Physical Activity, Global DNA Methylation, and Breast Cancer Risk: A Systematic Literature Review and Meta-analysis

Abstract

The extent to which physical activity reduces breast cancer risk through changes in global DNA methylation is unknown. We systematically identified studies that investigated the association between: (i) physical activity and global DNA methylation; or (ii) global DNA methylation and breast cancer risk. Associations were quantified using random-effects models. Heterogeneity was investigated through subgroup analyses and the -test and statistics. Twenty-four studies were reviewed. We observed a trend between higher levels of physical activity and higher levels of global DNA methylation [pooled standardized mean difference = 0.19; 95% confidence interval (CI), -0.03-0.40; = 0.09] which, in turn, had a suggestive association with a reduced breast cancer risk (pooled relative risk = 0.70; 95% CI, 0.49-1.02; = 0.06). In subgroup analyses, a positive association between physical activity and global DNA methylation was observed among studies assessing physical activity over long periods of time ( = 0.02). Similarly, the association between global DNA methylation and breast cancer was statistically significant for prospective cohort studies ( = 0.007). Despite the heterogeneous evidence base, the literature suggests that physical activity reduces the risk of breast cancer through increased global DNA methylation. This study is the first to systematically overview the complete biologic pathway between physical activity, global DNA methylation, and breast cancer.

Rowing Training in Breast Cancer Survivors: A Longitudinal Study of Physical Fitness

“…Physical activity decreases the duration and intensity of fatigue [ 8 , 9 ], reduces anxiety and depression [ 10 ], increases muscle mass and strength, decreases disability in the upper extremities [ 11 ] and improves quality of life [ 12 , 13 ], as well as restoring and even improving functionality and well-being in women who have overcome breast cancer [ 14 ]. Several meta-analyses and reviews affirm that physical activity also contributes to reducing the risk of breast cancer recurrence [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], while others have obtained neutral results, implying that physical activity does not cause any changes [ 29 , 30 , 31 ].…”

“…Consequently, this study followed the recommendations of the American College of Sports Medicine (ACSM), which state that cancer survivors should perform 150 min of moderate aerobic activity or 75 min of vigorous aerobic activity per week and resistance training two days per week [ 32 ]. Physical exercise plays an important role in improving quality of life [ 11 ] and preventing or delaying the onset of other diseases in cancer survivors [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ] by improving aerobic capacity and muscle strength [ 11 ] and reducing fatigue [ 8 ], all of which are key elements in recovery from this disease and its sequelae [ 32 ].…”

Epigenome-wide DNA methylation and risk of breast cancer: a systematic review

“…A growing body of evidence suggests that well known breast cancer risk factors are associated with global DNA hypomethylation and increased epigenetic age [ 40 ], including lifestyle and dietary factors [ 41 , 42 ], body mass index [ 43 ], physical inactivity [ 44 ], and hormone exposure [ 45 ]. Furthermore, global DNA hypomethylation has been observed in cancers [ 46 ], including breast carcinomas, indicating that DNA methylation mediates gene-environment interactions.…”

Dietary fat and obesity as modulators of breast cancer risk: Focus on DNA methylation

“…Changes in body fat percentage were positively associated with LINE‐1 methylation values. In contrast to obesity, increased exercise was associated with a decreased risk of BC, and meta‐analyses have suggested that this may be due to a positive association between global CpG methylation and physical activity (Boyne et al, )…”

“…Changes in body fat percentage were positively associated with LINE-1 methylation values. In contrast to obesity, increased exercise was associated with a decreased risk of BC, and meta-analyses have suggested that this may be due to a positive association between global CpG methylation and physical activity (Boyne et al, 2018) A methylation study of RARβ, E-cadherin 1 (ECAD) and P16 in (n = 803) breast tumour blocks from the Western New York Exposure and BC Study found that a greater WHR was associated with an increased probability (OR = 1.85) of hypermethylation of one or more of these genes (Tao et al, 2011). An analysis of non-malignant breast tissue from healthy women (n = 120) who had undergone cosmetic mammoplasty reported hypermethylation of ESR1 in obese women (BMI of ≥30 kgÁm −2 ) compared to both overweight (BMI of~25-29 kgÁm −2 ) and normal weight (BMI of <25 kgÁm −2 ; Daraei et al, 2017).…”