Chemicals that disrupt cancer-related pathways can act at low doses and likely contribute to the cancer burden
More than one in three Americans will be diagnosed with cancer in their lifetimes. Along with genetics, diet, lifestyle and viruses, exposures to toxic chemicals clearly contribute to this epidemic. This means it is critical to get the science and regulation of carcinogens right, but there is growing evidence that we may be overlooking crucial aspects of how combinations of chemicals may cause cancer.
That’s the conclusion of the Halifax Project, a collaboration of researchers from around the world who have just published a series of groundbreaking papers in a special issue of the scientific journal Carcinogenesis.
Current regulatory policy focuses on identifying “complete carcinogens” – single chemicals that can cause cancer all by themselves, but the Halifax Project’s work raises the strong possibility that complete carcinogens may be only the tip of the iceberg. New research is beginning to look at chemicals that are not carcinogenic in and of themselves but can affect normal cells in ways that make them more prone to becoming cancerous. Could exposures to multiple chemicals such as these over time also have the potential to cause cancer?
This simple yet profound hypothesis is being put forward by the Halifax Project’s scientists, who were brought together by the non-profit organization Getting to Know Cancer. Their investigation of the relationship between cancer and low-dose exposures to chemical mixtures may fundamentally shift the way we think about carcinogenesis.
This idea is based on two well-accepted scientific concepts:
- The development of cancer is a multistep process.
- There is a set of aggressive characteristics and processes, called “hallmarks of cancer,” that distinguish cancer cells from normal ones.
The “hallmarks” consist of a spectrum of changes to healthy cells that allow or cause them to divide and grow uncontrollably, eventually developing into cancer. These hallmarks include such factors as the ability of a cell to replicate endlessly and avoid biologically programmed cell death.
The Halifax Project team examined toxicity data on 85 chemicals that can trigger cancer-related hallmark processes to see if they might pose a risk at exposure levels people typically encounter in day-to-day life. Among the substances were phthalates, which are common plasticizers, and several pesticides. What they found was that 59 percent of the chemicals do affect cancer hallmark processes at low doses.
Although the study investigated only a small number of chemicals, the findings suggest that many of the hundreds of substances to which people are commonly exposed to in the environment may be capable of affecting cancer-related processes in human cells.
How great are the risks associated with chemical mixtures? An analysis by the Environmental Working Group found that 23 of the 85 chemicals investigated by Halifax Project scientists have been measured at detectable levels in the bodies of people participating in the nationally representative National Health and Nutrition Examination Survey, which is conducted annually by the Centers for Disease Control and Prevention. Many questions remain, but if cancer in fact results from an accumulation of these “hallmark” processes, it would mean that exposure to multiple chemicals that act on different cellular pathways could likely cause cancer.
It is time to expand the definition of carcinogenesis beyond the idea of a single chemical acting alone. We must begin to consider how combinations of chemicals working in concert and affecting a cell’s functioning in disparate ways may result in cancer.
As the President’s Cancer Panel pointed out in its 2008-2009 annual report, federal environmental laws not only leave many known carcinogens completely unregulated, they also “fail to address the potential hazards of being exposed to combinations of chemicals”.1
This needs to change for society to have any hope of success in preventing cancer.