A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (P-replication=0.042; P-pooled=5.523x10(-03); OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (P-replication=0.039; P-pooled=6.985x10(-5); OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction.

Neuroprotective Effect of Melatonin: A Novel Therapy against Perinatal Hypoxia-Ischemia

17 p.

First occurrence of Mosasauridae (Squamata) in the Maastrichtian (latest Cretaceous) of Alicante (Valencia Community, Eastern Spain)

8 p.

Judíos, conversos, marranos: la historia de una verdad a medias

Antonio Duplá Ansuátegui, Piedad Frías Nogales e Iban Zaldúa (editores)

Evidence for classification of c.1852_1853AA > GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

Downscaling of surface moisture flux and precipitation in the Ebro Valley (Spain) using analogues and analogues followed by random forests and multiple linear regression

In this paper, reanalysis fields from the ECMWF have been statistically downscaled to predict from large-scale atmospheric fields, surface moisture flux and daily precipitation at two observatories (Zaragoza and Tortosa, Ebro Valley, Spain) during the 1961-2001 period. Three types of downscaling models have been built: (i) analogues, (ii) analogues followed by random forests and (iii) analogues followed by multiple linear regression. The inputs consist of data (predictor fields) taken from the ERA-40 reanalysis. The predicted fields are precipitation and surface moisture flux as measured at the two observatories. With the aim to reduce the dimensionality of the problem, the ERA-40 fields have been decomposed using empirical orthogonal functions. Available daily data has been divided into two parts: a training period used to find a group of about 300 analogues to build the downscaling model (1961-1996) and a test period (19972001), where models' performance has been assessed using independent data. In the case of surface moisture flux, the models based on analogues followed by random forests do not clearly outperform those built on analogues plus multiple linear regression, while simple averages calculated from the nearest analogues found in the training period, yielded only slightly worse results. In the case of precipitation, the three types of model performed equally. These results suggest that most of the models' downscaling capabilities can be attributed to the analogues-calculation stage.

A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer

12 p.

El valor de la información : cantidad óptima de información

El documento es de utilidad para los estudiantes de la asignatura de Economía de la Información y para cualquier estudiante o persona interesada en problemas de decisión bajo incertidumbre. El documento está estructurado en siete secciones. Entre los temas analizados se incluyen: cálculo del valor de un servicio de información completa y del valor de un servicio de información incompleta en varios contextos y problemas distintos, presentación y discusión del proceso de revisión de creencias por parte del decisor cuando recibe información, consideración de situaciones en las que la incertidumbre tiene varios componentes o en las que el decisor recibe varias informaciones simultáneamente y determinación del nivel de información que es óptimo para el decisor. Se incluyen también once ejercicios que aplican los análisis desarrollados. Cada ejercicio se presenta con solución, a veces de forma abreviada. La presentación se completa con unas lecturas recomendadas

Choice under Risk : Theory and Applications

Es útil para estudiantes de postgrado (Master y Doctorado) en cursos de Economía o de Microeconomía en los que se analicen problemas de Decisión en condiciones de Riesgo o Incertidumbre. El documento comienza explicando la Teoría de la Utilidad Esperada. A continuación se estudian la aversión al riesgo, los coeficientes de aversión absoluta y relativa al riesgo, la relación “más averso que” entre agentes económicos y los efectos riqueza sobre las decisiones en algunas relaciones de preferencia utilizadas frecuentemente en el análisis económico. La sección 4 se centra en la comparación entre alternativas arriesgadas en términos de rendimiento y riesgo, considerando la dominancia estocástica de primer y segundo orden y algunas extensiones posteriores de esas relaciones de orden. El documento concluye con doce ejercicios resueltos en los que se aplican los conceptos y resultados expuestos en las secciones anteriores a problemas de decisión en varios contextos

Valor de la Información. Cantidad óptima de información. Valor de la flexibilidad

El documento es de utilidad para los estudiantes de la asignatura de Economía de la Información y para cualquier estudiante o persona interesada en problemas de decisión bajo incertidumbre estáticos o dinámicos. El documento está estructurado en ocho secciones. Entre los temas analizados se incluyen: cálculo del valor de servicios de información, completa o incompleta, en varios contextos y problemas distintos, análisis del proceso de revisión de creencias cuando se recibe información, consideración de situaciones en las que la incertidumbre tiene varios componentes o en las que el decisor recibe varias informaciones simultáneamente, determinación del nivel de información que es óptimo para el decisor y cálculo del valor de la flexibilidad cuando la información llega con el paso del tiempo. Se incluyen también catorce Ejercicios que aplican los análisis desarrollados. Cada Ejercicio se presenta con su solución, a veces en forma abreviada. El documento se completa con unas Lecturas recomendadas.

La legitimidad social de las Organizaciones Internacionales Intergubernamentales

519 p.

Las estrategias competitivas de los operadores de transporte marítimo de contenedores en línea regular

459 p.

Regulación empresarial voluntaria y medio ambiente : análisis de la adopción de ISO 14001 en las organizaciones de la CAPV

578 p.

La música en la educación primaria y en las escuelas de música : la necesario coordinación. Análisis para futuros planes de intervención educactiva en la Comunidad Autónoma Vasca

V.I: 491 p. y V.II: 335 p.

Efecto de la resección hepática sobre el comportamiento de las células tumorales residuales y utilidad del ATRA para controlar dicho efecto en un modelo experimenta

240 p. : il., graf.