A new study has reported a mechanism of action by which exercise may improve prognosis among those with breast cancer. The study was designed to investigate the effects of physical activity on DNA methylation, gene expression, and breast cancer survival. DNA methylation, which is associated with DNA replication, is involved in a number of processes, among them regulation of tumor suppressor genes. Altered DNA methylation may suppress transcription and, subsequently, gene expression.
To conduct the study, blood samples, which had been collected from 12 breast cancer patients who participated in a previous clinical trial of exercise, were examined for exercise-related changes in DNA methylation using a methylation microarray. For comparison, tumor samples of 348 breast cancer patients were analyzed to determine gene expression and methylation.
Blood drawn after six months of moderate-intensity aerobic exercise showed significant changes in DNA methylation in 43 of 14,495 genes tested. Based on this list of genes, the authors analyzed gene expression in breast tumors in association with overall survival. Three genes were found whose methylation was reduced after exercise and that were favorably associated with overall survival. One of the three is generally considered a tumor suppressor gene and is known to be activated mainly in stem cells. Additional analyses of the comparison group of breast cancer patients found that high expression of this gene was associated with low grade and hormone receptor positive tumors (which are the least aggressive), as well as low risk of recurrence and breast cancer-specific death. The authors conclude that increasing physical activity after a breast cancer diagnosis may affect regulation of tumor suppressor genes in ways that have favorable influence on survival outcomes.