The PANcreatic Disease ReseArch (PANDoRA) consortium: Ten years’ experience of association studies to understand the genetic architecture of pancreatic cancer

Pancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groupsAssociazione Italiana per la Ricerca sul Cancro (AIRC) under IG 2019—ID. 23672 project—P.I. Campa Daniele and IG 2021 ID – 26201 project P.IThe Czech Ministry of Health, NU21–07–00247 and from Programme EXCELESID Project No. LX22NPO5102. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo (FG)Italian Minister of Health, Ricerca Corrente program 2022–2024Cancer Research UK (C7690/A26881, C18616/A25153) and Pancreatic Cancer UK. Sample accrual at the Amsterdam UMC was supported by the AMC FoundationCOST Action TRANSPANCA21116COST (European Cooperation in Science and Technology

Evaluation of 4 prognostic indices in follicular lymphoma treated in first line with immunochemotherapy

Several clinical risk models have been proposed to predict the outcome of follicular lymphoma (FL). The development of next-generation sequencing technologies has allowed the integration of somatic gene mutations into clinical scores to build genotyped-based risk models, such as the m7–Follicular Lymphoma International Prognostic Index (FLIPI). We explored 4 clinical or clinicogenetic-risk models in patients with symptomatic FL who received frontline immunochemotherapy. Of 191 patients with FL grades 1 to 3a, 109 were successfully genotyped. The treatment consisted of rituximab (R) plus cyclophosphamide, vincristine, and prednisone (R-CVP)/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (72.5%) or R-bendamustine (R-B) (27.5%). The proportion of cases classified as high risk for FLIPI, FLIPI-2, PRIMA–prognostic index, or m7-FLIPI were 39.3%, 14%, 30.3%, and 22%, respectively. No case with low-intermediate FLIPI was upgraded in the m7-FLIPI, but 18 of the 42 high-risk patients with FLIPI were downgraded to low-risk m7-FLIPI. The sensitivity and specificity for the prediction of POD24 were highest for FLIPI. The discrimination between progression-free survival (PFS) and overall survival (OS) was the best for FLIPI (c-index: 0.644 and 0.727, respectively). When analyzed only in patients treated with R-B, m7-FLIPI showed a higher discrimination between PFS and OS. Thus, the FLIPI remains the clinical risk score with higher discrimination in patients with advanced FL treated with immunochemotherapy; however, the performance of the m7-FLIPI should be further investigated in patients treated with R-B.Instituto de Salud Carlos III (ISCIIIEuropean Union (FIS-FEDER PI15/0459, FIS-FEDER PI19/00034GILEAD GLD18/00117, 2017SGR205, and PT20/00023)Xarxa de Banc de Tumors de CatalunyaPla Director d’Oncologia de CatalunyaThe biobank of the Fundació

Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, we evaluated whether 41 GWAS-identified risk variants for CLL could influence overall survival (OS) and disease progression, defined as time to first treatment (TTFT) in a cohort of 1039 CLL cases ascertained through the CRuCIAL consortium. Although this is the largest study assessing the effect of GWAS-identified susceptibility variants for CLL on OS, we only found a weak association of ten single nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did not remain significant after correction for multiple testing. In line with these results, polygenic risk scores (PRSs) built with these SNPs in the CRuCIAL cohort showed a modest association with OS and a low capacity to predict patient survival, with an area under the receiver operating characteristic curve (AUROC) of 0.57. Similarly, seven SNPs were associated with TTFT (p < 0.05); however, these did not reach the multiple testing significance threshold, and the meta-analysis with previous published data did not confirm any of the associations. As expected, PRSs built with these SNPs showed reduced accuracy in prediction of disease progression (AUROC = 0.62). These results suggest that susceptibility variants for CLL do not impact overall survival and disease progression in CLL patientsHorizon 2020 856620Instituto de Salud Carlos III Spanish GovernmentMarie Curie Actions PI17/02256 PI20/01845Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades y FEDER PY20/01282United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) P50 CA97274 R01 CA9215

GWAS-Identified Variants for Obesity Do Not Influence the Risk of Developing Multiple Myeloma: A Population-Based Study and Meta-Analysis

Multiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells in the bone marrow that secrete specific monoclonal immunoglobulins into the blood. Obesity has been associated with the risk of developing solid and hematological cancers, but its role as a risk factor for MM needs to be further explored. Here, we evaluated whether 32 genome-wide association study (GWAS)-identified variants for obesity were associated with the risk of MM in 4189 German subjects from the German Multiple Myeloma Group (GMMG) cohort (2121 MM cases and 2068 controls) and 1293 Spanish subjects (206 MM cases and 1087 controls). Results were then validated through meta-analysis with data from the UKBiobank (554 MM cases and 402,714 controls) and FinnGen cohorts (914 MM cases and 248,695 controls). Finally, we evaluated the correlation of these single nucleotide polymorphisms (SNPs) with cQTL data, serum inflammatory proteins, steroid hormones, and absolute numbers of blood-derived cell populations (n = 520). The meta-analysis of the four European cohorts showed no effect of obesity-related variants on the risk of developing MM. We only found a very modest association of the POC5rs2112347G and ADCY3rs11676272G alleles with MM risk that did not remain significant after correction for multiple testing (per-allele OR = 1.08, p = 0.0083 and per-allele OR = 1.06, p = 0.046). No correlation between these SNPs and functional data was found, which confirms that obesity-related variants do not influence MM risk.Instituto de Salud Carlos III (Madrid, Spain; PI17/02256 and PI20/01845)Consejería de Salud y Familia de la Junta de Andalucía (PY20/01282)Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS (01ZX1309

