During the American Association for Cancer Research 2021 session Radiation-Induced Cancers and Cancer Survivorship and companion panel discussion, speakers discussed the mechanisms of radiation-induced carcinogenesis, specifically carcinogenesis arising as a consequence of therapy, and the risks associated with common environmental radiation exposures that people experience in everyday life.
A recording of the session and the panel discussion will be available to registered attendees through June 21.
Radiation-induced carcinogenesis: Insights from experimental and epidemiologic investigations
As the number of cancer survivors in the United States continues to grow, so too does the number of therapy-induced malignancies as late complications of cancer therapy, said Jean L. Nakamura, MD, University of California, San Francisco (UCSF).
“Pediatric patients, in particular, have benefited from intensive chemoradiotherapy over the last 40 years, which resulted in marked improvements in survival; however, there have been consequences of this, and therapy-induced malignancies are one of them,” Nakamura said. “We also know from the growing population of adult cancer survivors that therapy-induced malignancies are also a concern for them.”
While cancer patients receive mutagenic therapies from both chemotherapy and radiation therapy, Nakamura said radiation therapy is responsible for most therapy-induced malignancies, noting that solid tumors predominate, although hematopoietic malignancies have been described.
“Radiation-induced cancers are varied and arise from multiple organs. That contributes to the challenge in understanding how to mitigate against a process that can involve such diverse cell types and organs,” she said. “At UCSF, we have been analyzing individual patients to try to understand with better granularity the molecular mechanisms that contribute to their risk.”
In their work, Nakamura and colleagues have developed holistic models allowing them to dissect and test specific mechanisms that contribute to radiation-induced carcinogenesis. One gene that has come under particular focus for them is germline mutations in neurofibromatosis 1 (NF1), one of the most common variants in adult cancers.
As predicted in their mouse models, Nakamura said, an epidemiological study published in 2018 was the first to demonstrate that patients with NF1 abnormalitites are susceptible to radiation-induced carcinogenesis. The study found that the risk of subsequent neoplasms specifically related to therapy was almost threefold higher among those patients who received radiation versus those who did not.
“We recognize now that therapy-induced malignancies are ‘crimes of opportunity,’ meaning that underlying molecular susceptibilities, such as germline mutations, are seized and acted upon,” Nakamura said. “In terms of future directions, I think there is significant value in synergizing experimental and epidemiologic investigations to enable a more complete understanding of how ionizing radiation produces cancer.”
Environmental radiation exposure: Fact vs. fiction
Jason Harris, PhD, Purdue University, discussed both ionizing and non-ionizing radiation sources that people are exposed to in the course of their everyday lives and dispelled some of the myths and misinformation associated with many of them.
“Radiation is ubiquitous in our environment,” Harris said. “There are a number of materials and radioactive sources that are used for many applications, such as energy in the form of nuclear power, and there are a number of consumer products that release radiation. But it’s important to understand that not all radiation is the same, and not all radiation is created equal.”
Two of the most common everyday radiation exposures come through the use of cell phones and Wi-Fi, which Harris said have been the subject of some questionable and controversial reports.
“Cell phones operate at around 900 MHz frequency, and that falls within what we call the radiofrequency (RF) radiation range on the electromagnetic spectrum,” he said. “We do know that cell phones cause relatively high transient specific absorption rates (SARs) in the head; however, if you look at the literature over the past several decades, most studies have found no association between cell phone exposure and cancer.”
Harris said that in 2018 the FDA concluded that there is no proof that cell phones may be harmful, although he noted that there is still not enough information to completely rule out any risk.
“Like cell phones, Wi-Fi also falls in the RF radiation range and, despite the many sources of exposure, the cumulative RF exposure in ordinary environments is a very small fraction of U.S. and international safety limits,” he said. “These are two forms of non-ionizing radiation and the evidence suggests that with normal use, these are not sources of concern when it comes to cancer.”
Among the sources of ionizing radiation, Harris said that environmental exposure to radon is a well-known health risk.
“We have known for some time about the risk of radon, especially in miners, but more recently, about the potential risk of radon in homes,” he said. “Recent residential case-control radon epidemiological studies do support projections from the miner-based studies that the levels of radon commonly found in homes cause lung cancer.”
In 1995, he said the EPA estimated that out of a total of 146,400 lung cancer deaths in 1995, 21,100 (14%) were related to indoor radon exposure. Recent residential radon epidemiological studies, he added, support this estimate.
“We also know that radon is the second most important cause of lung cancer after cigarette smoking and is considered the primary cause of lung cancer in individuals who have never smoked,” Harris said. “We do know that there is risk here, and so it is recommended to check radon levels in residential dwellings and remediate as necessary according to U.S. EPA guidance.”
Another source of ionizing radiation with residential implications, he said, is living near a nuclear power plant.
“As nuclear power plants operate, they do release very small levels of radiation as part of their normal operations—there is direct radiation that comes from the fission process, but there is also radiation that is released in byproducts or waste products,” Harris said. “Even with this though, this is a highly regulated industry with lots of environmental monitoring, and if you look at what is actually released, the nuclear industry is responsible for really less than 0.1 percent of the radiation exposures to Americans.”
He said that studies have failed to show any correlation between cancer risk and normal nuclear power plant operations.