Ramon Clèries

The influence of alcohol consumption and hepatitis B and C infections on the risk of liver cancer in Europe

BACKGROUND/AIMS To assess the variability of liver cancer (LC) risk associated with hepatitis B (HBV) and hepatitis C (HCV) viruses and alcohol intake in 2002 throughout Europe. METHODS Incidence data were obtained from population-based cancer registries whereas mortality, HBV, HCV and alcohol exposures were obtained from the WHO databases. Relative risk of LC and their posterior probabilities to be >1 were obtained and plotted in maps through a Bayesian random effects model. RESULTS HBV prevalence >2% increased the risk of developing LC a 15% in men and 21% in women; HCV prevalence >2%, 54% in men and 33% in women and, pure alcohol intake >11l, 26% and 14%, respectively (all of them statistically significant). These risk factors played a similar role in the risk of dying from LC among men, whereas HBV and alcohol were not statistically significant among women. Significant high LC risk, after HBV/HCV and alcohol adjustment were observed for both sexes in: Hungary, Moldova, Romania, Croatia, Greece, Italy, Spain, France and Austria. CONCLUSIONS South-North and East-West decreasing gradients for LC risk were observed in Europe. HBV, alcohol and, mainly, HCV are independent risk factors that could explain this geographical pattern.

Cofactors associated with liver disease mortality in an HBsAg-positive Mediterranean cohort: 20 years of follow-up

The risk of developing liver cancer in hepatitis B virus (HBV) carriers differs across geographical areas, suggesting that exposure to other risk factors may contribute to HBV‐linked cancer risk. Our study estimates the mortality due to liver disease and the role of other risk factors in a Spanish HBV cohort. 2,352 hepatitis B surface antigen (HBsAg)‐positive and 15,504 HBsAg‐negative subjects were identified among blood donors during 1972–1985 and were followed until December 2000 through the Mortality Registry. Clinical examination and an epidemiological questionnaire were performed on 1,000 HBsAg‐positive survivors during 1994–1996. In subjects deceased from liver disease, medical records were revised and relatives were interviewed. A nested case‐control analysis was conducted comparing both groups. In HBsAg‐positive men, an excess mortality from liver cancer [standardized mortality ratio (SMR): 14.1; 7.7–23.6], cirrhosis (SMR: 10.5; 7.0–15.1), haematological neoplasms (SMR: 3.2; 1.2–6.9) and AIDS was detected (SMR: 5.5; 2.2–11.4). In women, an excess was found for cirrhosis (SMR: 7.2; 1.4–21.1). Progression factors to liver disease were alcohol intake [odds ratio (OR): 6.3; 3.1–12.8], diabetes (OR: 3.6; 1.3–9.6), HBV replication (OR: 50.0; 14.9–167.3) and hepatitis C virus (HCV) infection (OR: 27.4; 7.1–107.7). In conclusion, in Spain after 20 years of follow‐up, chronic HBV exposure appears as a major risk factor for liver cancer among men and for cirrhosis in both sexes. The risk of death from liver disease among HBV carriers with the presence of HBV replication, HCV, alcohol consumption and diabetes was significantly increased and suggests synergism among these exposures and HBV. Mortality from haematological neoplasms was detected and could be associated to HIV coinfection. These results support screening and adequate follow‐up among HBsAg‐positive subjects at high risk to develop liver disease, particularly when these risk cofactors are present.

Rising trends in incidence of cutaneous malignant melanoma and their future projections in Catalonia, Spain: increasing impact or future epidemic?

Background  During the past decades, there has been a substantial increase in the incidence of cutaneous malignant melanoma (CMM) among all Caucasian populations. Spain presents one of Europe’s lowest incidence and mortality rates.

BootstRatio: A web-based statistical analysis of fold-change in qPCR and RT-qPCR data using resampling methods

Real-time quantitative polymerase chain reaction (qPCR) is widely used in biomedical sciences quantifying its results through the relative expression (RE) of a target gene versus a reference one. Obtaining significance levels for RE assuming an underlying probability distribution of the data may be difficult to assess. We have developed the web-based application BootstRatio, which tackles the statistical significance of the RE and the probability that RE>1 through resampling methods without any assumption on the underlying probability distribution for the data analyzed. BootstRatio perform these statistical analyses of gene expression ratios in two settings: (1) when data have been already normalized against a control sample and (2) when the data control samples are provided. Since the estimation of the probability that RE>1 is an important feature for this type of analysis, as it is used to assign statistical significance and it can be also computed under the Bayesian framework, a simulation study has been carried out comparing the performance of BootstRatio versus a Bayesian approach in the estimation of that probability. In addition, two analyses, one for each setting, carried out with data from real experiments are presented showing the performance of BootstRatio. Our simulation study suggests that Bootstratio approach performs better than the Bayesian one excepting in certain situations of very small sample size (N≤12). The web application BootstRatio is accessible through http://regstattools.net/br and developed for the purpose of these intensive computation statistical analyses.

