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Long-term Effects of Moderate versus High Durations of Aerobic Exercise on Biomarkers of Breast Cancer Risk: Follow-up to a Randomized Controlled Trial.
Friedenreich, CM, Wang, Q, Yasui, Y, Stanczyk, FZ, Duha, A, Brenner, DR, Courneya, KS
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2019;(10):1725-1734
Abstract
BACKGROUND The optimal lifestyle for breast cancer prevention over the long term is unclear. We aimed to determine whether or not the amount of exercise prescribed in a year-long exercise intervention influences breast cancer biomarker levels 1 year later. METHODS We conducted a 24-month follow-up study (2012-2014) to the Breast Cancer and Exercise Trial in Alberta (BETA), a 12-month, two-armed (1:1), two-center randomized controlled trial of exercise in 400 cancer-free, postmenopausal women. The exercise prescription was moderate-vigorous aerobic exercise, 5 days/week (3 days/week supervised) for 30 minutes/session (MODERATE) or 60 minutes/session (HIGH). Participants were asked not to change their usual diet. We used linear mixed models to compare biomarker concentrations (C-reactive protein, insulin, glucose, HOMA-IR, estrone, sex hormone binding globulin, total estradiol, and free estradiol) over time (0, 12, and 24 months) by group (MODERATE, HIGH), using group-time interactions. RESULTS After 12 months of no intervention, 24-month fasting blood samples were available for 84.0% and 82.5% of MODERATE and HIGH groups, respectively (n = 333/400). We found no evidence that 0 to 24- or 12 to 24-month biomarker changes differed significantly between randomized groups (HIGH:MODERATE ratio of mean biomarker change ranged from 0.97 to 1.06, P values >0.05 for all). We found more favorable biomarker profiles among participants who experienced greater than the median fat loss during the trial. CONCLUSIONS Prescribing aerobic exercise for 300 versus 150 minutes/week for 12 months to inactive, postmenopausal women had no effects on longer-term biomarkers. IMPACT Exercise may lead to larger improvements in breast cancer biomarkers after intervention among women who also experience fat loss with exercise.
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Dietary modifications, weight loss, and changes in metabolic markers affect global DNA methylation in Hispanic, African American, and Afro-Caribbean breast cancer survivors.
Delgado-Cruzata, L, Zhang, W, McDonald, JA, Tsai, WY, Valdovinos, C, Falci, L, Wang, Q, Crew, KD, Santella, RM, Hershman, DL, et al
The Journal of nutrition. 2015;(4):783-90
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Abstract
BACKGROUND Lower levels of global DNA methylation in tissue and blood have been associated with increased cancer risk. Conversely, cross-sectional analyses of healthier lifestyle patterns have been associated with higher levels of global DNA methylation. OBJECTIVE In this trial, we explored the associations between changes in lifestyle modifications (diet, weight loss), metabolic markers, and global epigenetic biomarkers in white blood cells. METHODS Study participants were Hispanic, African American, and Afro-Caribbean overweight and sedentary female breast cancer survivors (n = 24) who participated in a larger randomized, crossover, pilot study of a 6-mo weight loss intervention and who had available blood specimens. Anthropometric measures, a food-frequency questionnaire, and peripheral blood were collected at baseline, 6 mo, and 12 mo. Plasma samples were analyzed for metabolic markers (insulin, glucose). We measured DNA methylation of long interspersed nucleotide element 1 (LINE-1) and satellite 2 by pyrosequencing and MethyLight, respectively, and global DNA methylation by the luminometric methylation assay (LUMA). RESULTS DNA methylation of LINE-1 was statistically significantly elevated at 6 mo [75.5% vs. 78.5% (P < 0.0001)] and 12 mo [75.5% vs. 77.7% (P < 0.0001)], compared to baseline. Over a 12-mo period, changes in percentage body fat and plasma glucose concentrations were positively associated with LINE-1 DNA methylation (β = 0.19, P = 0.001) and LUMA DNA methylation levels (β = 0.24, P = 0.02), respectively. Similarly, 12-mo changes in dietary measures such as vegetable (β = 0.009, P = 0.048), protein (β = 0.04, P = 0.001), and total caloric (β = 0.05, P = 0.01) intake were positively associated with changes in LUMA DNA methylation, as was intake of fruit positively associated with changes in LINE-1 DNA methylation (β = 0.004, P = 0.02). CONCLUSIONS Our hypothesis-generating results suggest that lifestyle modifications may be associated with changes in global DNA methylation detectable at 6 and 12 mo. These biomarkers may be useful intermediate biomarkers to use in future intervention trials. This trial was registered at clinicaltrials.gov as NCT00811824.