The study is the first to suggest that a "negative energy balance" - produced by increasing the mice's energy output by use of a running wheel, while maintaining a restricted calorie intake - appeared to be the important factor in inhibiting the growth of polyps, which are the forerunners of colorectal tumors, says lead author Lisa H. Colbert, assistant professor in the UW-Madison department of kinesiology.
For the study, Colbert and her co-authors used mice with a genetic mutation that predisposed them to develop intestinal polyps.
"Our studies are relevant for humans in that these mice have a mutation in one of the same genes, APC, that is also mutated in human colon cancer," she explains. "The protective effect of exercise and lower body weight in our mice is consistent with epidemiological evidence in humans that suggests higher levels of activity and lower body weight reduces the risk of colon cancer." Mutations in the APC gene in humans are responsible for an inherited condition called familial adenomatous polyposis (FAP). This condition affects about one in 10,000-15,000 people worldwide, and 95 percent of those affected develop polyps in the colon that eventually progress into cancer, usually before age 40.
The researchers randomly assigned seven-week-old male mice to either voluntary wheel running or to no exercise for 10 weeks.
Over the course of the study, the no-exercise control group consumed as much food and water as they wanted. For the first three weeks, the exercising mice received as much as those in the control group. After that, the active mice were restricted to the amount of food and water that the control group received the previous week, which resulted in a negative energy balance.
By the end of the 10 weeks, six of the 23 control mice had died due to the number of polyps that had grown and the resulting anaemia, while all 24 exercising mice were still alive.
"The exercising mice ran an average of 3.8 km a day, and the further they ran the fewer polyps they had. Exercise significantly reduced total polyp number and polyp size, as well as prolonging survival," says Colbert. "On average, there were 16 polyps per mouse in the exercising mice compared to 22 polyps in the control mice - a decrease of 25 percent."
Even though the exercising mice weighed less than those in the control group at the end of the study, they retained more body fat than the non-exercising mice, which Colbert attributes to the fact that the exercising mice were healthier than the non-exercising mice.
The researchers also found that the exercising mice had higher levels of insulin-like growth factor-1 (IGF-1) and corticosterone - hormones associated with the onset of cancer - but saw no correlation with a greater numbers of polyps. Colbert explains, "These data suggest that voluntary exercise that induces a negative energy balance protects against the onset of cancer in these mice, but that the mechanism is unlikely to be related to body composition, IGF-1 or corticosterone."
Another study published in this issue of Carcinogenesis found that exercise can protect against skin cancer.
In this study, female mice that had 24-hour access to running wheels and were exposed to ultraviolet B light (UVB) took longer to develop skin tumors, developed fewer and smaller tumors, and had decreased amounts of body fat compared to mice that did not have access to running wheels. The researchers emphasized that it was unknown yet whether exercise decreased the risk of sunlight-induced skin cancer in humans, and clinical trials were needed to investigate this further.