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Aerobic exercise and DNA methylation in postmenopausal women: An ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial.

ABSTRACT: Physical activity is associated with a lower risk of breast, colon, and endometrial cancer. Epigenetic mechanisms such as changes in DNA methylation may help to explain these protective effects. We assessed the impact of a one year aerobic exercise intervention on DNA methylation biomarkers believed to play a role in carcinogenesis. The Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial was a two-armed randomized controlled trial in 320 healthy, inactive, postmenopausal women with no history of cancer. In an ancillary analysis, frozen blood samples (n = 256) were reassessed for levels of DNA methylation within LINE-1 and Alu repeats as well as within the promoter regions of APC, BRCA1, RASSF1, and hTERT genes. Differences between the exercise and control arm at 12-months, after adjusting for baseline values, were estimated within an intent-to-treat and per-protocol analysis using linear regression. No significant differences in DNA methylation between the exercise and control arms were observed. In an exploratory analysis, we found that the prospective change in estimated VO2max was negatively associated with RASSF1 methylation in a dose-response manner (p-trend = 0.04). A year-long aerobic exercise intervention does not affect LINE-1, Alu, APC, BRCA1, RASSF1, or hTERT methylation in healthy, inactive, postmenopausal women. Changes in DNA methylation within these genomic regions may not mediate the association between physical activity and cancer in healthy postmenopausal women. Additional research is needed to validate our findings with RASSF1 methylation. TRIAL REGISTRATION:ClinicalTrials.gov NCT00522262.

SUBMITTER: Boyne DJ

PROVIDER: S-EPMC6023230 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Aerobic exercise and DNA methylation in postmenopausal women: An ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial.

Boyne Devon J DJ King Will D WD Brenner Darren R DR McIntyre John B JB Courneya Kerry S KS Friedenreich Christine M CM

PloS one 20180628 6

Physical activity is associated with a lower risk of breast, colon, and endometrial cancer. Epigenetic mechanisms such as changes in DNA methylation may help to explain these protective effects. We assessed the impact of a one year aerobic exercise intervention on DNA methylation biomarkers believed to play a role in carcinogenesis. The Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial was a two-armed randomized controlled trial in 320 healthy, inactive, postmenopausal women w ...[more]

PMID: 29953441

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Project description:BackgroundPhysical activity has emerged as an important lifestyle factor for primary prevention of numerous diseases, including postmenopausal breast cancer. No study to date has assessed the acute and long-term effects of year-long aerobic exercise programs differing in prescribed exercise volume on physical activity and sedentary time in postmenopausal women. Therefore, we aimed to examine the effects of two moderate-vigorous intensity exercise doses on total, light and moderate-vigorous intensity physical activity times, and sedentary time in postmenopausal women during the year-long intervention and one year later.MethodsThe Breast Cancer and Exercise Trial in Alberta (BETA) was a two-center, two-arm, 12-month randomized controlled trial that included 400 previously inactive postmenopausal women randomized to either 150 (MODERATE) or 300 (HIGH) minutes/week of aerobic exercise. Physical activity and sedentary time were assessed at baseline, 6- (intervention mid-point), 12- (prior to end of intervention) and 24-months (follow-up) with waist-mounted accelerometers (Actigraph GTX3®). Self-reported activity and sedentary time at baseline, 12- and 24-months was also assessed (Past Year Total Physical Activity Questionnaire and SIT-Q). Intention-to-treat analyses were conducted using linear mixed models and adjusted for baseline variables.ResultsBoth physical activity interventions led to increases in objective and subjective measures of total and moderate-vigorous intensity/recreational physical activity time, coupled with decreases in sedentary time, at 6- and 12-months compared to baseline. Additionally, greater increases in accelerometry-derived total physical activity time at 6- and 12-months, and self-reported recreational activity time at 12-months, compared to baseline were noted in the HIGH versus MODERATE groups. Decreases in total, light and moderate-vigorous intensity physical activity time, and an increase in sedentary time, in both groups were noted at 24-months compared to 12-months. A decrease in light intensity physical activity time in both groups at 24-months compared to baseline was also noted.ConclusionThese findings have important health implications, suggesting that total physical activity time can be increased with greater volumes of prescribed exercise, but that additional support and resources could be used to promote the maintenance of these high levels of aerobic exercise participation following study completion.Trial registrationclinicaltrials.gov identifier: NCT01435005 (BETA Trial). Registred September 15th 2011 (retrospectively registered).

Project description:Despite the clear health benefits of exercise, exercised-induced weight loss is often less than expected. The term 'exercise energy compensation' is used to define the amount of weight loss below what is expected for the amount of exercise energy expenditure. We examined the dose-response effects of exercise volume on energy compensation in postmenopausal women.Data from Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were combined for the present analysis. The ALPHA and BETA trials were two-centred, two-armed, 12-month randomized controlled trials. The ALPHA trial included 160 participants randomized to 225 min per week of aerobic exercise, and the BETA trial randomized 200 participants to each 150 and 300 min per week of aerobic exercise. All participants were aged 50-74 years, moderately inactive (<90 min per week of exercise), had no previous cancer diagnosis and a body mass index between 22 and 40 kg m-2. Energy compensation was based on changes in body composition (dual-energy X-ray absorptiometry scan) and estimated exercise energy expenditure from completed exercise volume. Associations between Δenergy intake, ΔVO2peak and Δphysical activity time with energy compensation were assessed.No differences in energy compensation were noted between interventions. However, there were large inter-individual differences in energy compensation between participants; 9.4% experienced body composition changes that were greater than expected based on exercise energy expenditure, 64% experienced some degree of energy compensation and 26.6% experienced weight gain based on exercise energy expenditure. Increases in VO2peak were associated with reductions in energy compensation (β=-3.44 ml kg-1 min-1, 95% confidence interval for β=-4.71 to -2.17 ml kg-1 min-1; P=0.0001).Large inter-individual differences in energy compensation were noted, despite no differences between activity doses. In addition, increases in VO2peak were associated with lower energy compensation. Future studies are needed to identify behavioral and metabolic factors that may contribute to this large inter-individual variability in energy compensation.

Dataset Information

Aerobic exercise and DNA methylation in postmenopausal women: An ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial.

Publications

Aerobic exercise and DNA methylation in postmenopausal women: An ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial.

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