Role of Physical Activity in Modulating Breast Cancer Risk as Defined byAPCandRASSF1APromoter Hypermethylation in Nonmalignant Breast Tissue

Abstract

Physical activity reduces breast cancer risk. Promoter hypermethylation of the tumor suppressor genes APC and RASSF1A, which is potentially reversible, is associated with breast cancer risk. We conducted a cross-sectional study in 45 women without breast cancer to determine the association of physical activity with promoter hypermethylation of APC and RASSF1A in breast tissue. We used quantitative methylation-specific PCR to test the methylation status of APC and RASSF1A, and questionnaires to assess study covariates and physical activity (measured in metabolic equivalent hours per week). In univariate analyses, the study covariate, benign breast biopsy number, was positively associated with promoter hypermethylation of APC (P = 0.01) but not RASSF1A. Mulitvariate logistic regression indicated that, although not significant, physical activities for a lifetime [odds ratio (OR), 0.57; 95% confidence interval (95% CI), 0.22-1.45; P = 0.24], previous 5 years (OR, 0.62; 95% CI, 0.34-1.12; P = 0.11), and previous year (OR, 0.72; 95% CI, 0.43-1.22; P = 0.22) were inversely related to promoter hypermethylation of APC but not RASSF1A for all physical activity measures. Univariate logistic regression indicated that physical activities for a lifetime, previous 5 years, and previous year were inversely associated with benign breast biopsy number, and these results were approaching significance for lifetime physical activity (OR, 0.41; 95% CI, 0.16-1.01; P = 0.05) and significant for physical activity in the previous 5 years (OR, 0.57; 95% CI, 0.34-0.94; P = 0.03). The study provides indirect evidence supporting the hypothesis that physical activity is inversely associated with promoter hypermethylation of tumor suppressor genes, such as APC, in nonmalignant breast tissue. (Cancer Epidemiol Biomarkers Prev 2007;16(2):192 -6)

Adiposity and Age are Statistically Related to EnhancedRASSF1ATumor Suppressor Gene Promoter Methylation in Normal Autopsy Kidney Tissue

“…Accordingly, it has been hypothesized that a lack of physical activity is associated with increased methylation of tumor suppressor genes in normal breast tissue (38). Some recent findings could provide a biological explanation for the statistical relationship between BMI and increased promoter methylation in normal kidney tissue.…”

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…For instance, physical activities for at least one year are inversely related to promoter hypermethylation of the tumor suppressor gene APC in breast cancer (Coyle et al, 2007). These studies in cancer suggest that exercise induces epigenetic modifications that could be behind its health beneficial effects.…”

Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1

“…Few studies have investigated the relationship between physical activity and DNA methylation in cancer patients. Two small observational studies found possible associations between physical activity and DNA methylation of the tumor suppressor genes APC and CACNA2D3 [13,14]. Our study is the first to demonstrate the effect of exercise on DNA methylation in a randomized clinical trial.…”

“…As part of the regulation, DNA methylation is involved in tumor progression. A small study of breast specimens found physically active women to have low methylation in the APC gene [13]. As a tumor suppressor gene, an active APC is considered to be beneficial.…”