All ETDs from UAB

Advisory Committee Chair

Tim R Nagy

Advisory Committee Members

Ronald D Alvarez

Pi-Ling Chang

Barbara A Gower

Gary R Hunter

Document Type

Dissertation

Date of Award

2010

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

Obesity increases the risk for breast and endometrial cancers while weight loss reduces the risk for these cancers. One aim of this dissertation was to determine the effects of weight loss from an overweight state [body mass index (BMI) 27-30] to a normal weight state on several obesity-related cancer biomarkers in African-American (AA) and European-American (EA) premenopausal women. We also sought to determine whether the method of weight loss, caloric restriction alone (CR) or combined with exercise resulted in similar changes in cancer biomarkers. The biomarkers of interest were urinary estrogen metabolites, and serum adiponectin, leptin, insulin-like growth factor (IGF)-1, IGF binding protein (BP)-1 and sex hormone binding globulin (SHBG). With the exception of total IGF-1, weight loss significantly modified all biomarkers reflecting the anti-carcinogenic characteristics of a leaner phenotype. The change in biomarkers was similar among the three weight loss groups. Further, we discovered that race was an important factor in determining the concentrations of several biomarkers, independent of adiposity. In addition to investigating the change in several individual biomarkers, we explored whether weight loss resulted in overall changes in sera that reduced cellular proliferation and increased apoptosis in vitro and whether there were differences in these parameters among the groups. We found that cells grown with post- weight loss sera were less proliferative relative to cells grown in sera from the same women in the pre weight loss state. The sera from the CR weight loss group tended to be less proliferative relative to other weight loss groups. There was no difference in apoptosis in cells grown in sera from post weight loss state compared to cells grown with sera from pre weight loss state. In conclusion, weight loss, irrespective of the method, modified several cancer biomarkers although CR alone may be a more effective method to reduce cellular proliferation. Racial differences exist in the concentrations of cancer biomarkers and may partially explain the disparities seen in cancer outcomes. Weight loss should be promoted as a method to reduce the risk for breast and endometrial cancers.

Share

COinS