Abstract 4104: Obesity and colon cancer: Does time of exposure matter

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Purposes: Obesity is associated with an increased risk of colon cancer in many epidemiology studies, while calorie restriction (CR) has shown protective effects on colon tumorigenesis in animal studies. This preclinical study was designed to investigate the long-term impacts of early exposure to high fat diet or CR diet on colon tumorigenesis. Methods: 50 three-week-old female C57/B6J mice were assigned into five groups: 1) control; 2) HF-control; 3) control-HF; 4) HF and 5) CR-control. Mice were initially placed on a control diet (10% kcal from fat), HF diet (45% kcal from fat), or 30% CR diet and fed ad libitum for nine weeks from the time of weaning and followed by a seven-week control diet. Azoxymethane was injected once a week for five weeks at a dose of 10 mg/kg beginning at 13 weeks of age. At 18 week-old, mice were placed on either a control diet or a HF diet. Mice were euthanized at 46 week-old and colons were collected to assess tumorigenesis. Results: After nine weeks of diet intervention, the percentage of body fat was higher in the mice on the HF diet (31.9%) and lower in those on the CR diet (18.4%), compared to mice on the control diet (20.0%, p=0.08). Mice on a CR diet in early life had lower body weights at the endpoint, compared to those on the control diet (p=0.03). Analysis of colon histopathology is ongoing as well as evaluation of apoptosis and proliferation. Conclusions: Early life exposure to calorie restriction has long-term impacts on body weight. Early life exposure to high fat diet may increase the risk of colon tumorigenesis. This model is currently being used to investigate the effects of early alterations in energy balance on colon cancer development and underlying molecular mechanisms. Citation Format: Jinyu Xu, Jennifer Thomas-Ahner, Samantha DeMarsh, Steven K. Clinton, Susan E. Olivo-Marston. Obesity and colon cancer: Does time of exposure matter. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4104. doi:10.1158/1538-7445.AM2014-4104