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DOSE-DEPENDENT EFFECT OF AEROBIC EXERCISE ON THE CONCENTRATION OF INFLAMMATORY BIOMARKERS IN A POPULATION OF WOMEN AT HIGH RISK FOR BREAST CANCER
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Haley, Jeremy Scott
Public Health Sciences
Master of Science
Date of Defense:
April 02, 2018
Kathleen M Sturgeon, Thesis Advisor
Kathryn Schmitz, Committee Member
Kristen H Kjerulff, Committee Member
Women who are carriers of mutations in BRCA1 and BRCA2 are at an increased risk of developing breast cancer. In addition to BRCA, there are other mutations that also increase one’s risk of developing breast cancer. BRCA and other BC-associated gene mutations have been shown to be integral components of the pathways that repair damaged DNA and arrest the cell cycle. DNA damage occurs naturally by multiple mechanisms including oxidative stress. Higher levels of oxidative stress can be caused by inflammation. Therefore, a chronic inflammatory state can lead to higher oxidative stress, which will cause more DNA damage and a higher mutational load that place carriers of BC-associated gene mutations at a higher cancer risk. Women at known high risk for breast cancer are often highly motivated to reduce risk. In contrast with costly and invasive risk reduction strategies such as mastectomy, lifestyle changes such as exercise may help decrease breast cancer risk as well as risk of other life threatening diseases via a change in levels of inflammation. This study assessed a panel of inflammatory biomarkers both before and after an aerobic exercise intervention over the course of five menstrual cycles in high risk, premenopausal women who participated in the Women In Steady Exercise Research (WISER) Sister study. Participants were randomly assigned to either a control, low-dose, or high-dose exercise group. Those randomized to exercise were asked to complete 150 (low dose) or 300 minutes per week (high dose) of aerobic exercise. The biomarker panel included CCL2, IL10, IL12 and TNFα. Changes in the levels of these biomarkers were compared both within and between treatment groups. Exercise dose-dependent changes in levels of CCL2, IL10, IL12 and TNFα were also analyzed across groups via testing for significant linear trends. We found a significant dose-dependent increase in levels of the pro-inflammatory biomarkers CCL2 (Ptrend=0.05), IL12 (Ptrend<0.001) and TNFα (Ptrend<0.001). The exercise intervention significantly increased fitness capacity (Ptrend<0.001) and energy expenditure (Ptrend<0.001). The intervention also significantly decreased total mass (Ptrend = 0.03), total fat mass (Ptrend =0.001) and percent body fat (Ptrend<0.001). Changes in total fat mass and percent body fat were significantly associated with a decrease in IL10 levels for the control group only. No other biomarker was significantly associated with a change in total mass, total fat mass or percent body fat. Overall, participants in the study experienced improved body composition and energetic measures but increased levels of inflammation. The majority of studies agree that increased physical activity and lower levels of inflammation can reduce a women’s risk of developing BC. Additionally, most studies have shown that physical activity is capable of improving levels of inflammation. However, to our knowledge there has not been a study assessing how a dosed aerobic exercise intervention can affect levels of inflammation in a population of women at increased risk of BC. The number of women at high risk of developing BC will continue to grow as new BC-associated genes are discovered. Due to the increased level of inflammation following exercise reported here, future studies must focus on whether aerobic exercise is able to benefit these high risk women.
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