Investigating the Link Between Forever Chemicals and Cancer

Professor Tongzhang Zheng digs deeper into disease etiology.

PFAS, also known as “forever chemicals,” are substances that we encounter regularly in our food, water, air, and through skin contact. These compounds have been extensively used in consumer and industrial goods since the 1950s, and can be found in everything from nonstick cookware to microwavable popcorn bags to the touchscreens on our phones. Their widespread production, persistence in the environment, resistance to breakdown, and tendency to bioaccumulate, have led to their detection in virtually every human serum sample.

Tongzhang Zheng, professor of epidemiology in the Brown University School of Public Health, focuses on identifying underlying causes of cancer, such as pollutants in the water, air and soil, with an emphasis on the link between PFAS and various human cancers. 

Zheng is quite likely one of the hardest-working researchers in public health today. In collaboration with Harvard University, Vanderbilt University, University of Louisville, the Albert Einstein College of Medicine, East Carolina University, Dana Farber Cancer Institute, Brigham and Women’s Hospital, Lifespan, and Rhode Island Hospital, he is currently conducting studies on kidney, bladder, liver, breast and lung cancers, simultaneously. 

His work is of vital importance as cancer is the second leading cause of death in Rhode Island, with bladder and breast cancer of particular virulence. 

“PFAS differ from insecticides like DDT (dichlorodiphenyltrichloroethane) and industrial  pollutants like PCBs (polychlorinated biphenyls) in their properties and behaviors,” Zheng said. “DDT, for example, is fat-soluble and can be stored in fatty tissues, while PFAS do not accumulate in fat. They circulate in the body, shuttling between the liver and kidney and other organs through blood. These pollutants are endocrine disruptors, can induce reactive oxidative species, and have genotoxic abilities, and thus, could cause a lot of damage to our body.”

Federal regulators and the general public have begun to take notice of the health risks associated with PFAS exposure, even as industrial producers of the chemicals lobby against regulations. 

At the recent Senate hearing on “Examining the Federal response to the risks associated with per- and polyfluoroalkyl substances (PFAS)”, Dr. Linda Birnbaum, the former Director of the National Institute of Environmental Health Sciences, highlighted the importance of the work of Zheng and his teams, stating that their findings “can help regulators make sound, science-based decisions and inform the medical and public health communities about the potential health effects of PFAS exposure.”

In our interview, Professor Zheng discussed his research, the correlation between pollutants and cancer, and its implications for public health, both locally and globally.

What factors do you believe contribute to elevated cancer rates in Rhode Island?

We should start with bladder cancer. It’s quite unique, as we actually have one of the highest rates in the United States. It’s puzzling and we don’t have a clear understanding of the underlying reasons.

We’ve recently initiated a collaborative study between Brown University, Lifespan hospitals and other partners to investigate bladder cancer specifically in Rhode Island, because this disease in Rhode Island is among the highest in the United States over the past few decades.

Unfortunately, the cause behind the high rate of bladder cancer in Rhode Island  remains unknown. But there are some things to consider. Take smoking, for example, which is a common cause of this disease. But Rhode Island is not a state with the highest smoking rates. This discrepancy leads us to suspect other exposures, such as water as a potential factor.

We also know that arsenic pollution in the water supply could potentially be responsible for a portion of bladder cancer cases. But again, Rhode Island does not have the highest well water use rate. Neighboring states like New Hampshire actually have a higher rate of well water usage. So our current on-going epidemiologic study is investigating many factors, trying to understand why bladder cancer rates in Rhode Island are so high.

We are collaborating with Drs. Dragan Golijanin, Howard Safran, Stephen Buka, Karl Kelsey, and many others at both the Lifespan Cancer Institute and the Brown School of Public Health to conduct this epidemiology study to identify the risk factors that might contribute to the elevated rates of bladder cancer in Rhode Island.  

Luckily, the size of Rhode Island’s population and its geography are helping in conducting our research. We are a small state by area, with a dense population. This facilitates face-to-face interviews and the collection of study samples of blood, urine, tissue, water and house dust to thoroughly investigate the potential causes of higher bladder cancer rates in the state. Our goal is to answer why Rhode Island has higher risks of bladder cancer than other states, and then to address the concerns related to environmental pollutants and genetic and epigenetic factors as well.

We are also conducting an epidemiologic study of another urologic cancer–kidney cancer–by collaborating with some of the well-characterized major prospective cohort studies in the US. Some of these studies have been ongoing for decades (since the 1970s and 1980s), following a group of individuals over a long period of time. Studies of these urologic cancers at the same time could shed more light on the risk factors of these diseases.

How do overall cancer rates in Rhode Island compare to the rest of the United States?

