TUCSON, Ariz. — Researchers at the University of Arizona Mel and Enid Zuckerman College of Public Health found that certain kinds of long-lasting chemicals firefighters are exposed to may affect the activity of genes linked to cancer and other diseases. The findings appear in the journal Environmental Research .
The study is among the first to connect common industrial chemicals called PFAS – per- and polyfluoroalkyl substances – to changes in microRNAs, or miRNAs, which are molecules that act as guardrails to help control gene expression.
PFAS are found in a wide range of products, including upholstery, insulation, electronics, cleaning products, fabrics, non-stick cookware – and firefighting foam and gear. Firefighters can be at higher risk for certain cancers, and exposure to toxic chemicals may be one reason why.
"Firefighters tend to have higher PFAS levels due to their occupational exposures," said first author Melissa Furlong, PhD, an assistant professor of environmental health sciences at the Zuckerman College of Public Health and a member of both the University of Arizona Cancer Center and the Center for Firefighter Health Collaborative Research. "Gene activity can be affected by changes in the environment. We wanted to see the imprint of PFAS exposure on miRNAs and evaluate which ones might be associated with diseases."
The scientists analyzed blood samples from 303 firefighters from six locations across the U.S. to measure levels of nine PFAS and corresponding miRNA activity. Changes in miRNAs can play roles in a range of different diseases, including cancers and neurological disorders.
They found that blood levels of certain PFAS in this group of firefighters were associated with changes in specific miRNA activity. The latter were connected to disease pathways for several cancers, neurological disorders and autoimmune conditions.
Furlong was surprised by the number and range of biological pathways that showed up for some of the PFAS, indicating potentially broad impacts on the human body.
For example, a common PFAS called PFOS, or perfluorooctane sulfonic acid, was associated with lower levels of miR-128-1-5p, a miRNA tied to cancer development. Branched forms of PFOS were linked to changes in five other miRNAs, including some known to play roles in regulating cancer development.
More specifically, Furlong and her team found connections among PFAS-related miRNA changes and biological pathways involved in leukemia and bladder, liver, thyroid and breast cancers. They also found miRNA alterations linked to biological pathways involved in neurological diseases, including Alzheimer's disease, and autoimmune and infectious diseases such as lupus, asthma and tuberculosis.
Furlong noted that while the study didn't show direct disease outcomes, the findings pointed to biological changes that might precede disease. A better understanding of the potential biological effects of these kinds of exposures could help in developing new ways to prevent or reduce long-term health risks.
"Identifying an early miRNA signature could indicate a higher likelihood of certain health outcomes, such as a cancer or another disease," she said. "It could be an early indicator of a biological response that could lead to that health outcome."
Changes to DNA that affect gene activity – but don't alter genes themselves – are known as epigenetic changes. Senior author Jeff Burgess, MD, MPH, has been collaborating with firefighters on health and safety research since 1992, with a focus on cancer risk and prevention since 2015. Some of his previous research with firefighters identified epigenetic changes linked to health risks , including cancer , and provided evidence that helped support the international classification of firefighting as carcinogenic .
"Firefighters have requested research on how their exposures lead to increased risk of cancer," said Burgess, who founded the Center for Firefighter Health Collaborative Research and is a professor at the Zuckerman College of Public Health and a U of A Cancer Center member. "Epigenetic markers provide a measure of cancer risk and can also be used to determine the effectiveness of interventions to reduce cancer risk."
Furlong, Burgess and others are working on long-term follow-up studies with firefighters to find ways to help prevent the development of diseases.
"If epigenetics is the mechanism by which PFAS initially works and then later on results in a range of diseases, then that might mean the miRNA could be a modifiable step," Furlong said. "Pharmaceutical companies are already working on treatments that are focused on epigenetic modifications. We have much more work to do."
The study included participants from two firefighter cancer prevention studies, as well as some from the Tucson Fire Department. Additional co-authors from the Zuckerman College of Public Health include former graduate research associate Tuo Liu, PhD, and Shawn Beitel, research program administration officer for the Firefighter Health Collaborative Research Program. The study is also part of the larger Fire Fighter Cancer Cohort Study .
The work was supported in part by the Federal Emergency Management Agency under award nos. EMW-2014-FP-00200, EMW-2015-FP-00213 and EMW-2018-FP-00086, the National Cancer Institute, a division of the National Institutes of Health, under award no. P30CA023074, and the NIH's National Institute of Environmental Health Sciences under award nos. R00ES028743, P30ES006694 and T32ES007091.
