Ionizing Radiation
CATEGORY: IARC known, NTP known
USED IN: Medical radiological procedures, such as x-rays, CT scans, fluoroscopy; also from nuclear power plants, radionucleotide research, military weapons testing
“More is known about the relationship between radiation dose and cancer risk than any other human carcinogen, and female breast cancer is the best quantified radiation-related cancer.” —Charles E. Land
Overview and Mechanisms
Ionizing radiation is any form of radiation with enough energy to break off electrons from atoms (i.e., to ionize the atoms). This radiation can break the chemical bonds in molecules, including DNA molecules, thereby disturbing their normal functioning. X-rays and gamma rays are the only major forms of radiation with sufficient energy to penetrate and damage body tissue below the surface of the skin.
Among the many sources of ionizing radiation are traditional X-rays, computed tomography (CT) scans, fluoroscopy and other medical radiological procedures. Sources of gamma rays include emissions from nuclear power plants, scientific research involving radionuclides, military weapons testing and nuclear medicine procedures such as bone, thyroid and lung scans (EPA, 2005).
In 2005, the National Toxicology Program classified X-radiation and gamma radiation as known human carcinogens. There is no such thing as a safe dose of radiation (Brenner, 2003; NRPB, 1995). A 2005 National Research Council report confirms this finding, stating that “the risk of cancer proceeds in a linear fashion at lower doses [of ionizing radiation] without a threshold and that the smallest dose has the potential to cause a small increase in risk to humans” (NRC, 2005). Radiation damage to genes is cumulative over a lifetime (Boice, 2001). Repeated low-dose exposures over time may have the same harmful effects as a single high-dose exposure.
Exposure to ionizing radiation is the best- and longest-established environmental cause of human breast cancer in both women and men. Ionizing radiation can increase the risk for breast cancer through a number of different mechanisms, including direct mutagenesis (causing changes in the structure of DNA), genomic instability (increasing the rate of changes in chromosomes, therefore increasing the likelihood of future mutations) (Goldberg, 2003; Morgan, 2003; Wright, 2004), and changes in breast cell microenvironments that can lead to damaged regulation of cell-to-cell interactions within the breast (Barcellos-Hoff, 2005; Tsai, 2005). Ionizing radiation not only affects cells that are directly exposed, but can also alter the DNA, cell growth and cell-cell interactions of neighboring cells, referred to as the “bystander effect” (Little, 2003; Murray, 2007b).
Interactions Between Ionizing Radiation and Other Factors
There are a number of factors that may interact with radiation to increase the potency of its carcinogenic effect. Some of these factors include a woman’s age at exposure, genetic profile, and possibly estrogen levels. As examples:
a. It has been well established in a number of studies of women exposed to military, accidental or medical sources of radiation that children and adolescents who are exposed are more seriously affected in their later risk for breast cancer than are older women (Boice, 2001)..
b. Recent genetic data indicate that women with some gene mutations (e.g., ATM, TP53 and BRCA1/2) are more likely to develop breast cancer and may be especially susceptible to the cancer-inducing effects of exposures to ionizing radiation (Andrieu, 2006; Berrington de Gonzales, 2009a; Turnbull, 2006).
c. Studies using animal and in vitro human breast tumor cell culture models have demonstrated that the effects of radiation on mammary carcinogenesis may be additive with effects of estrogens (Calaf, 2000; Imaoka, 2009; Segaloff, 1971). This is of particular concern given the widespread exposure to estrogen-mimicking chemicals in our environment and the multiple sources of ionizing radiation.
Evidence Linking Ionizing Radiation and Breast Cancer Risk
The link between radiation exposure and breast cancer has been demonstrated in atomic bomb survivors (Land, 1995; Pierce, 1996; Tokunaga, 1994). Rates of breast cancer were highest among women who were younger than age 20 when the United States dropped atomic bombs on Hiroshima and Nagasaki (Land, 1998). In addition, scientists reported a significant association between ionizing radiation exposure and the incidence of male breast cancer in Japanese atomic bomb survivors (Ron, 2005).
Use of X-rays to examine the spine, heart, lungs, ribs, shoulders and esophagus also exposes parts of the breast to radiation. X-rays and fluoroscopy of infants irradiate the whole body (Gofman, 1996). Decades of research have confirmed the link between radiation and breast cancer in women who were irradiated for many different medical conditions, including tuberculosis (MacKenzie, 1965), benign breast disease (Golubicic, 2008; Mattson, 1995), acute postpartum mastitis (Shore, 1986), enlarged thymus (Adams, 2010; Hildreth, 1989), skin hemangiomas (Lundell, 1999), scoliosis (Morin-Doody, 2000), Hodgkin’s disease (Bhatia, 2003; Guibout, 2005; Horwich, 2004; Wahner-Roeller, 2004), non-Hodgkin’s lymphoma (Tward, 2006) and acne (El-Gamal, 2006). Again, evidence from almost all conditions suggests that exposure to ionizing radiation during childhood and adolescence is particularly dangerous with respect to increased risk for breast cancer later in life.
