Diet, exercise decrease biomarkers associated with cancer development

Obese and overweight postmenopausal women who lost weight through diet and exercise demonstrated reductions in serum biomarkers of angiogenesis, according to the results of a randomized trial.

These biomarkers included VEGF, pigment epithelium-derived factor (PEDF) and plasminogen activator inhibitor-1 (PAI-1).

Catherine Duggan

“We know that being overweight and having a sedentary lifestyle is associated with an increase in risk for developing certain types of cancer,” Catherine Duggan, PhD, principle staff scientist in the public health sciences division at Fred Hutchinson Cancer Research Center of Seattle Cancer Care Alliance, said in a press release. “We wanted to investigate how levels of some biomarkers associated with angiogenesis were altered when overweight, sedentary, postmenopausal women enrolled in a research study lost weight and/or became physically active over the course of a year.”

Duggan and colleagues investigated changes from baseline to 12 months in three serum protein markers that have been studied extensively in obesity and have been implicated in tumorigenesis: VEGF, a key regulator of angiogenesis; PAI-1, a serine protease inhibitor; and PEDF, an adipokine serine protease inhibitor.

Researchers randomly assigned 439 postmenopausal women (84.9% non-Hispanic white; mean age, 57.9 years; mean BMI, 30.9) to one of four arms:

diet arm, in which women restricted their caloric intake to 2,000 kcal per day, less than 30% of which could be from fat calories (n = 118);

aerobic exercise arm, in which women performed 45 minutes of moderate to vigorous exercise 5 days per week (n = 117);

diet plus exercise arm (n = 117); or

control arm (n = 87).

After 12 months, participants had a physical examination and provided a blood sample. The mean weight change was –0.8% in the control arm. Weight loss was significantly greater among women in the exercise arm (–2.4%; P = .03), diet arm (–8.5% P < .001) and diet-plus-exercise arm (–10.8%; P < .001). The percent body fat reduction was significantly greater in all three intervention arms (P < .001).

Overall, the control group experienced a 0.18% increase in PEDF, a –1.21% decrease in VEGF and a 3.48% increase in PAI-1.

Analyses adjusted for baseline BMI, age and race/ethnicity showed that PEDF and VEGF significantly reduced among women in the diet arm (PEDF, –9.2%; P < .0001; VEFG, –8.25%; P = .0005) and diet-plus-exercise arm (PEDF, –9.9%; VEGF, –9.98%; P < .0001) compared with controls. PAI-1 only significantly decreased among women in the diet-plus-exercise arm (–19.3%; P < .0001).

These differences did not occur in the exercise-alone arm.

Further, an analysis based on percentage of weight lost suggested that increasing weight loss was significantly associated with linear reductions in PAI-1 (diet, P = .0003; diet plus exercise, P < .0001), PDEF and VEGF (P < .0001 for both).

Researchers acknowledged that the homogenous nature of the cohort may have limited findings.

“Our study shows that weight loss is a safe and effective method of improving the angiogenic profile in healthy individuals,” Duggan said. “Exercise is important for helping prevent weight gain, and to maintain weight loss, but does not cause a large amount of weight loss on its own. Making lifestyle changes — in this case simple changes to the diet to reduce weight — can lower the risk factors for cancer.” – by Nick Andrews

Disclos ure: The researchers report no relevant financial disclosures.

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Source:

Duggan C, et al. Cancer Res. 2016;doi:10.1158/0008-5472.CAN-16-0399.