), Canarias (PCA -2,36; IC95% -3.00,-1.72) or Galicia (PCA -2.60; IC95% -3.07,-2.10), which showed the less marked decreased. CONCLUSIONS: Cervical cancer mortality is decreasing in Spain. Trend differences among CCAA could be related to organizational differences and coverages of their screening programs, disparities in exposure to HPV and socioeconomic level as well as to differences in socioeconomic factors.

Tomado de la cubierta : "Manual de Método Epidemiológico" El presente volumen incluye trece temas elaborados por diferentes autores, todos ellos expertos en salud pública y profesores de la Escuela Nacional de Sanidad, con la orientación fundamental de servir de apoyo a la docencia del método epidemiológico. Así, partiendo de la definición de epidemiología y de la descripción de sus usos potenciales, se describen los conceptos básicos de este método científico, sus principales diseños de investigación, los métodos básicos de análisis de datos, las técnicas de control de sesgos y factores de confusión, las bases de la inferencia causal y los aspectos fundamentales de la epidemiología clínica en el escenario actual.

OBJECTIVES: To study the geographical pattern of mortality caused by haematological tumours in Spain at the municipal level using three Bayesian models and to compare their goodness of fit. METHODS: The fitted Bayesian hierarchical models were: (1) the Besag York and Molliè (BYM) model; (2) a model based on zero-inflated Poisson (ZIP) distribution, which allowed a large number of event-free areas; and (3) a mixture of distributions that enabled discontinuities (jumps in the pattern) to be modelled. The three models allow smoothed relative risk maps to be obtained for the all countries. The goodness of fit was evaluated using the deviance information criteria. RESULTS: The three models yielded similar results. The ZIP model plotted a pattern almost identical with the BYM model. The goodness-of-fit criteria indicate that the mixture model is the one that best fits our data. Haematological tumours display a geographical pattern that could be partly explained by environmental determinants, as many of the highest-risk towns are located in heavily industrialised areas. CONCLUSIONS: The choice of one or another model has scant practical consequences. The pattern of distribution supports the hypothesis that differences in lifestyles, air/industrial pollution and migratory phenomena may determine the pattern of urban mortality due to these tumours. Funding: This study was financed by Grant Number EPY‐1176/02 from the Carlos III Institute of Health (ISCIII) and RCESP FIS‐C03/09 (Spanish Network for Cooperative Research in Epidemiologyand Public Health).

STUDY OBJECTIVE: To describe time trends in gastric cancer incidence in Zaragoza and Navarre, and to investigate time period and birth cohort as determinants of such trends. DESIGN: Cases from two registries were grouped into five year intervals and the following were calculated: age specific and sex specific incidence rates, and the male to female ratio. Log linear models including age, period of diagnosis, and birth cohort were fitted. SETTING: The Zaragoza Cancer Registry covers the province of Zaragoza, which has a population of 824,776 (403,755 men and 421,021 women). The Navarre Cancer Registry covers the province of Navarre which has 512,512 inhabitants (254,786 men and 257,726 women). In both cases population figures were based on the late census. PATIENTS: These comprised incident cases of gastric cancer reported to the Zaragoza Cancer Registry in 1963-87 and to the Navarre Cancer Registry in 1973-87. MAIN RESULTS: Navarre registered higher adjusted and cumulative rates than Zaragoza for both sexes. In both provinces, there were relative declines in the rates for men and women of 3% and 4% respectively per year. In Zaragoza, the risk of developing stomach cancer fell in generations born between 1888 and 1933, and rose in subsequent birth cohorts in both sexes, while in Navarre the cohort effect showed an approximately linear risk for both sexes. Both provinces recorded increases in risk associated with cohorts born between 1933 and 1943. CONCLUSION: The incidence rates of gastric cancer fell in both Zaragoza and Navarre. The reason for the greater incidence of gastric cancer in Navarre remains unknown. Trends in rates seem to be mainly linked to birth cohort. Increases in risk in generations born after 1933 may be ascribable to nutritional deficiencies in the early years of life. Funding: this study was supported by the Health Research Fund of the Spanish Ministry of Health (Fondo de Investigacion Sanitaria, grant 94/150). Sí

