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Breaking Down AGEs

Image of a green spork that is holding a variety of pills.

Insight into how lifestyle drives ER-positive breast cancer

By Caroline Wallace

The underlying biological connection of poor diet and lack of exercise to cancer development is not well understood. Insight into advanced glycation end products (AGEs) offers a biological link between certain lifestyle behaviors and cancer risk. AGE accumulation is the natural and unavoidable result of the breakdown of sugars and fats. AGE levels, however, are increased by the over-consumption of foods high in sugar and fat.

High AGE levels could prevent patients with estrogen receptor (ER)-positive breast cancer from responding to tamoxifen therapy, suggest preclinical findings reported by MUSC researchers in a recent issue of Breast Cancer Research and Treatment. The research team was led by College of Medicine Assistant Professor David P. Turner, Ph.D., Professor Marvella E. Ford, Ph.D., and Gayenell Magwood, R.N., Ph.D., F.A.A.N. Ford is also the associate director of population sciences and cancer disparities at Hollings Cancer Center.

“By showing that AGEs in the diet may impact how well breast cancer patients respond to therapy, we can make breast cancer patients aware of their existence,” says Turner. “And we can design lifestyle interventions aimed at reducing AGE intake.”

AGEs cause an imbalance between molecules called free radicals and antioxidants. This imbalance leads to chronic inflammation that can promote the development of a variety of chronic diseases such as diabetes, Alzheimer’s Disease, cardiovascular disease, arthritis and cancer. However, AGEs have not been studied in-depth in the context of cancer.

High AGE levels lead to continual activation of pro-cancer pathways. A central molecule turned on by the pro-cancer pathways is important in the context of ER-positive and -negative breast cancers. The MUSC team found that AGEs actually increase the function (through phosphorylation) of estrogen receptor alpha in breast cancer cell lines. Adding tamoxifen to the cancer cells prevented their growth. However, adding AGEs caused them to grow once again. This indicates that patients with high AGEs may be less likely to respond to tamoxifen treatment.

In fact, a defined lifestyle intervention of exercise and dietary counseling lowered systemic levels of AGEs in overweight women with non-metastatic, ER-positive breast cancer.

Expanding the published study to determine the effects of the intervention on a larger scale will shed light on how lifestyle interventions can beneficially affect cancer treatments by reducing AGE levels.