A number of chemical compounds have been established as human carcinogens, but growing evidence suggests that the net may be much wider than previous believed.
According to a new analysis from the Environmental Working Group (EWG), chemicals not known to cause cancer on their own could potentially trigger cellular changes when combined together.
The EWG publicized its report at a press briefing last week.
Science has not been looking at component parts but only in the realm that "this is benign and this is cancer," William Goodson, MD, PhD, senior scientist at the California Pacific Medical Center Research Institute, in San Francisco, said at the briefing.
Dr Goodson emphasized that carcinogenesis is far more complex than "just flipping a switch" and cancer appears. Instead, the process is a series of "flipped switches" that eventually causes the development of cancer.
"You don't necessarily have to get all of the steps from one type of chemical," he said. "One chemical can cause apoptosis to be suppressed, another chemical can stimulate abnormal cells to grow, another chemical can stimulate new blood vessels, another can cause suppression of the immune system, and so on."
This research demonstrates that chemical testing needs to be conducted from a broader perspective, Dr Goodson noted. "We currently look at them one at a time, or sometimes look at a few at a time if they have similar structures or similar actions."
But to date, no one has tried to assess the carcinogenic potential from a mixture of a wide variety of substances, he explained. "We are really in the unknown at this point."
New Look at Exposures
The EWG analysis examined a series of articles that were published June 22 in the journal Carcinogenesis. Their report, Rethinking Carcinogens, takes a close look at new research on chemical exposures and cancer that was conducted by the Halifax Project of the Canadian nonprofit organization Getting to Know Cancer.
Current regulatory policy has focused on identifying "complete carcinogens," or single agents that cause cancer on their own. Research from the Halifax Project, however, has raised the strong possibility that complete carcinogens may not be the only game in town when it comes to cancer-causing chemicals.
Their hypothesis that chemicals that are not carcinogenic in and of themselves but in combination could trigger carcinogenesis is based on two well-accepted concepts: that the development of cancer is a multistep process, and that there is a spectrum of cellular changes called "hallmarks of cancer" that distinguish malignant cells from normal ones.
The team from the Halifax Project examined toxicity data on 85 chemicals that can trigger cancer-related hallmark processes to evaluate what risk — if any — they might pose at exposure levels typical of day-to-day contact. They found that 59% of the chemicals in their survey did affect cancer hallmark processes at low doses.
Concept Set on Its Heels
Several years ago, the President's Cancer Panel noted in its 2008-2009 annual report that they were "concerned to find that the true burden of environmentally induced cancer has been grossly underestimated."
"With nearly 80,000 chemicals on the market in the United States, many of which are used by millions of Americans in their daily lives and are un- or understudied and largely unregulated, exposure to potential environmental carcinogens is widespread," they wrote.
At the press briefing last week, one of the speakers was a member of the President's Cancer Panel ― Margaret L. Kripke, PhD, who is Vivian L. Smith Chair and professor emerita at the University of Texas MD Anderson Cancer Center, Houston. She said that one of the big questions is figuring out the degree to which environmental toxins contribute to cancer. "Historically, we thought that 6% of all cancers were due to something in the environment, but I think that concept has been set on its heels by the Halifax project."
The report changes what is considered to be a carcinogen, she pointed out.
"Now we have to think much more broadly as to what kind of chemicals are in the environment that can change one step along the process, or what can change the microenvironment of the host to make cancer development more likely to occur," Dr Kripke said.
In their analysis, the EWG found that 23 of the 85 chemicals investigated by the Halifax Project team could be measured at detectable levels in individuals who participated in the National Health and Nutrition Examination Survey, which is conducted annually by the Centers for Disease Control and Prevention (CDC).
Senior EWG scientist Curt DellaValle, PhD, pointed out that the data from the CDC are representative of what the exposures are like in the general population.
"It shows us that we are chronically exposed to these chemicals, and we are just picking them up because none of these people were directly exposed," he said. "We are learning that they are in our body simultaneously."
In other words, the chemicals can be interacting in the body and having cumulative adverse effects even if exposure happens at different points in time, he explained.
"Low-dose chemicals that are not classified as carcinogens by regulatory agencies, and dozens of them are in our body, according to the CDC survey ― and the question is if they are adding to the burden of cancer," Dr DellaValle added.
Approached for comment, Susan Gapstur, MPH, PHD, vice president of epidemiology at the American Cancer Society, noted that "while there has been a considerable body of research on occupational and high-dose exposure to environmental chemicals and cancer risk that has resulted in important regulations to limit these exposures, less is known about low-dose exposures and mixtures of low- dose exposures to the general public."
"The information gained from this comprehensive review by an international team of experts is significant because it addresses the biologic complexity of cancer, informs future research efforts, and ultimately might support improved risk assessment," she said.
EWG. Rethinking Carcinogens. Full text
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Cite this: Chemical Combinations May Be Triggering Cancer - Medscape - Jul 20, 2015.