Fundamentos: El cáncer de próstata (CaP) es el de mayor incidencia entre los varones y sin embargo se conoce muy poco sobre sus factores de riesgo. El presente artículo tiene por objetivo conocer la incidencia hospitalaria, tendencia y distribución municipal del CaP en el área de salud de León (ASL). Métodos: Fueron incluidos los casos nuevos de cáncer de próstata (CIE-9: 185, CIE-10: C61) del registro hospitalario de tumores del Complejo Asistencial Universitario de León, entre 1996 y 2010 en sujetos con residencia en el ASL. Se calcularon las incidencias hospitalarias brutas trienales y ajustadas a población mundial y europea. Como denominador se utilizaron los datos del Instituto Nacional de Estadística de población desagregada por grupos quinquenales de edad de residentes en municipios del ASL. Para el análisis de la distribución espacial se estimaron los riesgos relativos (RR) municipales suavizados mediante el ajuste del modelo de Besag, York y Mollié y sus probabilidades posteriores de que los RR fuesen >1 (PP), utilizando métodos bayesianos. Resultados: Se incluyeron 3.366 casos. Las tasas estandarizadas con población europea ascendieron de 30,3 (1996-98) a 119,0 (2008-2010) casos nuevos por 100.000 hombres. El número de casos órgano-confinados pasó de 281 (1999-2001) a 999 (2008-2010). Las determinaciones de PSA ascendieron de 30.985 (1999-2001) a 117.396 (2008-2010). Conclusiones: Se observó un gran incremento de la frecuencia de CaP a expensas de los casos órgano-confinados, que correlacionan muy bien con las determinaciones de PSA llevadas a cabo en el ASL. No hubo diferencias de interés en la distribución municipal de las incidencias. Background: Prostate cancer (PC) is the most prevalent among men and yet its risk factors are little known. This article aims to determine the hospital incidence, trend and municipal distribution of PC in Health Area of León (HAL). Methods: We included new cases of prostate cancer (ICD-9: 185, ICD-10: C61) enrolled in the Hospital Tumor Registry of the Complejo Asistencial Universitario de León, between 1996 to 2010 with residence in HAL. We calculated crude triennial hospital incidences and adjusted at global and European population. As denominator we used the INE population data disaggregated by five-year age groups of residents in municipalities of the HAL. To analyze the spatial distribution, we estimated municipal relative risks (RR) smoothed by fitting the Besag, York and Mollié model and the posterior probability (PP) of RR >1 using Bayesian methods. Results: 3,366 cases were included. Standardized rates at European population amounted of 30.3 (1996-98) to 119.0 (2008-2010) new cases per 100,000 men. The number of organ-confined cases were increased from 281 (1999-2001) to 999 (2008-2010). PSA determinations amounted from 30,985 (1999-2001) to 117 396 (2008-2010). Conclusions: A great increase was observed in the frequency of PC at the expense of organ-confined cases which correlate very well with PSA determinations performed in HAL. There were no differences of interest in the municipal distribution incidences.

Fundamentos: El cáncer de mama es el más frecuente en las mujeres. El objetivo del presente estudio fue analizar la incidencia y distribución geográfica del cáncer de mama invasivo en el área de salud de León (ASL). Métodos: Estudio observacional descriptivo en el que se incluyeron mujeres con diagnóstico de neoplasia maligna de mama (CIE-9:174, CIE-10: C50) del Registro Hospitalario de Tumores del Centro Asistencial Universitario de León, entre 1/1/1996 y 31/12/2010 y con residencia en el ASL. Para el análisis de la distribución espacial se estimaron los riesgos relativos (RR) municipales suavizados mediante el ajuste del modelo de Besag, York y Mollié y sus probabilidades posteriores de que los RR fuesen > 1 (PP), utilizando métodos bayesianos. Resultados: Se incluyó un total de 2.379 casos. El número de casos nuevos y las tasas de incidencia brutas en cada trienio fueron de 72,7 (1996-1998) a 101,5 (2008-2010) por 100.000 mujeres. Las tasas a población europea por 100.000 mujeres ascendieron de 58,0 en el primer trienio y a 69,4 en el último. Se observó un incremento anual promedio del 1,3%. Varios municipios del ASL presentaron riesgos superiores al 10 %. Las PP solo fueron superiores a 0,9 en el municipio de León. Conclusiones: Las tasas observadas son de las más bajas de España. Sin embargo, el número de casos y las tasas de incidencia se incrementaron de manera mantenida en el periodo estudiado. Background: Breast cancer is the most common amongst women. The aim of this study was to analyze the incidence and geographical distribution of breast cancer in the health area of León. Methods: We designed an observational descriptive study that included women enrolled in the Hospital Tumor Registry of the Centro Asistencial Universitario in León with a diagnosis of breast malignant neoplasm (ICD-9: 174, ICD-10: 50) between 01/01/1996 and 31/12/2010 and resident in the health area of León. To study the spatial distribution, we estimated municipal relative risks (RR) smoothed by fitting the Besag, York and Mollié model and the posterior probability (PP) of RR > 1 using Bayesian methods. Results: A total of 2379 cases were included. The number of new cases and the crude incidence rate have both increased in every triennium, from 72,7 (1996-1998) to 101,5 (2008-2010) per 100,000 women. The age adjusted rates per 100,000 women (European standard population) increased from 58,0 during the first triennium to 69,4 during the last one. An average annual increase of 1,3% was observed. Several municipalities from the health area of León showed risks higher than a 10%. The PP were higher than 0.9 only in the municipality of León. Conclusions: The observed rates are among the lowest in our country. Nevertheless, the number of cases and the incidence rates have increased progressively.

