Obesity is a risk factor for several types of cancer, including postmenopausal breast cancer and endometrial cancer. With the ongoing global obesity epidemic as well as cancer being the second leading cause of death worldwide, there is considerable interest in understanding the link between excess fat and cancer risk. A number of mechanisms through which obesity increases the risk for cancer have been proposed, including systemic inflammation, elevated insulin, elevated sex hormones, and adipose tissue-secreted signaling factors. Obesity may also influence angiogenesis, the biological process of new blood vessel formation, which is required to accommodate adipose tissue expansion. An increased concentration of circulating angiogenic factors associated with obesity may be a mechanism through which tumors grow and expand as tumors require an ‘angiogenic switch’ to develop beyond their initial non-invasive state. Researchers from Dr. Anne McTiernan’s group in the Public Health Sciences Division recently published a paper in Cancer Epidemiology, Biomarkers & Prevention that investigated the relationship between weight loss and blood levels of two major angiogenic factors.
The McTiernan group previously conducted a 12-month randomized controlled trial in which 439 healthy postmenopausal overweight or obese women were randomized to either a control group or one of three intervention arms: reduced calorie diet with the goal of 10% weight loss, exercise with the goal of 45 minutes of moderate to vigorous exercise 5 days/week, or both diet and exercise (the Nutrition and Exercise in Women (NEW) study). In an ancillary study, 3 important angiogenic factors – VEGF, PEDF, and PAI-1 – were measured from stored blood at baseline and 12 months (1). Dr. Catherine Duggan, a principal staff scientist in the McTiernan group, described some of the major results from that parent study, “after 1 year, levels of VEGF, PAI-1, and PEDF were statistically significantly reduced among participants who lost weight.”
While the study results after 12 months of intervention were encouraging, it remained unknown whether changes in the angiogenic factors would be sustained long-term. This question led to an additional study, “In an ancillary study (NOW), we followed up participants 30 months post-randomization – i.e., 18 months after the study ended, to see if weight loss was maintained in the intervention arms and if so, did the effects on angiogenesis markers persist,” explained Duggan. The follow-up phase of the study included 156 women from the NEW study, who agreed to return to the clinic and provide a blood sample, and complete questionnaires and anthropometric measurements. Circulating levels of both VEGF and PEDF were measured. The authors found that at 30 months post-randomization, the diet + exercise group had maintained the most weight loss, followed by the diet only and then the control and exercise groups. The authors also found that all three intervention groups had significantly reduced levels of circulating VEGF, but not PEDF, from baseline to 30 months as compared to the control group.
The earlier study suggested that change in body weight may have explained most of the changes in blood levels of the angiogenic factors. This led the authors to assess long-term changes in VEGF and PEDF by amount of weight loss from baseline to 30 months post-randomization. The participants were categorized into one of four weight loss groups, £ 0%, 0 – 5%, 5 – 10%, or ³ 10%. Only the group that had lost ³ 10% body weight since baseline had significantly reduced VEGF levels compared to the control group (see figure). In contrast, PEDF levels were significantly lower in all three weight groups that had lost weight, although the greatest effect was again observed in the ³ 10% weight loss group. These results demonstrate that sustained weight loss exerts long-term effects on circulating angiogenic factors. Changes in the levels of these angiogenic factors may impart beneficial effects in protection against cancer development, but additional follow-up studies are necessary to confirm this link.
Also contributing to this project from the Fred Hutch were Drs. Jean de Dieu Tapsoba and Ching-Yun Wang.
Duggan C, Tapsoba JdD, Wang C-Y, Foster-Schubert KE, McTiernan A. 2017. Long-term Effects of Weight Loss & Exercise on Biomarkers Associated with Angiogenesis. Cancer Epidemiol Biomarkers Prev. 26(12):1-7.
1. Duggan C, Tapsoba JdD, Wang C-Y, McTiernan A. 2016. Dietary weight loss and exercise effects on serum biomarkers of angiogenesis in overweight postmenopausal women: a randomized controlled trial. Cancer Res. 76(14):4226-4235.
Funding for this study was provided by the National Cancer Institute and the Breast Cancer Research Foundation.