When Whitney Goldner, MD, came to the University of Colorado Anschutz School of Medicine from the University of Nebraska Medical Center in 2024, she brought along her experience researching the association between herbicides and endocrine diseases like thyroid cancer.
It’s a connection Goldner saw in her patient population in Nebraska, and she says it’s a similar story in Colorado, where there is a large rural population that comes to urban centers like CU Anschutz for their care.
“Many studies have been done that make associations between exposures and disease incidence, and we were able to show that there's an increased occurrence of thyroid dysfunction with specific herbicides and pesticides,” says Goldner, head of the Division of Endocrinology, Metabolism and Diabetes. “In Nebraska, we took county-level information about cancer and superimposed data on herbicide usage — how much is bought and applied in those specific counties — and found associations between specific-use herbicides and where these hotspots of thyroid cancer were.”
Goldner and fellow CU Anschutz Cancer Center researcher Rebecca Schweppe, PhD, are now taking a closer look at one of those herbicides to better understand if exposure to the chemical is correlated with higher incidence of thyroid cancer, and if so, what the mechanism is.
“Because this herbicide is used not just in rural populations, but also in urban populations for lawns and gardens, we wanted to study its potential link between herbicide exposure and thyroid cancer,” Goldner says. “It not only affects farmers and rural populations, but it has the potential to affect all of us because it's used on urban lawns and gardens as well.”
The researchers hypothesize not that exposure to the herbicide creates new thyroid tumors, but that the chemical causes existing slow-growing tumors, which haven’t previously been detected, to grow larger and deadlier more quickly.
“We don't think that it's going to cause a new tumor, but we'll look at that as well,” Schweppe says. “We think it's more likely that if someone has an indolent tumor that might take 20 years to turn into a dangerous tumor, maybe this herbicide is going to accelerate that.”
Schweppe and Goldner recently received an R21 exploratory/developmental grant from the Centers for Disease Control to study the issue — because the grant is aimed at workplace health issues and hazardous environments, the cancer center researchers are specifically studying the effects of the chemical on agricultural workers, who may be exposed to high doses of the herbicide for long periods of time.
“We’ll use in vitro approaches with BRAF-mutant thyroid cells and treat them with these herbicides to see if there’s an increase in growth, survival, and transformation,” Schweppe says. “And if we see those effects with either short- or long-term exposure, we'll look at why it’s happening. Is the herbicide promoting changes in how genes are turned on or off, or is it modifying the genes themselves? At the same time, we will use an in vivo transgenic BRAF-mutant model that mimics indolent tumors to determine whether chronic herbicide exposure accelerates tumor growth and aggressiveness.”
Goldner says autopsy studies show that up to 20% of the population have microscopic thyroid cancers they never knew about during their lifetime. As rates of thyroid cancer detection have tripled over the past three decades, she and Schweppe want to find out if there are herbicides or other chemicals that cause those small tumors to expand.
“Our hypothesis is that if somebody has this pre-existing small cluster of cells that was never going to do anything, but they get chronically exposed to some of these carcinogens or things that promote tumor growth, that might be what is pushing the tumors to develop more,” she says.
“There is some data that shows that people who live in rural communities present with more aggressive disease than people in urban communities,” she adds. “Do they wait longer before they come in? Is it earlier detection? Is it more doctor's visits? We don't know. But across the board, for people to be presenting with more aggressive disease, does make you wonder.”
If a definitive connection between herbicides and thyroid cancer development is discovered, the researchers say, their first step would be to increase prevention efforts — more protective gear, reduced use of the chemical, finding other substances that have a similar effect without promoting cancer. But such a finding also could lead to other research, including looking to see if the mechanism by which the herbicides “turn on” the cancer is able to be targeted by drugs, and taking a similar look at other common herbicides and pesticides to see if they have a similar risk.
“We could start looking at other classes of herbicides, as well as combinations of herbicides and pesticides, the exact same way,” Schweppe says. “If we find the mechanism behind herbicide exposure and thyroid cancer cell growth, we could also test other classes of herbicides and pesticides, alone or in combination. Right now it's proof of concept, but I think that we can simulate what happens out in the real world.”