Obesity Increases Risk of Cancers in Mice
Conquest - Summer 2008
By Scott Merville
Evidence showing the benefits of calorie-restricting diets builds as two teams of M. D. Anderson researchers discovered that low-fat and low-calorie diets in mice inhibited further development of precancerous growths in pancreatic and epithelial skin cancers.
John DiGiovanni, Ph.D., director of the Department of Carcinogenesis and of M. D. Anderson’s Science Park-Research Division, and graduate student Tricia Moore found that a calorie-restricted diet reduced precancerous skin lesions in mice. They also learned that calorie restriction inhibits two molecular pathways involved in tumor development.
Pancreatic cancer study
“Our findings indicate that a restricted-calorie diet hinders development of pancreatic cancer, which could have implications for prevention and treatment of pancreatic tumors caused by chronic inflammation and obesity,” says senior author on the pancreatic study Stephen Hursting, Ph.D., professor in M. D. Anderson’s Department of Carcinogenesis and chair of the Division of Nutritional Sciences at The University of Texas at Austin.
In the pancreatic cancer study, a special strain of mice was bred that spontaneously developed precancerous pancreatic lesions, says co-author Sue Fischer, M.D., professor in the Department of Carcinogenesis.
Each mouse was fed one of the following diets:
- A high calorie diet with 60% of calories from fat to produce obese mice;
- A control diet with 10% of calories from fat to produce overweight mice;
- A calorie-restricted diet with 30% fewer calories than control to produce lean mice.
Mice receiving the calorie-restricted diet developed fewer and less severe pancreatic lesions after four months, while the mice on the obesity diet developed more severe lesions.
Epithelial cancer study
Epithelial cancers develop in the epithelium, the tissue that lines the surfaces and cavities of the body’s organs and account for 80% of all cancers.
“Therefore, results of the epithelial skin cancer study are broadly applicable to epithelial cancers in other tissues,” says John DiGiovanni, Ph.D., senior author on the skin cancer study and the director of M. D. Anderson’s Department of Carcinogenesis and the Science Park-Research Division in Smithville, Texas.
Mice were given agents to make them develop papillomas (precancerous skin lesions) and were fed either a high-calorie diet, control diet or calorie-restricted diet.
Mice on calorie-restricted diets formed significantly fewer papillomas than mice on the other diets.
A separate study assessed the effects of these high- and low-calorie diets on the development of papillomas, as well as the conversion of papillomas to squamous cell carcinomas (malignant skin cancers). It showed calorie intake affects the prevalence of papillomas, but it does not influence the rate at which papillomas become cancerous.
Further research has identified two important signaling pathways within epithelial cells that mediate many of the effects of calorie restriction on tumor development.
Previous research has suggested that a chronically positive energy balance (consuming more calories than are needed for the energy expended) can lead to obesity and increased risk of several cancers. On the other hand, DiGiovanni says, maintaining a negative balance (such as with a calorie-restricted diet) often decreases cancer risk.
Hursting states that the impact of calorie intake on pancreatic cancer has not been well studied, and the mechanisms underlying the calorie-cancer connection are unknown.
The findings of both studies provide the basis for additional research regarding the prevention of tumors caused by cancers related to diet and obesity.
Conquest - Summer 2008