Childhood cancer incidence and survival in Thailand: A comprehensive population‐based registry analysis, 1990–2011

BackgroundSoutheast Asia is undergoing a transition from infectious to chronic diseases, including a dramatic increase in adult cancers. Childhood cancer research in Thailand has focused predominantly on leukemias and lymphomas or only examined children for a short period of time. This comprehensive multisite study examined childhood cancer incidence and survival rates in Thailand across all International Classification of Childhood Cancer (ICCC) groups over a 20‐year period.MethodsCancer cases diagnosed in children ages 0‐19 years (n = 3574) from 1990 to 2011 were extracted from five provincial population‐based Thai registries, covering approximately 10% of the population. Descriptive statistics of the quality of the registries were evaluated. Age‐standardized incidence rates (ASRs) were calculated using the Segi world standard population, and relative survival was computed using the Kaplan‐Meier method. Changes in incidence and survival were analyzed using Joinpoint Regression and reported as annual percent changes (APC).ResultsThe ASR of all childhood cancers during the study period was 98.5 per million person‐years with 91.0 per million person‐years in 1990–2000 and 106.2 per million person‐years in 2001–2011. Incidence of all childhood cancers increased significantly (APC = 1.2%, P < 0.01). The top three cancer groups were leukemias, brain tumors, and lymphomas. The 5‐year survival for all childhood cancers significantly improved from 39.4% in 1990–2000 to 47.2% in 2001–2011 (P < 0.01).ConclusionsBoth childhood cancer incidence and survival rates have increased, suggesting improvement in the health care system as more cases are identified and treated. Analyzing childhood cancer trends in low‐ and middle‐income countries can improve understanding of cancer etiology and pediatric health care disparities.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146559/1/pbc27428_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146559/2/pbc27428.pd

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Disparities in Environmental Exposures and Health in Thailand: Molecular Effects of Chronic Cadmium Exposure and Trends in Childhood Leukemia

Thailand has undergone rapid social and economic changes over the past fifty years, and prevalence and mortality of disease has decreased for infectious diseases and increased for chronic diseases across the age spectrum. This dissertation focuses on identifying disparities in childhood cancer and environmental health in Thailand by examining 1) childhood leukemia incidence and survival trends from 1990-2011 in the Songkhla Province in Thailand, and 2) high cadmium (Cd) exposure among northern Thai women from Mae Sot and its effects on biologic aging and co-exposure to toxic and essential metals. The first aim utilized cancer data from the Songkhla Cancer Registry and the United States (US). Leukemia incidence and survival was significantly lower in Songkhla compared to US but incidence and survival significantly increased annually from 1990-2011 in Thailand by approximately 2%. In the second and third aims, epigenome-wide DNA methylation and blood and urine metal biomarkers of exposure were measured in two samples of women from Mae Sot. These women were exposed to Cd, a toxic metal, after ingesting water and rice contaminated by environmental pollution from nearby zinc mining. DNA methylation is a dynamic and sensitive epigenetic marker that changes during aging and is associated with Cd exposure. Biologic age, or the physiologic age of an individual, can be estimated from a collection of a subset of these changes. A greater difference between chronologic age and biologic age may indicate accelerated aging. In Aim 2, higher Cd exposure was associated with smaller difference between biologic and chronologic age, and Cd modified methylation at some age-associated sites included in predictors of biologic age. In Aim 3 co-exposure of metals were examined in blood and urine using multivariate methods. Blood lead and urinary arsenic were also elevated in this high Cd exposed sample. Unique patterns emerged among these metals, suggesting that lead and Cd exposures were independent. Further public health interventions are necessary to address pediatric cancer incidence and survival disparities in Thailand and to study sources of exposure to other metals and other biomarkers aging within the Mae Sot population.PHDEnvironmental Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135800/1/kdemanel_1.pd

Differences in childhood leukemia incidence and survival between Southern Thailand and the United States: a population‐based analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113128/1/pbc25571.pd

Childhood cancer incidence and survival in Thailand: A comprehensive population-based registry analysis, 1990–2011

Background: Southeast Asia is undergoing a transition from infectious to chronic diseases, including a dramatic increase in adult cancers. Childhood cancer research in Thailand has focused predominantly on leukemias and lymphomas or only examined children for a short period of time. This comprehensive multisite study examined childhood cancer incidence and survival rates in Thailand across all International Classification of Childhood Cancer (ICCC) groups over a 20-year period. Methods: Cancer cases diagnosed in children ages 0-19 years (n = 3574) from 1990 to 2011 were extracted from five provincial population-based Thai registries, covering approximately 10% of the population. Descriptive statistics of the quality of the registries were evaluated. Age-standardized incidence rates (ASRs) were calculated using the Segi world standard population, and relative survival was computed using the Kaplan-Meier method. Changes in incidence and survival were analyzed using Joinpoint Regression and reported as annual percent changes (APC). Results: The ASR of all childhood cancers during the study period was 98.5 per million person-years with 91.0 per million person-years in 1990–2000 and 106.2 per million person-years in 2001–2011. Incidence of all childhood cancers increased significantly (APC = 1.2%, P \u3c 0.01). The top three cancer groups were leukemias, brain tumors, and lymphomas. The 5-year survival for all childhood cancers significantly improved from 39.4% in 1990–2000 to 47.2% in 2001–2011 (P \u3c 0.01). Conclusions: Both childhood cancer incidence and survival rates have increased, suggesting improvement in the health care system as more cases are identified and treated. Analyzing childhood cancer trends in low- and middle-income countries can improve understanding of cancer etiology and pediatric health care disparities