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

Abstract

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.