Researchers at The University of Texas M. D. Anderson Cancer Center, have found a link between dietary balance and common cancer pathways and say that a restricted-calorie diet inhibits skin cancer while obesity triggers it.
The study led by Tricia Moore, a graduate student in M. D. Anderson's Department of Carcinogenesis, asserted that while calorie-restriction inhibited the development of precancerous growths in a two-step model of skin cancer, reducing the activation of two signalling pathways known to contribute to cancer growth and development, on the other hand obesity-inducing diet activated those pathways.
"These results, while tested in a mouse model of skin cancer, are broadly applicable to epithelial cancers in other tissues," said John DiGiovanni senior author of the study.
Epithelial cancers originate in the epithelium - the tissue lining the surfaces and cavities of the body's organs and comprise 80 percent of all cancers.
"Calorie restriction and obesity directly affect activation of the cell surface receptors epidermal growth factor (EGFR) and insulin-like growth factor (IGF-1R). These receptors then affect signaling in downstream molecular pathways such as Akt and mTOR. Calorie restriction, which we refer to as negative energy balance, inhibits this signaling, and obesity, or positive energy balance, enhances signaling through these pathways, leading to cell growth, proliferation and survival," said Moore.
Dietary energy implies to the relationship between caloric intake and energy expenditure. DiGiovanni said that as suggested by earlier studies, chronic positive energy balance, which can lead to obesity, increases the risk of developing a variety of cancers, while negative balance often decreases risk.
In the study, the researchers employed four diets, two representing calorie reductions of 30 percent and 15 percent, a control diet including 10 percent kilocalories from fat, and an obesity-inducing diet consisting of 60 percent kilocalories from fat. Later mice were given agents to induce premalignant lesions called papillomas, which are precursors to cancer.
It was discovered that those on the calorie restricted diets had considerable inhibition of papilloma formation compared with the other two diets.
In another study it was shown that dietary energy balance decides the number of carcinomas found through its effects on the number of premalignant lesions but does not affect the rate of malignant conversion. While Akt and mTOR pathways were found to be significant in this model, increased Akt and mTOR signaling are linked to the growth, proliferation and survival of many human cancers.
"These findings provide the basis for future translational studies targeting Akt/mTOR pathways through combinations of lifestyle and pharmacologic approaches to prevent and control obesity-related epithelial cancers in humans," said DiGiovanni.
The study was presented at the American Association for Cancer Research annual meeting.