Do cancer cells give off specific chemical signatures? Are these signatures different from normal cells?
The answer is it depends. First, take a step back from the definitions of "cancer" versus "normal" cell and recognize that cells and tissues can undergo a variety of changes in their growth. A solid cancer/tumor (as its usually defined) is something that grows and invades the surrounding tissue. A spectrum of possible cell growth can be :
normal -> hypertrophy -> hyperplasia or dysplasia -> hamartoma -> benign tumor -> carcinoma in situ -> invasive cancer -> metastais
(this list is NOT suggesting these are the actual steps to cancer, but instead they are useful for the next paragraph):
The point of this list is that from a human perspective we can see something odd happening when we see a tumor, but the view from inside a cancer cell is basically "things are fine, I'm just doing my cell thing".
But, that said… when a tumor grows and cancer cells invade tissues a few things happen which can give rise to differences between cancer cells and normal tissues and which can be detected.
First, it needs energy, and cancer cells often switch to aerobic glycolysis (a phenomenon called the Warburg effect). As the link shows, a special form of labelled glucose can be used to detect this in the body.
Secondly, a tumor invades the surrounding tissue and generates new blood vessels, and so enzymes that break down extracellular matrix are released.
Some tumors over-express and secrete markers (usually proteins) that can be detected. The prostate specific antigen (PSA) and carcinoembryonic antigen are two examples.
Other things secreted by certain tumors may include volatiles that can be detected by dogs.
The challenge with any 'signature' detection is the sensitivity and specificity which often limits the use of tests that show some early promise.
Cancer cells DO have specific changes to their DNA that can be used as very specific signatures for detection. Tumor DNA is shed into the blood and possibly the urine.
Finally, tumor biology overlaps with many aspects of normal biology, including wound healing and pregnancy and this continues to make it challenging to identify tumor specific markers that have high sensitivity and specificity.
Cellular (Cell) Phones
Cellular (cell or mobile) phones first became widely available in the United States in the 1990s. Since then, along with the large and still growing number of cell phone users (both adults and children), the amount of time people spend on their phones has also risen sharply.
Cell phones give off a form of energy known as radiofrequency (RF) waves, so the safety of cell phone use has raised some concerns. The main concerns have focused on whether cell phones might increase the risk of brain tumors or other tumors in the head and neck area, as these areas are closest to where the phone is usually held while talking or listening on a call.
Nanoparticles Harnessed To Track Cancer-cell Changes
The more dots there are, the more accurate a picture you get when you connect them. A new imaging technology could give scientists the ability to simultaneously measure as many as 100 or more distinct features in or on a single cell. In a disease such as cancer, that capability would provide a much better picture of what's going on in individual tumor cells.
A Stanford University School of Medicine team led by Cathy Shachaf, PhD, an instructor in microbiology and immunology, has for the first time used specially designed dye-containing nanoparticles to simultaneously image two features within single cells. Although current single-cell flow cytometry technologies can do up to 17 simultaneous visualizations, this new method has the potential to do far more. The new technology works by enhancing the detection of ultra-specific but very weak patterns, known as Raman signals, that molecules emit in response to light.
In a study to be published April 15 in the online journal PLoS One, the Stanford team was able to simultaneously monitor changes in two intracellular proteins that play crucial roles in the development of cancer. Successful development of the new technique may improve scientists' ability not only to diagnose cancers &mdash for example, by determining how aggressive tumors' constituent cells are &mdash but to eventually separate living, biopsied cancer cells from one another based on characteristics indicating their stage of progression or their degree of resistance to chemotherapeutic drugs. That would expedite the testing of treatments targeting a tumor's most recalcitrant cells, said Shachaf, a cancer researcher who works in a laboratory run by the study's senior author, Garry Nolan, PhD, associate professor of microbiology and immunology and a member of Stanford's Cancer Center.
Cancer starts out in a single cell, and its development is often heralded by changes in the activation levels of certain proteins. In the world of cell biology, one common way for proteins to get activated is through a process called phosphorylation that slightly changes a protein's shape, in effect turning it on.
Two intracellular proteins, Stat1 and Stat6, play crucial roles in the development of cancer. The Stanford team was able to simultaneously monitor changes in phosphorylation levels of both proteins in lab-cultured myeloid leukemia cells. The changes in Stat1 and Stat6 closely tracked those demonstrated with existing visualization methods, establishing proof of principle for the new approach.
While the new technology so far has been used only to view cells on slides, it could eventually be used in a manner similar to flow cytometry, the current state-of-the-art technology, which lets scientists visualize single cells in motion. In flow cytometry, cells are bombarded with laser light as they pass through a scanning chamber. The cells can then be analyzed and, based on their characteristics, sorted and routed to different destinations within the cytometer.
