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

Devon J Boyne,Kerry S Courneya,Christine M Friedenreich,Darren R Brenner,Will D King,John B Mcintyre,Hiromu Suzuki

doi:10.1371/journal.pone.0198641

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.

Highlights

Regular physical activity has been shown to protect against a multitude of cancers in a wide variety of study populations and settings
It was recently estimated that roughly 7% of colorectal and breast cancer cases worldwide were attributable to physical inactivity in 2013, representing a total healthcare cost of $5.2 billion for these two cancer sites alone [4]
We investigated the association between the amount of physical activity, weight loss, and change in aerobic fitness that occurred during the intervention and differences in DNA methylation at 12-months

Summary

Introduction

Regular physical activity has been shown to protect against a multitude of cancers in a wide variety of study populations and settings. It is well established that being more physically active lowers the risk of colorectal, breast, and endometrial cancer [1, 2]. A recent pooled analysis of 1.44 million individuals suggested that the protective effects of physical activity extend to head and neck, esophageal, lung, kidney, blood, and bladder cancers independent of body mass index [3]. The burden of cancer attributable to physical inactivity is considerable. It was recently estimated that roughly 7% of colorectal and breast cancer cases worldwide were attributable to physical inactivity in 2013, representing a total healthcare cost of $5.2 billion for these two cancer sites alone [4]

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