Colorectal cancer mortality in Spain: trends and projections for 1985-2019.

Background and aim To describe colorectal cancer (CRC) mortality trends during 1985–2004 and to estimate CRC mortality projections for the period 2005–2019 in Spain. Material and methods A Bayesian age-period-cohort analysis has been carried out to investigate the effect of the age, period, and birth cohort on CRC mortality in Spain. Mortality projections until 2019 were based on the age-period-cohort model. Results During 1985–1994, CRC mortality increased in both sexes (3.9% yearly in men and 1.5% in women). After 1995, CRC mortality increased in men (1.6%) and leveled off in women (−0.6%). Colon cancer mortality increased for the whole period in men, this increase being lower in the second decade (1985–1994: 5.0%; 1995–2004: 1.8%). In women, colon cancer mortality increased in the first decade (2.8%) and leveled off during the second decade (−0.1%). Rectal cancer mortality increased in men (1.2%) and decreased in women (−1.1%) during the whole study period. Projections showed an increase in the number of CRC deaths in men older than 60 years and a level off in women. Conclusion Although mass screening for CRC in Spain has not been available, the favorable recent changes in CRC mortality trends observed after 1995 could be related to progress in diagnosis and treatment. The projected number of deaths could be used as reference scenario for assessing future impact of new treatments as well as the potential impact of future population-based screening when introduced.

Time trends in incidence and mortality for chronic liver disease and liver cancer in the interval 1980-1997 in Catalonia, Spain.

Background and aims It has been reported that the incidence of liver cancer and intrahepatic bile duct tumours might be increasing in some developed countries. The purpose of this study was to examine time trends of incidence and mortality rates of liver cirrhosis and liver cancer for the period 1980–1997 in Catalonia, Spain. Methods Data were obtained from the Catalan Mortality Registry and the Tarragona Cancer Registry. Joinpoint analysis was used to detect time-related changes in incidence and mortality of liver diseases. The cohort effect on mortality and incidence rates was explored by an age–period–cohort model. Results Mortality from liver cirrhosis decreased during the study period for both sexes and all age groups, with the exception of men aged between 25 and 35 years. No changes in incidence or mortality rates were observed for liver cancer. Mortality rates for intrahepatic bile duct tumours increased in men and women, while incidence rates remained stable. Conclusions This study identified in Catalonia an increase in mortality due to liver cirrhosis among 25–35-year-old men. Mortality rates for intrahepatic bile duct tumours increased for all age groups and both sexes. The former could be related to hepatitis C or B viruses and human immunodeficiency virus co-infection, while the latter remains unexplained.

Tendencias de la mortalidad por cáncer en Cataluña, 1985-2004

Fundamento y objetivo Tanto la situacion epidemiologica como asistencial del cancer en las ultimas 2 decadas ha experimentado grandes cambios y esto ha influido en la mortalidad por esta enfermedad. El objetivo es analizar las tendencias de la mortalidad por cancer en Cataluna, durante los ultimos 20 anos y compararlas con Europa. Sujetos y metodo Los datos de las defunciones ocurridas en Cataluna proceden del registro de mortalidad del Departamento de Salud y estan codificados segun la Clasificacion Internacional de Enfermedades (CIE) (novena revision de 1985-1998 y decima de 1999 a 2004). La poblacion corresponde a la intercensal (1985-2000), censal (2001) y poscensal (2002-2004) del Instituto de Estadistica de Cataluna. Se han calculado las tasas ajustadas por edad (TA) mediante el metodo directo (poblacion estandar mundial de 1960) y las tasas acumuladas (Tac) de 0 a 74 anos. Para evaluar la tendencia se ha ajustado un modelo de Poisson a las TA y se ha estimado el porcentaje de cambio anual (PCA) para los decenios 1985-1994 y 1995-2004 y el global para 1985-2004. Resultados El riesgo de morir por cancer (Tac) ha pasado en los varones del 18,54 al 17,49% y en las mujeres, del 9,24 al 7,69% de 1985 a 2002. En estos anos ha disminuido la mortalidad (PCA) por los canceres de laringe (−2,52%), prostata (−1,11%) y estomago (−2,89%) en varones y estomago (−3,64%) en mujeres. Mostraron cambios de tendencia en los varones el cancer colorrectal (aumento del 2,8% hasta 1994 y estabilizacion posterior), pulmon (crecio el 1,36% hasta 1994 y despues descendio) e higado (aumento no significativo hasta 1994 y luego descenso de -3,13%). En las mujeres la mortalidad por cancer de mama primero aumento (1,48%) y despues disminuyo (−2,72%) significativamente y el de pulmon aumento en todo el periodo, aunque solo en la ultima decada (4,81%) fue estadisticamente significativo. Conclusiones La mortalidad por cancer en las ultimas 2 decadas ha mostrado una tendencia general decreciente, aunque algunas localizaciones aumentan. Comparada con otros paises, Cataluna se encuentra en una situacion mas favorable en el caso de las mujeres que en el de los varones, aunque la evolucion de los ultimos anos ha sido parecida a la de los paises que se encuentran en situacion mas ventajosa.

