Public Release: 

The role of obesity and calories in cancer prevention

Lifestyle changes may help prevent cancer

American Association for Cancer Research

Boston, MA (October 15, 2002) - Obesity, increasing at an alarming rate in the United States and in many other countries, is thought to result from lifestyle changes, including decreased physical activity and overconsumption of calories. Given these trends, as well as the link between obesity and cancer and several other chronic diseases, the development of intervention strategies that simultaneously prevent obesity and reduce cancer risk is critical. Several studies presented at the American Association for Cancer Research's (AACR) first annual Frontiers in Cancer Prevention Research meeting set the stage for further exploration into the connection between cancer and obesity.

Moderate Dietary Restriction Delays Breast Cancer
Prevention of obesity through dietary interventions, such as calorie restriction or occasional fasting, inhibits breast cancer growth, according to a study presented by researchers at the National Cancer Institute (NCI).

The study used mice with inherent alterations in two important and commonly altered genetic pathways in the human cancer process. Their mice were deficient in p53 (a tumor suppressor gene that acts like a brake to protect against uncontrolled cell proliferation) and also had high mammary gland expression of Wnt-1 (an oncogene that acts like an accelerator to enhance cell proliferation). Female p53-deficient Wnt-1 transgenic mice provided with unlimited access to food became obese and rapidly developed fatal mammary tumors, while mice provided with fewer calories each day, or fasted one day per week, lived tumor-free two to three times longer than the obese mice.

"Reduced serum levels of insulin-like growth factor (IGF)-1, which is a diet-responsive growth factor, were associated with the reduction in calorie intake and inhibition of mammary tumors in these mice" according to Stephen Hursting, Ph.D., deputy director of the Office of Preventive Oncology, Division of Cancer Prevention, NCI and lead investigator of the study. "These observations suggest that IGF-1 may be an important biological mediator of the protection afforded by the obesity-preventing interventions."

Hursting's group is currently testing whether exercise is effective in this model, and have recently observed that moderate treadmill exercise (about 30 minutes for five days a week) reduces fat mass and increases bone mineral density.

Method of Dieting May Play a Role in Prevention of Breast Cancer
A healthy diet combined with periods of calorie restriction may provide more protection against breast cancer than a constant low calorie diet, according to researchers at the Hormel Institute, University of Minnesota.

"The manner in which caloric restriction is implemented may play an important role in the development of breast cancer," according to Margot Cleary, lead investigator of the study. "There appears to be a point above which calorie intake stimulates the growth of breast cancer and can potentially override, to some degree, the protective effect of severe caloric restriction."

Mammary mouse tumor virus (MMTV)-TGFá mice (TGFá regulates growth) were fed either an ad lititum (as desired; AL), a calorie restricted (CR) or an intermittent caloric restriction/refeeding (IR-R) diet. The incidence of mammary tumors was 84 percent in AL mice, 37 percent for the CR mice, and 15 percent for the IR-R mice. Age of mammary tumor detection was significantly extended in the IR-R mice to 79.4 weeks of age compared to 67.9 weeks of age for AL mice. In addition, AL mice were younger at death than were both IR-R and CR mice.

Prepubertal Diet May Affect Future Breast Cancer Risk
A low fat diet rich in omega-3 fatty acids derived from fish oil, which may increase serum estradiol levels, alters the make-up of the mammary gland and reduces breast cancer risk, according to a study conducted by researchers at Georgetown University.

"The timing of estrogen exposure is essential in determining its effect on breast cancer risk," according to Dr. Leena Hilakivi-Clarke, professor of oncology and director of tumor biology, and lead investigator of the study. "Exposure to estrogen around puberty has been demonstrated to decrease the risk of developing breast cancer later in life; however, this is not an optimal chemoprevention method."

The study, designed to identify potential dietary methods to alter pre-puberty estrogen levels, compared low fat (16 percent energy) or high fat (39 percent energy) diets composed of either omega-3 or n-6 polyunsaturated fatty acids (PUFAs) in menhaden (fish) oil or corn oil, respectively, in nursing rats and their female offspring. Both the low and high fat fish oil diets increased circulating estrogen levels, but only the low fat diet reduced breast cancer risk.

Exercise May Maximize Benefits and Minimize Side Effects of Cancer Prevention Regimens
The combination of exercise and effective cancer prevention regimens can minimize the adverse side effects of cancer prevention interventions on bone health, according to NCI researchers. Calorie restriction (CR) is the most potent cancer prevention regimen in both spontaneous and chemically induced rodent tumor models. However, calorie restriction also decreases IGF-1 (insulin-like growth factor-1) levels by about 50 percent, thereby decreasing bone density (IGF-1 plays an important role in regulating aspects of development and aging such as bone density).

"These observations suggest that efforts to use CR or to target IGF-1 for cancer prevention could result in adverse effects on bone density," according to David Berrigan, Ph.D., cancer prevention and control fellow, NCI, and lead investigator of the study. "When using CR or IGF-1 for cancer prevention, measures must be included that minimize the negative effects on bone characteristics." According to the NCI's Hursting, "The issue of the effect of exercise on bone health is especially important when considering that osteoporosis is a significant health problem, particularly in older women who are also at high risk of breast cancer and who may be considering cancer preventive interventions."

More than 203,500 new cases of breast cancer will be diagnosed and more than 39,600 women will die in 2002, according to the American Cancer Society. Breast cancer is the second leading cause of cancer-related death in women.

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Founded in 1907, the American Association for Cancer Research (AACR) is a professional society of more than 19,000 laboratory and clinical scientists engaged in cancer research in the United States in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals (Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention).

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