Obesity and metabolic dysfunction increase the risk of cancer incidence and mortality. Increases in obesity and associated metabolic dysfunction are likely partly attributable to modern lifestyles haracterized by high fat food intake and reduced physical activity, and such behaviors may begin in childhood. Insufficient sleep, increasingly common in adolescents, has been implicated as a risk factor for both obesity and metabolic dysfunction. In this project, we will define the relationship between a number of host risk factors operating during childhood and adolescence, including insufficient sleep and sleep apnea, to longitudinally measured changes in both weight and biochemical indices of metabolic pathways implicated in cancer. We will capitalize on access to a large population-based pediatric cohort, the Cleveland Children's Sleep and Health Study, in which multiple measures of behavioral, sleep and biochemical risk factors for obesity have been measured longitudinally. The sample includes 50% former preterm children and 41% ethnic minorities, providing opportunities to quantify and identify specific mediators of excess risk of obesity and metabolic dysfunction in vulnerable subgroups. We propose to study 600 cohort members at ages 16 to 19 years, obtaining current measures of metabolic function that have been implicated in cancer (i.e., sex hormone levels, insulin resistance, adipokines, growth factors). Anthropmetric measurements will quantify body weight, stature, and body fat distribution. Risk factor data include standardized assessments of nutritional intake and behavioral risk factors. Subjects also will undergo 5-7 day monitoring of physical activity level and sleep/wake behavior with actigraphy and an overnight sleep study. Combining these data with birth data and data collected at a previous 8 to 11 year old exam will allow us to address the hypothesis that weight gain is largest in adolescents with insufficient sleep, and such effects are independent of other behavioral risk factors; and that metabolic dysfunction is most marked in adolescents with sleep apnea and in those with rapid weight gain. Identification of risk factors for obesity and metabolic dysfunction, and their variation with demography and common behavioral factors, including the novel consideration of sleep behaviors, may help develop targeted interventions for high-risk children and elucidate important pathophysiological pathways that increase risk of several chronic health conditions, including cancer and diabetes.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1)
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Case Western Reserve University
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Doerner, Stephanie K; Reis, Edimara S; Leung, Elaine S et al. (2016) High-Fat Diet-Induced Complement Activation Mediates Intestinal Inflammation and Neoplasia, Independent of Obesity. Mol Cancer Res 14:953-965
Feng, Zhaoyang; Hanson, Richard W; Berger, Nathan A et al. (2016) Reprogramming of energy metabolism as a driver of aging. Oncotarget 7:15410-20
Yuan, Yiyuan; Hakimi, Parvin; Kao, Clara et al. (2016) Reciprocal Changes in Phosphoenolpyruvate Carboxykinase and Pyruvate Kinase with Age Are a Determinant of Aging in Caenorhabditis elegans. J Biol Chem 291:1307-19
Noy, Noa; Li, Li; Abola, Matthew V et al. (2015) Is retinol binding protein 4 a link between adiposity and cancer? Horm Mol Biol Clin Investig 23:39-46
Abola, Matthew V; Thompson, Cheryl L; Chen, Zhengyi et al. (2015) Serum levels of retinol-binding protein 4 and risk of colon adenoma. Endocr Relat Cancer 22:L1-4
Spilsbury, James C; Storfer-Isser, Amy; Rosen, Carol L et al. (2015) Remission and incidence of obstructive sleep apnea from middle childhood to late adolescence. Sleep 38:23-9
Hibbs, Anna Maria; Storfer-Isser, Amy; Rosen, Carol et al. (2014) Advanced sleep phase in adolescents born preterm. Behav Sleep Med 12:412-24
Gharib, Sina A; Seiger, Ashley N; Hayes, Amanda L et al. (2014) Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes. Sleep 37:709-14
Ochs-Balcom, Heather M; Vaughn, Caila B; Nie, Jing et al. (2014) Racial differences in the association of insulin-like growth factor pathway and colorectal adenoma risk. Cancer Causes Control 25:161-70
Boeke, Caroline E; Storfer-Isser, Amy; Redline, Susan et al. (2014) Childhood sleep duration and quality in relation to leptin concentration in two cohort studies. Sleep 37:613-20

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