Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis
Final rept. 1 Jun 2013-31 May 2015
NORTH CAROLINA UNIV AT CHAPEL HILL
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Obesity is associated with increased risk and worse outcomes for ovarian cancer OC. We theorize that the metabolic effects of obesity may play a contributing role in the pathogenesis of OC and lead to biologically different cancers than those that arise in normal weight women. We also posit that the timing and length of the obesity exposure may be critical in the development of obesity-driven OCs. We have demonstrated that adulthood exposure to obesity can promote tumor progression, as evidenced by a tripling in tumor size, in the KpB mouse model of serous OC. The ovarian tumors that arose in the obese mice were genomically and metabolically different from those that arose in lean mice. To expand on this work, we assessed in utero, adolescent and adulthood exposure to obesity as well as cross-over between these timeframes in the KpB mice. Obesity during adolescence and adulthood had a greater influence on tumor aggressiveness, as measured by increasing tumor size, than in utero exposure to obesity alone. Using The Cancer Genome Atlas database, we compared the gene expression between OCs from normal weight versus overweightobese women. Metabolically relevant alterations in gene expression were found in relationship to BMI among serous OCs.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research