Study links elevated levels of advanced glycation end-products (AGEs) with breast cancer risk

Hollings Cancer Center researchers at the Medical University of South Carolina (MUSC) and colleagues assessed the connection between dietary advanced glycation end products (AGEs) and breast cancer risk in a study first published online March 2020 in Cancer Prevention Research.

It supports an increasingly evident link between high levels of AGEs in the body and cancer risk, said principal investigator David Turner, Ph.D., who worked with colleagues Susan Steck, Ph.D., with the University of South Carolina, and Lindsay Peterson, M.D., with Washington University School of Medicine.

The study was part of a larger decade-long prostate, lung, colorectal and ovarian cancer screening trial (PLCO) designed and sponsored by the National Cancer Institute. It included over 78,000 women between the ages of 55 and 74 years who were cancer free at the start of the study. The women completed a food frequency questionnaire at the beginning and again at five years into the study. After an average of 11 ½ years, 1,592 of the women were diagnosed with breast cancer. When the intake of high-AGE food was assessed, based on the questionnaires, increased AGE intake via the diet was associated with an increased risk of in situ and hormone receptor positive breast cancers.

Advanced glycation end products are proteins and lipids (fats) that go through a chemical alteration called glycation when they are exposed to sugars. This process occurs naturally in the body. However, processed foods and foods cooked at high temperatures are extremely high in AGEs, which can lead to a dangerous overabundance in the body.

Turner said AGEs are involved in nearly every chronic disease, in some way. “The study of AGEs in cancer is just starting to get traction. The presence of AGEs has been known for at least 100 years, but the research has been challenging. In order to determine how they work, their mechanism of action, researchers first have to determine a role in various diseases.”

Turner said this study is important because it adds to the evidence between high levels of AGEs in the body and cancer risk. Turner and his collaborators are promoting the connection between AGEs and lifestyle choices to help the public make better food choices.

This will become an even more popular area of study as researchers employ new tools to help study AGEs. “A novel device, the AGE reader, is about to change how we look at AGEs in the clinic,” Turner said. The AGE reader, made by Diagnoptics, is an easy to use noninvasive device where someone rests their forearm for just 12 seconds. It uses light at certain wavelengths to excite AGE autofluorescence in the human skin tissue.

“This machine actually measures glow from some of the AGEs. The more AGEs that are in the skin, the higher the glow,” explained Turner.

While the AGE reader has been used to show strong correlations between AGE levels and Type 2 diabetes, cardiovascular disease and even mortality, Turner is using a cancer center support grant to validate further the AGE reader for use in cancer patients. He and his colleagues plan to investigate whether pigmentation in the skin skews the reading and use the reader as part of a growing community outreach program.

Since a link between AGEs and breast cancer has been shown, the ultimate goal is to test all Hollings Cancer Center patients who are interested at each visit, Turner said. This will provide a huge amount of data about the link between AGEs and a wide variety of cancers. Turner and his collaborators expect that future multicenter grants will come out of this project.

While the connection between high AGE levels and cancer risk might be disconcerting, research is also being done to determine if there is a way to reverse the detrimental effects of AGEs.

Bradley Krisanits, a Ph.D. student in Turner’s lab, said that preliminarily, they have seen that physical activity reduces the amount of AGEs in the circulation.

“In our prostate cancer models, we see that physical activity counteracts prostate cancer progression in mice fed a high-AGE diet. This may be occurring due to a reduction in AGEs and changes in the immune system that we need to study more.”

Turner hopes that by educating people about AGEs, they can make informed lifestyle decisions and lower their risks for chronic diseases. The top three things that a person can do is learn what AGEs are, avoid processed foods and think about how you cook your food in order to make changes to avoid the highest AGE-inducing cooking methods such as frying, grilling and broiling.

“AGEs build up in a cumulative way. Fats, sugars, everything that is bad for you leads to the accumulation of AGEs. One of our goals at Hollings is to reach out to the community to encourage the public to make healthier choices. Just making small changes in your diet can have a big effect.”

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About the Medical University of South Carolina

Founded in 1824 in Charleston, MUSC is the oldest medical school in the South as well as the state’s only integrated academic health sciences center with a unique charge to serve the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and 800 residents in six colleges: Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy. The state’s leader in obtaining biomedical research funds, in fiscal year 2019, MUSC set a new high, bringing in more than $284 million. For information on academic programs, visit http://musc.edu.

As the clinical health system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest quality patient care available while training generations of competent, compassionate health care providers to serve the people of South Carolina and beyond. Comprising some 1,600 beds, more than 100 outreach sites, the MUSC College of Medicine, the physicians’ practice plan and nearly 275 telehealth locations, MUSC Health owns and operates eight hospitals situated in Charleston, Chester, Florence, Lancaster and Marion counties. In 2019, for the fifth consecutive year, U.S. News & World Report named MUSC Health the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit http://muschealth.org.

MUSC and its affiliates have collective annual budgets of $3.2 billion. The more than 17,000 MUSC team members include world-class faculty, physicians, specialty providers and scientists who deliver groundbreaking education, research, technology and patient care.

About Hollings Cancer Center

The Hollings Cancer Center at the Medical University of South Carolina is a National Cancer Institute-designated cancer center and the largest academic-based cancer research program in South Carolina. The cancer center comprises more than 100 faculty cancer scientists and 20 academic departments. It has an annual research funding portfolio of more than $44 million and a dedication to reducing the cancer burden in South Carolina. Hollings offers state-of-the-art diagnostic capabilities, therapies and surgical techniques within multidisciplinary clinics that include surgeons, medical oncologists, radiation therapists, radiologists, pathologists, psychologists and other specialists equipped for the full range of cancer care, including more than 200 clinical trials. For more information, visit http://www.hollingscancercenter.org.