Posneoliberalismo y desigualdades sociales

El “giro a la izquierda” ha sido el fenómeno más importante que ha acaecido en América Latina en lo que va del presente siglo. Dada su intencionalidad posneoliberal puede ser interpretada como el tercer momento rousseauniano en la historia de la región ya que intenta revertir las desigualdades sociales generadas por el (neo)liberalismo precedente. Tomando como referencia los tres casos más “radicales” (Venezuela con el chavismo; Bolivia con el Movimiento al Socialismo, MAS, y Ecuador con la Revolución Ciudadana) se analizan tanto los cambios operados en la esfera de la distribución, compuesta por los mercados básicos, así como las transformaciones acaecidas en la esfera de la redistribución. Se plantea como hipótesis que no habido cambios distributivos sustantivos pero sí transformaciones redistributivas importantes. Estas han consistido en la ampliación de la ciudadanía social básica a la cual ha sido incorporada sectores subalternos históricamente excluidos. Esto no ha supuesto una mera continuidad y profundización de la políticas (neo)liberales basadas en la invención de la “pobreza”. Esta interpretación se enmarca en el contexto de rentismo que caracteriza el desarrollo capitalista de estas tres sociedades. Se concluye comparando este tercer momento rousseauniano con su precedente para entender su naturaleza y alcance

Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers forMultipleMyeloma: AMeta-Analysis of Three Large Cohorts and Functional Characterization

European Union’s Horizon 2020 research and innovation program, N 856620Instituto de Salud Carlos III and FEDER (Madrid, SpainPI17/02256 and PI20/01845), Consejería de Transformación Económica, Industria, Conocimiento y UniversidadesDietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS [01ZX1309]National Cancer Institute of the National Institutes of Health under award numbers: R01CA186646, U01CA249955 (EEB)Science and Technology (FCT)—project UIDB/50026/2020UIDP/50026/2020 and by the project NORTE-01-0145-FEDER-000055PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF

Huellas terópodas gigantes en el Jurásico Superior de Marruecos. Yacimiento de Aït Mazight (Atlas Central)

A new small site, not always outcropping, with large and giant theropod tracks in the Upper Jurassic of the Central High Atlas of Morocco is described. The ichnites and the typology of the rocks of the site are similar to those of the Iouaridène sites with which there is no cartographic continuity. The particular characters of the tracks and trackways are analyzed and highlighted and a hypothesis of distribution of this type of dinosaurs is pointed outSe describe un nuevo yacimiento pequeño, no siempre aflorante, con huellas terópodas grandes y gigantes en el Jurásico Superior del Alto Atlas Central de Marruecos. Las icnitas y la tipología de las rocas en las que yacen son similares a las de los yacimientos de Iouaridène con los que no hay continuidad cartográfica. Se analizan y destacan los caracteres particularesde las huellas y rastrilladas y se apunta una hipótesis de distribución de este tipo de dinosaurio

Social exclusion, violence and household. Evidence and analysis from Central America

Exclusión social y violencia son fenómenos articulados de diversas formas. El presente artículo busca indagar una de estas articulaciones que tiene lugar en la esfera de lo doméstico. Las reflexiones provienen de una investigación en curso que compara comunidades urbanas en Costa Rica y en El Salvador. A partir de los datos provenientes de una encuesta de hogares aplicada en las comunidades investigadas; se quiere mostrar cómo la exclusión social tiene una proyección en el ámbito de lo doméstico que encuentra su traducción en términos de violencia, no sólo entre los miembros del hogar sino que también se externa hacia la comunidad.Social exclusion and violence are phenomena intertwined in different ways. The current article seeks to explore one of this articulations happening at the household. Reflections are based on the data provided by a household survey applied in several urban communities in Costa Rica and El Salvador. The analysis shows how social exclusion is projected within the household generating violence which affects not only family members but also other members of the community.UCR::Vicerrectoría de Docencia::Ciencias Sociales::Facultad de Ciencias Sociales::Escuela de SociologíaUCR::Vicerrectoría de Docencia::Ciencias Sociales::Facultad de Ciencias Económicas::Escuela de EstadísticaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Centro Centroamericano de Población (CCP