Fat, hormones, and cancer
Exactly how excessive body fat heightens the risk of cancer is a complex and still-unfolding story, with many players under suspicion. Weight gain produces changes in the body's metabolism, and one result is an increase in the bloodstream of growth-promoting hormones such as estrogen, insulin, insulin-like growth factor-1 (IGF-1), and leptin. High levels of these hormones may help jump-start the abnormal growth and proliferation of normal cells that results in cancer.
Dana-Farber President Ed Benz, MD, says keeping a healthy weight helps reduce cancer risk.
Elevated levels of IGF-1, for example, raise the odds of developing prostate cancer in men and premenopausal breast cancer in women. Heightened IGF-1 has also been linked to pancreatic, colorectal, and lung cancer. Fuchs and his colleagues are evaluating levels of IGF-1 and insulin in patients with pancreatic, colon, and other gastrointestinal cancers, where they've been implicated as factors.
"It's not just the body mass index we're interested in, but the increase in insulin," says Fuchs. "So we're creating a 'dietary insulin index' to see which foods make your insulin go up." Ultimately, this research could benefit early diagnosis and prevention of some cancers, he says.
Bruce Spiegelman, PhD, a Dana-Farber investigator who has made many discoveries about the regulation of fat cell development, blood sugar production, and diabetes, believes it's too early to exclude any biochemical suspects in the obesity-cancer connection. "I don't think the evidence is good enough yet," he says. "But if I had to bet on one thing, I'm suspicious about the elevated levels of lipids [fatty substances] in the blood of obese people."
Spiegelman's priority is to create a good animal model of obesity. Mice that are genetically prone to being severely overweight do exist, but Spiegelman says that they don't accurately represent the condition in humans. Once researchers have an acceptable rodent model, they can begin to sort out the biochemical pathways leading from excess body fat to cancer—and can test an array of potential ways to block these pathways. "I think we can do this work at a state-of-the-art level," says Spiegelman confidently. "And Dana-Farber is well-positioned to be a leader in this area."
For more information on the study of insulin levels in breast cancer, contact Taylor Salinardi at (617) 632-5934.
