Influence of Exercise on Inflammation in Cancer

Direct Effect or Innocent Bystander?

E. Angela Murphy; Reilly T. Enos; Kandy T. Velázquez


Exerc Sport Sci Rev. 2015;43(3):134-142. 

In This Article

Abstract and Introduction


We propose the hypothesis that the benefits of exercise on inflammation in cancer are a result of a direct effect on inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein 1, that are critical for cancer growth as well as a bystander effect of the established relationship between exercise and cancer.


According to the World Health Organization, physical inactivity is the fourth leading risk factor for mortality globally; it is responsible for 6% of all deaths worldwide. Specifically, physical inactivity has emerged as a leading behavioral risk factor for certain cancers. In fact, the American Cancer Society speculates that the increase in cancer incidence among the younger population is, at least in part, caused by a sedentary lifestyle as rates of cancer incidence in individuals younger than 50 yr are on the rise. Conversely, physical activity has been linked to a reduced risk for various cancers; epidemiological studies indicate an inverse association between physical activity and cancer risk, and controlled experiments in rodent models substantiate these claims. For example, our research supports an exercise-induced decrease in tumorigenesis in mouse models of breast cancer and colon cancer.[25,28,34] However, the mechanisms responsible for this relationship have not yet been established.

The mechanisms for a beneficial effect of physical activity on cancer risk are likely to be complex and multifaceted; several interrelated mechanisms including adiposity, energy balance, adipokines, insulin, estrogen, and immune function have all been investigated as possible contributing factors. Recently, it has been suggested that a physical activity–induced reduction in inflammation may play a significant role. Inflammation has been linked to every event involved in the development and progression of cancer, and physical activity has been reported to reduce inflammatory processes. Research from our laboratory supports this association as we have seen a decrease in inflammatory mediators with physical activity in rodent models of cancer that has been linked to decreased tumorigenesis.[25,28] However, whether the benefits of physical activity on inflammation in cancer are a result of a direct effect on inflammatory pathways that are critical for cancer growth or merely just a bystander effect of the established relationship between physical activity and cancer has not yet been elucidated firmly.

The purpose of this article is to propose the hypothesis that exercise has both a direct and an indirect effect on inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein 1 (MCP-1)) that leads to decreased tumorigenesis. Although beneficial effects of physical activity have been observed for most, if not all, malignancies, the majority of this evidence to date has been centered on colon cancer and breast cancer. This is not surprising given the prevalence of these cancers and their propensity to be altered by lifestyle factors. Thus, this article will focus largely on the available evidence for the benefits of physical activity on breast cancer and colon cancer.