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Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study.

ABSTRACT: BACKGROUND:Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL. METHODS:A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes. RESULTS:A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0-2.0; CDC: HR = 1.6, 95%CI:1.1-2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9-2.5; CDC: HR = 1.0; 95% CI:0.6-1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7-3.2; CDC: HR = 1.4; 95%CI:0.9-2.3) with early relapse were observed. CONCLUSIONS:Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment.

SUBMITTER: Nunez-Enriquez JC

PROVIDER: S-EPMC6639907 | biostudies-other | 2019 Jul

REPOSITORIES: biostudies-other

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Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study.

Núñez-Enríquez Juan Carlos JC Gil-Hernández Ana Elena AE Jiménez-Hernández Elva E Fajardo-Gutiérrez Arturo A Medina-Sansón Aurora A Flores-Lujano Janet J Espinoza-Hernández Laura Eugenia LE Duarte-Rodríguez David Aldebarán DA Amador-Sánchez Raquel R Peñaloza-González José Gabriel JG Torres-Nava José Refugio JR Espinosa-Elizondo Rosa Martha RM Flores-Villegas Luz Victoria LV Merino-Pasaye Laura Elizabeth LE Pérez-Saldivar María Luisa ML Dorantes-Acosta Elisa María EM Cortés-Herrera Beatriz B Solis-Labastida Karina Anastacia KA Núñez-Villegas Nora Nancy NN Velázquez-Aviña Martha Margarita MM Rangel-López Angélica A González-Ávila Ana Itamar AI Santillán-Juárez Jessica Denisse JD García-Velázquez Alejandra Jimena AJ Jiménez-Morales Silvia S Bekker-Méndez Vilma Carolina VC Rosas-Vargas Haydee H Mata-Rocha Minerva M Sepúlveda-Robles Omar Alejandro OA Martín-Trejo Jorge Alfonso JA Mejía-Aranguré Juan Manuel JM

BMC cancer 20190718 1

<h4>Background</h4>Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL.<h4> ...[more]

PMID: 31319816

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Project description:The objective of the study was to provide current estimates of the prevalence and trends of overweight and obesity (OW+OB) in Mexican children and adolescents.Body mass index objectively measured was analyzed for 37?147 children and adolescents aged 0-19 years obtained in 2012 as part of the National Health and Nutrition Survey (ENSANUT-2012), a nationally representative sample of the Mexican population. In addition, data from previous National Nutrition Surveys obtained in 1988, 1999 and 2006 were compared with analyze trends over a 24-year period (1988-2012) for children <5 years of age and adolescents and over a 13-year period (1999-2012) for school-age children. World Health Organization Child Growth Standard was used to define OW+OB.In 2012, 33.5% of children <5 years of age (both sexes) were at risk of overweight or were overweight (OW); 32% and 36.9% of girls and boys 5-11 years of age were OW+OB, respectively, and 35.8% and 34.1% of female and male adolescents were OW+OB, respectively. Statistically significant trends were documented for all age groups during the study period. Overall change in the combined prevalence in preschool children was 6.3±1.0 percentage points (pp; P<0.001; 0.26 pp per year) in the last 24 years, showing the highest increase between 1988 and 1999, whereas for school-age girls (from 1999 to 2012) and adolescent females (from 1988 to 2012), OW+OB increased across all periods at a declining trend, with an overall change of 0.5 and 1.0 pp per year, respectively. Changes in the prevalence of OW+OB were highest among children and adolescents in the lowest quintile of the household living condition index.Prevalence of OW+OB among children and adolescents increased significantly during the last 13-24 years. The rate of increase has declined in the last 6 years in all age groups. Changes in prevalence of OW+OB presented here suggest that, in Mexico, the burden of obesity is shifting toward the groups with lower socioeconomic level.

Project description:Background and aims: Youth populations with overweight/obesity (OW/OB) exhibit heterogeneity in cardiometabolic health phenotypes (e.g. fasting glucose, serum triglycerides, etc.). The underling mechanisms for those differences are still unclear. This study aimed to analyze the whole blood transcriptome profile (RNA-seq) of children with metabolic healthy overweight/obesity (MHO) and metabolic unhealthy overweight/obesity (MUO) phenotypes. Methods: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were included. MHO was defined as having none of the following criteria for metabolic syndrome: elevated fasting glucose, high serum triglycerides, low high-density lipoprotein cholesterol, and high systolic or diastolic blood pressure, while MUO was defined as presenting one or more of these criteria. Inflammatory markers interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF) and, vascular endothelial growth factor A (VEGF) were additionally determined. Total-blood RNA was analyzed by 5’-end RNA sequencing. Two different bioinformatics approaches were performed: 1) Differential gene expression analyses using Limma R/Bioconductor software package (analyses adjusted by sex and maturational status) and 2) weighted gene coexpression network analyses (WGCNA). Results: Children with MHO had lower values of pro-inflammatory cytokines TNF-α and IL-6 compared to MUO (p < 0.05). 40 genes were differentially expressed (FDR < 0.05) in children with MHO compared to MUO. WGCNA analysis identified 23 gene coexpression modules (i.e. clusters of genes) with low preservation (Zsummary < 2) in children with MHO compared to MUO. Differential and WGCNA gene expression patterns identified 32 genes linked to metabolism, mitochondrial and immune functions. Conclusions: Whole blood transcriptome analysis revealed a distinct pattern of gene expression in children with MHO compared to MUO children. The identified gene expression patterns related to metabolism, mitochondrial and immune functions can promote a better understanding of cardiovascular disease prognosis in individuals with MHO.

Project description:Background: The current knowledge about the molecular mechanisms underlying the health benefits of exercise is still limited, especially in the pediatric population. We set out to investigate the effect of a 20-week exercise intervention on whole blood transcriptome profile (RNA-seq) in children with overweight/obesity. Methods: Twenty-four pre-pubertal children (10.21 ± 1.33 years, 46% girls) with overweight/obesity, were randomized to either a 20-week exercise program (intervention group; n=10), or to a non-exercise control group (usual lifestyle, n=14). Whole blood transcriptome profile was analysed using RNA-seq STRT2 technique. Gene expression analysis was carried out with the Limma R/Bioconductor software package, and the gene ontology (GO) and pathway enrichment analyses were performed using R. Ingenuity Pathway Analysis (IPA) was performed for gene network detection. The transcriptome data were in silico validated using PHENOPEDIA and meta-analysis database extrameta.org. Results: 161 genes were differentially expressed between the exercise and the control groups among boys, and 121 genes among girls (p-value < 0.05), while after multiple correction, no significant difference between groups persisted in gene expression profiles (FDR > 0.05). Based on non-corrected analyses, the enriched GO processes and molecular pathways highlighted the effect of exercise on different immune response related pathways in boys (antigen processing and presentation, infections, and T cell receptor complex) and girls (Fc epsilon RI signaling pathway) (FDR < 0.05). In silico data mining and validation analyses (using PHENOPEDIA and meta-analysis database extrameta.org) highlight top genes regulated by exercise such as CD6, HLA-C, TNFRSF1A, MYD88, and NFKBIA genes in boys and RAC1, ANXA6, FYN, INPP5D, PIK3CD and SPARC genes in girls. Conclusion: These results suggest that 20-week exercise program influences different immune processes in children with overweight/obesity. The transcriptome differences between boys and girls could partly be explained, in addition to the gender differences, by the distinct intensity in the exercise intervention as boys had stronger exercise stimulus in training. Our findings should be considered exploratory and preliminary given the relatively small sample size. Larger and more powered randomized controlled trials should confirm or contrast our findings.

Dataset Information

Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study.

Publications

Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study.

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