Incidencia del cáncer de mama en Cataluña: análisis de la tendencia

Fundamento y objetivo: Se analiza la incidencia del cancer de mama en Cataluna en estos ultimos 20 anos llevando a cabo un analisis de edad, periodo y cohorte. Poblacion y metodo: Casos de cancer de mama diagnosticados en mujeres de mas de 25 anos de edad entre 1980 y 1999 en la poblacion cubierta por los registros de cancer de Tarragona y Girona. Para investigar el efecto de la edad, el periodo y la cohorte de nacimiento en la incidencia se utilizaron los modelos de edad, periodo y cohorte propuestos por Decarli y La Vechia y el metodo de Holdford. Resultados: La tasa de incidencia (en mujeres de entre 25 y >= 85 anos), ajustada por edad a la poblacion estandar mundial, ha pasado de 53,9 nuevos casos por 105 en el periodo 1980-1984 a 83,9 por 105 en el periodo 1995-1999. El porcentaje de incremento anual fue del 2,2% (intervalo de confianza del 95%, 1,8-2,6). Segun el modelo de edad, periodo y cohorte, existe un incremento de la incidencia en funcion de la edad y la cohorte de nacimiento, siendo menos importante el efecto del periodo. Conclusiones: La incidencia del cancer de mama ha aumentado significativamente en Cataluna. En este aumento, el efecto cohorte es mas importante que el efecto periodo, lo que indica un cambio en la prevalencia de los factores de riesgo, aunque el mayor empleo de las tecnicas de diagnostico precoz, como la mamografia, explicaria en parte el efecto periodo encontrado.

Cálculo automatizado de la supervivencia relativa vía web: El proyecto WAERS del Instituto Catalán de Oncología

La medida utilizada habitualmente para estimar la supervivencia del cancer es la supervivencia relativa, definida como el cociente entre la supervivencia observada y la esperada. La supervivencia esperada se calcula a partir de la mortalidad de una poblacion de referencia. La disponibilidad y la preparacion de tablas de mortalidad de la poblacion general no es siempre posible y requiere software especifico para su calculo. A tal efecto, el Instituto Catalan de Oncologia (ICO) ha desarrollado la aplicacion WAERS, una aplicacion web que proporciona la estimacion de la supervivencia relativa para una cohorte de pacientes. El usuario debe preparar los datos en un formato especifico y enviarlos a un servidor remoto que se encuentra en el ICO. Este servidor calcula la supervivencia relativa y devuelve los resultados en un fichero a una direccion que ha indicado el usuario. Mediante esta aplicacion, los registros de cancer de base hospitalaria y poblacional y los registros de otras enfermedades pueden estimar la supervivencia relativa de sus cohortes seleccionando a la poblacion de referencia que consideren (provincia o comunidad autonoma). Tambien puede ser util para estudios de mortalidad en cohortes.

Predicting the change in breast cancer deaths in Spain by 2019: a Bayesian approach.

Background: Breast cancer mortality rates have been decreasing in Spain since 1992. Recent changes in demography, breast cancer therapy, and early detection of breast cancer may change this trend. Methods: Using breast cancer mortality data from years 1990 to 2009, we sought to predict the changes in the burden of breast cancer mortality during the years 2005–2019 through a Bayesian age-period-cohort model. The net change in the number of breast cancer deaths between the periods of 2015–2019 and 2005–2009 was separated into changes in population demographics and changes in the risk of death from breast cancer. Results: During the period 1990–2009, breast cancer mortality rates decreased (age-standardized rates per 100,000 women-years 50.6 in 1990–1994 vs. 41.1 in 2005–2009), whereas the number of breast cancer deaths increased (28,149 in 1990–1994; 29,926 in 2005–2009). There was a decrease in the number of cases among women 45–64 years of age (10,942 in 1990–1994; 8,647 in 2005–2009). Changes in population demographics contribute to a total increase of 12.5–12.8% comparing periods 2005–2009 versus 2015–2019, whereas changes in the risk of death from breast cancer contribute to a reduction of 12.9–13.7%. We predict a net decline of 0.1–1.2% in the absolute number of breast cancer deaths comparing these time periods. Conclusions: The decrease in the risk of death from breast cancer may exceed the projected increase in deaths from growing population size and aging in Spain. These changes may also explain the decrease in the absolute number of breast cancer deaths in Spain since 2005.