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Cancer Control Research

Abstract

DESCRIPTION (provided by applicant): Treatment for acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, involves 24 to 36 months of chemotherapy and high dose steroids. Additionally, cranial radiation is sometimes included for treatment or prevention of central nervous system involvement. The 5-year survival probability of childhood is all over 80%, and there are tens of thousands of adult survivors worldwide. These individuals have a higher than expected frequency of obesity and early mortality from cardiovascular disease. Childhood ALL survivors may also be at increased risk for the metabolic syndrome, a constellation of disorders characterized by central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension. The syndrome is clearly associated with substantially elevated risks for type 2 diabetes mellitus and atherosclerotic coronary disease. Deficiency in growth hormone secretion, which can result from damage to the hypothalamic-pituitary axis from either chemotherapy or cranial radiation, has been implicated in the pathogenesis of metabolic syndrome in childhood cancer survivors. 75 adult survivors of childhood ALL, ages 18-49 years will be randomly selected and recruited from an ongoing epidemiologic study to participate in a 2-day clinical evaluation. The aims of this study are to: 1) compare the extent to which prevalence of the metabolic syndrome is higher in ALL survivors than in same age, same sex population norms; 2) evaluate the relation between growth hormone deficiency and the metabolic syndrome; 3) investigate whether endothelial impairment and other early signs of cardiovascular disease are more prevalent among ALL survivors with, versus without, the metabolic syndrome; and 4) compare whether adjuvant cranial radiation increases risk for the metabolic syndrome above that of chemotherapy alone. A comparative evaluation of health behaviors and health knowledge related to diabetes, cardiovascular disease, physical activity, and nutrition, and will also be included in the study. This proposal addresses the great need for clinical research on long-term, adverse effects of childhood cancer and its treatment, particularly those that are preventable or modifiable. The study will provide important data on potential etiologic factors, such as growth hormone deficiency and cranial radiation, and on potential avenues for education and intervention, such as targeted modifications of physical activity and dietary habits.