Aunque la experiencia en el estudio de las desigualdades en la mortalidad en las ciudades españolas es amplia, quedan grandes núcleos urbanos que no han sido investigados utilizando la sección censal como unidad de análisis territorial. En este contexto se sitúa el proyecto coordinado «Desigualdades socioeconómicas y medioambientales en la mortalidad en ciudades de España. Proyecto MEDEA», en el cual participan 10 grupos de investigadores de Andalucía, Aragón, Cataluña, Galicia, Madrid, Comunitat Valenciana y País Vasco. Cabe señalar cuatro particularidades: a) se utiliza como área geográfica básica la sección censal; b) se emplean métodos estadísticos que tienen en cuenta la estructura geográfica de la región de estudio para la estimación de riesgos; c) se aprovechan las oportunidades que ofrecen 3 fuentes de datos complementarias (información sobre contaminación atmosférica, información sobre contaminación industrial y registros de mortalidad), y d) se emprende un análisis coordinado de gran alcance, favorecido por la implantación de la redes temáticas de investigación. El objetivo de este trabajo es explicar los métodos para la suavización de indicadores de mortalidad en el proyecto MEDEA. El artículo se centra en la metodología y los resultados del modelo de mapa de enfermedades de Besag, York y Mollié (BYM). Aunque en el proyecto se han suavizado, mediante el modelo BYM, las razones de mortalidad estandarizadas (RME) correspondientes a 17 grandes grupos de causas de defunción y 28 causas específicas, aquí se aplica esta metodología a la mortalidad por cáncer de tráquea, de bronquios y de pulmón en ambos sexos en la ciudad de Barcelona durante el período 1996-2003. Como resultado se aprecia un diferente patrón geográfico en las RME suavizadas en ambos sexos. En los hombres se observan unas RME mayores que la unidad en los barrios con mayor privación socioeconómica. En las mujeres este patrón se observa en las zonas con un mayor nivel socioeconómico. Although there is some experience in the study of mortality inequalities in Spanish cities, there are large urban centers that have not yet been investigated using the census tract as the unit of territorial analysis. The coordinated project «Socioeconomic and environmental inequalities in mortality in Spanish cities. The MEDEA project» was designed to fill this gap, with the participation of 10 groups of researchers in Andalusia, Aragon, Catalonia, Galicia, Madrid, Valencia, and the Basque Country. The MEDEA project has four distinguishing features: a) the census tract is used as the basic geographical area; b) statistical methods that include the geographical structure of the region under study are employed for risk estimation; c) data are drawn from three complementary data sources (information on air pollution, information on industrial pollution, and the records of mortality registrars), and d) a coordinated, large-scale analysis, favored by the implantation of coordinated research networks, is carried out. The main objective of the present study was to explain the methods for smoothing mortality indicators in the context of the MEDEA project. This study focusses on the methodology and the results of the Besag, York and Mollié model (BYM) in disease mapping. In the MEDEA project, standardized mortality ratios (SMR), corresponding to 17 large groups of causes of death and 28 specific causes, were smoothed by means of the BYM model; however, in the present study this methodology was applied to mortality due to cancer of the trachea, bronchi and lung in men and women in the city of Barcelona from 1996 to 2003. As a result of smoothing, a different geographical pattern for SMR in both genders was observed. In men, a SMR higher than unity was found in highly deprived areas. In contrast, in women, this pattern was observed in more affluent areas.