Weight Loss in Overweight and Obese People May Lower Levels of Certain Proteins Linked to Cancer


Key Points

  • Overweight or obese postmenopausal women who lost weight through diet and exercise significantly lowered their levels of circulating VEGF, PAI-1, and PEDF proteins, which play a role in angiogenesis.
  • Weight loss in overweight or obese individuals may reduce their risk for developing cancer in part through altering angiogenesis.
  • Weight loss could provide an incentive for reducing weight as a cancer prevention strategy in overweight and obese individuals.

A new study investigating the effects of dietary weight loss and exercise on circulating levels of certain angiogenesis-related proteins, including vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), and pigment epithelium-derived factor (PEDF), in postmenopausal overweight and obese women has found that weight loss significantly lowered the levels of these proteins. Reported by Duggan et al and published in Cancer Research, these findings suggest that weight loss could provide an incentive for reducing weight as a cancer prevention strategy in overweight and obese individuals.

Study Methodology

Researchers from the Fred Hutchinson Cancer Research Center in Seattle recruited 439 healthy postmenopausal, overweight (body mass index of > 25 kg/m2), sedentary women, aged 50 to 75. The women were not taking hormone replacement therapy. Participants were enrolled in the study between 2005 and 2008, and a 12-month follow-up for all participants was completed in 2009.

The participants were randomized to a four-arm trial comparing a caloric-restriction diet arm of no more than 2,000 kcal/d that included less than 30% of fat calories (goal: 10% weight loss, n = 118); aerobic exercise arm (225 min/wk of moderate-to-vigorous activity (n =117); a combined diet-and-exercise arm (n = 117); or a control arm (no intervention; n = 87) on circulating levels of angiogenic biomarkers.

VEGF, PAI-1, and PEDF were measured by immunoassay at baseline and at 12 months. Changes were compared using generalized estimating equations, adjusting for baseline body mass index, age, and race/ethnicity.

Study Findings

The researchers found that participants randomized to the diet-plus-exercise arms had statistically significantly greater reductions in PAI-1 at 12 months compared with controls (–19.3% vs +3.48%, respectively, P < .0001). Participants randomized to the diet and diet-plus-exercise arms had statistically significantly greater reductions in PEDF (–9.20%, –9.90%, respectively, both P < .0001) and VEGF (–8.25%, P = .0005; –9.98%, P < .0001, respectively) compared with controls.

There were no differences in any of the analytes in participants randomized to the exercise arm compared with controls. Increasing weight loss was statistically significantly associated with linear trends of greater reductions in PAI-1, PEDF, and VEGF.

“We know that being overweight and having a sedentary lifestyle is associated with an increase in risk for developing certain types of cancer. However, we don’t know exactly why,” said Catherine Duggan, PhD, Principal Staff Scientist in the Public Health Sciences Division at the Fred Hutchinson Cancer Research Center and first author of this study, in a statement. “Our study shows that weight loss is a safe and effective method of improving the angiogenic profile in healthy individuals. We were surprised by the magnitude of change in these biomarkers with weight loss. While we can’t say for certain that reducing the circulating levels of angiogenic factors through weight loss would impact the growth of tumors, it is possible that they might be associated with a less favorable milieu for tumor growth and proliferation.”

“Weight loss reduced circulating VEGF, PEDF, and PAI-1, suggesting that weight loss in overweight or obese postmenopausal women may reduce risk for cancer in part through altering angiogenesis. Further investigations into the unexpected reductions of PEDF levels with weight loss are warranted,” concluded the study authors.

The study authors reported no potential conflicts of interest.

Funding for this study was provided by the National Cancer Institute and the Breast Cancer Research Foundation.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.