Rhode Island has a higher overall age-adjusted cancer incidence rate than the overall US rate. In fact, Rhode Island has higher rates than the national average for most cancers (such as bladder, breast, brain, esophagus, liver, lung, prostate, stomach, thyroid, and uterus). With bladder cancer, however, Rhode Island has the highest rate per capita compared to other US states.

While the war against cancer has been successful (the cancer mortality rate has been declining), we must recognize that several cancers are still increasing in our state and in the US. For example, cancers of the pancreas, liver, breast, testis, adenocarcinoma of kidney and esophagus and cardia have been increasing. 

Some cancers are increasing more rapidly among certain age groups. For example, colon cancer is on the rise among those under age 50. Other cancers are increasing mainly among specific racial subgroups, such as testicular cancer among young white males. 

Obesity may explain part of the increase of kidney cancer, adenocarcinoma of the esophagus and cardia; dietary fat intake may explain part of the increase of colon cancer. Some suggest that long-standing diabetes may be a risk factor for pancreatic cancer and because diabetes is increasing, pancreatic cancer thus increases. I suspect, however, diabetes and pancreatic cancer may actually share some risk factors. This is very similar to the case of cryptorchidism and testicular cancer, that is, some factors may cause both cryptorchidism and testicular cancer rather than cryptorchidism causing testicular cancer.  

Overall, we know very little about observed increases in cancers of the pancreas, liver, testis, kidney and breast. That is the very reason why we are conducting epidemiological studies of these diseases in the US.

How do incidences of diabetes and pancreatic cancer in the United States compare to China?

The United States has a higher rate of both pancreatic cancer and diabetes compared to China. However, China is catching up and its increase in diabetes and pancreatic cancer is mirroring its economic rise. The speed of increase in both diabetes and pancreatic cancer in China is much higher than the global levels. Economic rise itself obviously is not the reason for the observed increase in these and other diseases in China, but the severe environmental pollution during industrialization is possibly the underlying reason. So researchers are looking at industrial and environmental factors, hypothesizing that factors such as pollution and industrial hazards may play a role in the increase of these diseases. 

One particular concern is the presence of PFAS chemicals. PFAS exposure increases oxidative stress and proinflammatory reaction in the pancreas, and heightened inflammation is an important mechanism in the development of diabetes and pancreatic cancer.

PFAS are widespread and persistent in the environment. They have a long half-life and are difficult to break down in our bodies and the environment. Many PFAS are still being produced. However, our understanding of their impact is still in the early stages, and research efforts in the US have been initiated in recent years by government agencies, Congress, and healthcare professionals to investigate the exposure and associated risks of these chemicals.

We call PFAS “forever chemicals” because, in the environment, the sunlight and water cannot break them down; in our body, enzymes cannot break them down.  Our liver and kidneys are unable to process them. So they remain in the environment and within us for a long, long time – that is, forever. 

We call PFAS “forever chemicals” because … they remain in the environment and within us for a long, long time – that is, forever.

Tongzhang Zheng Professor of Epidemiology
Tongzhang Zheng

While we focus on PFAS, we should recognize that many other chemicals are also present in our surroundings and can lead to constant exposure and adverse health effects. These chemicals, like phthalates and bisphonol A, are also prevalent throughout the environment. We may call these “everywhere chemicals.” The human body processes these chemicals very rapidly with a half-life of a few hours. But because they are everywhere, we are constantly exposed to these chemicals and they are being absorbed into our bodies easily. In this unfortunate way, they too become “forever” chemicals. This “forever” means we are forever exposed to these chemicals.

Despite the challenges of “forever and everywhere chemicals,” you sound optimistic. 

Well, it takes a long time and painstaking hard work by scientists from different disciplines to identify the risk factors of diseases. For example, today, we take for granted that tobacco smoking increases the risk of lung cancer. However, if you read the medical magazines published in the 1930s and 1940s, heated debates took place discussing the link between smoking and lung cancer. It took several decades for the Surgeon General of the US to officially recognize the connection in the early 1960s. So, from the 1930s to the 1960s, hundreds of studies were conducted and their results were published, gradually building evidence that tobacco smoking increases the risk of lung cancer. It took time for the scientific community, government and public to accept this fact and take action. 

Similarly, with the studies we’re conducting on PFAS and cancer risks, we are in the early stages of hypothesis testing. It is essential to gather valid data to determine if the alleged relationship between PFAS exposure and various cancer risks is real. As the studies progress and more data becomes available, we will gain a clearer understanding of if and how PFAS chemicals impact human health. It’s a process that requires time and rigorous scientific investigation to draw reliable and valid conclusions. 

We are not seeking to assign blame but rather to uncover the truth. By investigating PFAS as a potential risk factor, we can determine whether they play a significant role in cancer development or if there are other factors at play, and how these factors impact each other in the process of developing the diseases. Once we have established a clear understanding of the risks, we can move forward in addressing and mitigating those risks effectively.