Study to determine if obesity, caloric restriction affect colon cancer
Susan Olivo-Marston, assistant professor in the Division of Epidemiology, recently received a grant from the Ohio State Center for Advanced Functional Foods Research and Entrepreneurship (CAFFRE) and the OSUCCC-James Molecular Carcinogenesis and Chemoprevention Diet, Nutrition, and Cancer Research Program. Her study is titled, “The effects of caloric-restriction and obesity on the initiation and promotion of colon carcinogenesis in an azoxymethane-induced murine model.”
Olivo-Marston hopes to learn whether obesity can increase risk and progression of colon cancer, and alternatively, whether a restricted-calorie diet can reduce risk and progression.
“The award will allow me to expand my current NCI-funded study to examine not only how early-onset obesity may contribute to adult colon cancer risk, but also how energy (or caloric) restriction may protect against colon cancer risk,” Olivo-Marston said. “It also allows us to examine every possible combination of obesity versus energy restriction during the life course.
“For example, we will examine whether lifetime energy restriction is more protective than energy restriction during just childhood or just adulthood. We will also be able to examine whether restriction early in life conveys any protection when followed by obesity during adulthood. We are really excited for the expansion of this project.”
The grant focuses on early-onset obesity. Olivo-Marston is modeling in mice what will happen in humans who are obese as children. Half of the grant is an animal study, and the other half is a population-based study with data from the Women’s Health Initiative.
Because the data is only from females, the research is focused on female mice. The center contains data from nearly 2,000 women who developed colon cancer, including height, weight, blood samples, and measurements of certain biomarkers associated with colon cancer. Olivo-Marston and her research team are looking at many of the same biomarkers in mice, and will use the data to find correlations between the two populations.
Starting at the time the mice are 21 days, the mice are started on a high-fat diet that closely resembles what a person may eat.
“We have one arm that starts right when they’re weaned—the early obesity group-- then I added a group that had their calories restricted at the same time point, reducing them by 30 percent compared to the control group,” Olivo-Marston said. “There’s a lot of data looking at calorie restriction in cancer as well as obesity, but the data shows that calorie restriction may have beneficial effects. I was interested in seeing if we could restrict their calories early on to see if that would have a long-term effect.”
The mice go through dietary intervention for approximately 10 weeks. At that point, most are placed back on a regular diet, but one group stays on a high fat diet. That group models humans becoming obese and staying obese. The study uses 250 mice total, but started with a test group of 50. All 50 have gone through the 10 weeks of the diet, and the group that was on a high fat diet had a higher body weight, and the group with restricted calories had a drop in weight.
The mice are injected with a colon cancer-specific carcinogen once per week for six weeks. “We’ll follow them after that and see what effect the high fat diet has,” Olivo-Marston said.
“Do the mice that are staying obese develop tumors sooner? Are they bigger? Are there more of them? Are they more aggressive? We have a lot of potential end points that we’ll be looking at; the major one being focusing on the development of colon tumors and seeing if those mice on the high fat diet have more. I’m interested to see if the mice that were on a low calorie diet have any kind of protection from that.”
The study, which started in August, will take about nine months from beginning to end. The team anticipates following the mice until they reach 41 weeks of age.
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