Female radiology technologists who had sustained daily exposure to ionizing radiation demonstrated an increased risk of breast cancer for those women who began working during their teens or, independent of age, working in the field before the 1940s, when exposure levels were substantially higher than they have been in more recent decades (Morin-Doody, 2006; Simon, 2006). The susceptibility of radiologists for later diagnosis of breast cancer may be affected by common variants in particular genes that are involved in the metabolism of circulating estrogens (Sigurdson, 2009). A review and analysis of all existing related studies found that women who work as airline flight attendants had increased levels of breast cancer. Factors that could explain this increase may include lifestyle and reproductive histories as well as increased exposures to cosmic (atmospheric) ionizing radiation (Ballard, 2000).
Medical Radiation: Risks and Benefits
CT Scans
There is considerable evidence that medical X-rays (including mammography, fluoroscopy and CT scans) are an important and controllable cause of breast cancer (Gofman, 1999; Ma, 2008). Although there has been a significant decrease in exposures to ionizing radiation from individual X-rays over the past several decades, a recent report indicates a sevenfold increase in exposure to medical sources of radiation from the mid-1980s through 2006, primarily arising from the increased use of CT scans and nuclear medicine (NCRP, 2009). In 2007, approximately 72 million CT scans were conducted in the United States (Berrington de Gonzales, 2009b). When a CT scan is directed to the chest, the individual receives the equivalent radiation of 30 to 442 chest X-rays (Redberg, 2009). Recent modeling estimates that use of chest CTs and CT angiography in 2007 alone will lead to an additional 5,300 cases of lung and breast cancer within the next two to three decades (Berrington de Gonzales, 2009b). Other modeling suggests that 1 in 150 women who are 20 years old when they undergo CT angiograms of the chest, and 1 in 270 women (total) having the procedure, will subsequently develop cancers of the chest, including breast cancer (Smith-Bindman, 2009).
Mammography
Many experts believe that the low-dose exposures to radiation received as a result of mammography procedures are not sufficient to increase risk for breast cancer. However, damage from lower-energy sources of X-rays, including those delivered by mammography, cannot be predicted by estimating risk from models based on higher doses (Heyes, 2009; Millikan, 2005). Recent evidence indicates that the lower-energy X-rays provided by mammography result in substantially greater damage to DNA than would be predicted by these models. Evidence also suggests that risk of breast cancer caused by exposure to mammography radiation may be greatly underestimated (Heyes, 2009).
As with other risk factors for breast cancer, evidence indicates that both age at exposures and genetic profiles influence the degree of increased risk for disease in women exposed to multiple mammograms. For example, women who had multiple mammograms more than five years prior to diagnosis had an increased risk for breast cancer, but the effect was only statistically significant for women whose first mammograms were before the age of 35 (Ma, 2008).
This age effect is of particular concern, since it is often recommended that women with either of the BRCA mutations begin annual mammography screening at ages 25 to 30. Further complicating this age-related finding are the data now demonstrating that young women with the very mutations that lead them to begin mammography screenings at earlier ages are actually more vulnerable to the cancer-inducing effects of early and repeated exposures to mammograms. This increased vulnerability has been found in women with BRCA mutations (Berrington de Gonzales, 2009a; Jansen-Van der Weide, 2009) as well as in women with other relatively uncommon polymorphisms in genes known to be involved in various steps of DNA repair (Millikan, 2005).
The detrimental risks from mammography might also be heightened in older women, whose breast epithelial cells have gone through several decades of cell division. Cells derived from older women’s breast tissue were more sensitive to the DNA-damaging effects of low-energy radiation, increasing the likelihood of later conversion to cancerous cells (Soler, 2009).
The U.S. Preventive Services Task Force recently recommended against the use of routine mammography screening before the age of 50 (Nelson, 2009; USPSTF, 2009) but supported the use of biennial screening between the ages of 50 and 75. These recommendations were based on models using a number of factors, including positive and negative test results and the psychological consequences on women of those results; number of follow-up imaging procedures and biopsies; actual diagnoses; and, ultimately, mortality rates from breast cancer. Not considered in the analysis was the contribution of radiation from either single or repeated mammograms or other follow-up tests (Nelson, 2009). As women are now facing the need to make their own decisions about whether to undergo routine screening mammography, it is critical that both physicians and women are better educated about mammography’s potential harms, along with its potential benefits (Gotzsche, 2009).
Radiation Therapy
Some studies suggest that doctors and patients should carefully evaluate the risks and benefits of radiation therapy for survivors of early-stage breast cancer, particularly older women. Women older than 55 derive less benefit from radiation therapy in terms of reduced rate of local recurrence (Veronesi, 1999) and may face increased risks of radiation-induced cardiovascular complications (EBGTCG, 2000), as well as secondary cancers such as leukemias and cancers of the lung, esophagus, stomach and breast (Mellemkjaer, 2006; Roychoudhuri, 2004). Using NCI’s Surveillance, Epidemiology and End Results (SEER) data, researchers showed a 16-fold increased relative risk of angiosarcoma of the breast and chest wall following irradiation of a primary breast cancer (Huang, 2001).
More recent data indicate that women younger than 45 who received the higher radiation exposure associated with post-lumpectomy radiotherapy (as compared to post-mastectomy radiation) had a 1.5-fold increase in later contralateral breast cancer diagnoses. This effect was especially prominent in younger women with a significant family history of breast cancer (Hooning, 2007).
