A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas

GATA4 loss as a result of promoter hypermethylation or somatic mutation promotes growth and chemotherapy resistance of human astrocytomas

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

COMPARACIÓN DE DOS MÉTODOS PARA EVALUAR LA TRANSPORTACIÓN APICAL

The purpose of the present study was to compare a radiographic versus anatomic method for apical transportation measurement in curved root canal. Sixty recently removed human mandibular molars with buccolingual curved root canals ranging from 15º to 45º, were selected. The distal roots were removed to avoid radiographs interferences with mesiodistal incidence. Before been sectioned mesial roots were inclosed in transparent resin using a grilon key-like muffle with modificated Bramante´s procedure. The inclosed teeth were radiographed buccolingually and mesiodistally using a plastic dispositive to allow for standart pre and postinstrumentation radiographs. The roots canals were horizontally sectioned. Cuts made at 3 mm from the apex and photographed. The sections were reassembled in the muffle and the canals were instrumented with manual and mechanized techniques. After instrumentation was finished, radiographs of the teeth and photographs of the segment were taken. Transportation radiographic measurement was made with a micrometer on radiographic projection tracing magnified 8 times, in two planes. Transportation anatomic measurement was made analyzing photographs pre and posinstrumentation using and Image 1.45 Sofware Macintosh computer. Radiographic and anatomic methods showed different data due to the different levels and criteria of measurement. Statistical analysis (ANOVA) showed significant difference (p<0.0001) between radiographic and anatomic methods. Media comparison between radiographic and anatomic transportation, in each group, showed no significant difference (p=0.21).ResumenEl objetivo del presente trabajo fue comparar un método radiográfico con un método anatómico para medir la transportación apical en conductos curvos. Se seleccionaron 60 molares inferiores humanos, con angulaciones en sus conductos mesio-vestibularees de 15º a 45º. La raíz distal de cada pieza fue eliminada, para evitar la interferencia en las radiografías con incidencia mesio-distal. Aplicando el procedimiento propuesto por Bramante modificado, la raíz mesial antes de ser seccionada fue incluida en resina transparente usando una mufla de grilon como llave para la reposición de los fragmentos. Las piezas incluidas fueron radiografiadas con incidencia vestíbulo-lingual y mesio-distal utilizando un dispositivo plástico para sistematizar las tomas radiográficas pre y pos operatorias. Luego, las raíces fueron seccionadas horizontalmente a 3 mm del ápice y fotografiadas. Los segmentos fueron reposicionados en la mufla y los conductos instrumentados con técnicas manual y mecanizada. Completada la instrumentación se tomaron radiografías de las raíces y fotografías de los segmentos. La medición radiográfica de la transportación apical se realizó con calibre micrométrico sobre trazados de las proyecciones ampliadas 8 veces de ambas tomas radiográficas. La medición anatómica se realizó analizando las fotografías pre y pos instrumentación con un equipo de digitalización de imágenes Macintosh (Image 1.45). Los métodos radiográfico y anatómico presentan datos diferentes debido a los distintos niveles y criterios de medición. El análisis estadístico (ANOVA) mostró diferencias significativas entre el método radiográfico y el método anatómico (p<0.0001). La comparación entre las medidas de transportación obtenidas radiográficamente y anatómicamente en cada uno de los grupos no mostró diferencias (p=0.21)

Identification of Novel Genetic Markers of Breast Cancer Survival

Background: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. Methods: We conducted a large meta-analysis of studies in populations of European ancestry, including 37 954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200 000 and 900 000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23 059 ER-positive patients (1333 events). All statistical tests were two-sided. Results: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust. Conclusions: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors.Peer reviewe