Still, flow cytometry has its limits. It involves tethering fluorescent dye molecules to antibodies, with different colors tied to antibodies that target different molecules. The dye molecules respond to laser light by fluorescing &mdash echoing light at exactly the same wavelength, or color, with which they were stimulated. The fluorescence's strength indicates the abundance of the cell-surface features to which those dyes are now attached. But at some point, the light signals given off by multiple dyes begin to interfere with one another. It is unlikely that the number of distinct features flow cytometry can measure simultaneously will exceed 20 or so.
The new high-tech dye-containing particles used by the Stanford team go a step further. They give off not just single-wavelength fluorescent echoes but also more-complex fingerprints comprising wavelengths slightly different from the single-color beams that lasers emit. These patterns, or Raman signals, occur when energy levels of electrons are just barely modified by weak interactions among the constituent atoms in the molecule being inspected.
Raman signals are emitted all the time by various molecules, but they're ordinarily too weak to detect. To beef up their strength, the Stanford team employed specialized nanoparticles produced by Intel Corp., each with its own distinctive signature. Intel has designed more than 100 different so-called COINs, or composite organic-inorganic nanoparticles: These are essentially sandwiches of dye molecules and atoms of metals such as silver, gold or copper whose reflective properties amplify a dye molecule's Raman signals while filtering out its inherent fluorescent response. The signals are collected and quantified by a customized, automated microscope.
Shachaf anticipates being able to demonstrate simultaneous visualization of nine or 10 COIN-tagged cellular features in the near future and hopes to bring that number to 20 or 30, a new high, before long. "The technology's capacity may ultimately far exceed that number," she added. Some day it could be used for more than 100 features. Meanwhile, another group outside Stanford, now collaborating with the Nolan group, has developed a prototype device that can detect Raman signals in a continuous flow of single cells, analogous to flow cytometry but with higher resolving power, Shachaf said.
The study was funded by the National Cancer Institute's Center for Cancer Nanotechnology Excellence Focused on Therapy Response and by the Flight Attendant Medical Research Institute. Other Stanford contributors were researchers Sailaja Elchuri, PhD, and Dennis Mitchell of the Nolan lab engineering and materials science graduate student Ai Leen Koh and Robert Sinclair, PhD, professor of materials science and engineering.
Electromagnetic Fields and Cancer
Electric and magnetic fields are invisible areas of energy (also called radiation) that are produced by electricity, which is the movement of electrons, or current, through a wire.
An electric field is produced by voltage, which is the pressure used to push the electrons through the wire, much like water being pushed through a pipe. As the voltage increases, the electric field increases in strength. Electric fields are measured in volts per meter (V/m).
A magnetic field results from the flow of current through wires or electrical devices and increases in strength as the current increases. The strength of a magnetic field decreases rapidly with increasing distance from its source. Magnetic fields are measured in microteslas (μT, or millionths of a tesla).
Electric fields are produced whether or not a device is turned on, whereas magnetic fields are produced only when current is flowing, which usually requires a device to be turned on. Power lines produce magnetic fields continuously because current is always flowing through them. Electric fields are easily shielded or weakened by walls and other objects, whereas magnetic fields can pass through buildings, living things, and most other materials.
Electric and magnetic fields together are referred to as electromagnetic fields, or EMFs. The electric and magnetic forces in EMFs are caused by electromagnetic radiation. There are two main categories of EMFs:
- Higher-frequency EMFs, which include x-rays and gamma rays. These EMFs are in the ionizing radiation part of the electromagnetic spectrum and can damage DNA or cells directly.
- Low- to mid-frequency EMFs, which include static fields (electric or magnetic fields that do not vary with time), magnetic fields from electric power lines and appliances, radio waves, microwaves, infrared radiation, and visible light. These EMFs are in the non-ionizing radiation part of the electromagnetic spectrum and are not known to damage DNA or cells directly. Low- to mid-frequency EMFs include extremely low frequency EMFs (ELF-EMFs) and radiofrequency EMFs. ELF-EMFs have frequencies of up to 300 cycles per second, or hertz (Hz), and radiofrequency EMFs range from 3 kilohertz (3 kHz, or 3,000 Hz) to 300 gigahertz (300 GHz, or 300 billion Hz). Radiofrequency radiation is measured in watts per meter squared (W/m 2 ).
The electromagnetic spectrum represents all of the possible frequencies of electromagnetic energy. It ranges from extremely long wavelengths (extremely low frequency exposures such as those from power lines) to extremely short wavelengths (x-rays and gamma rays) and includes both non-ionizing and ionizing radiation.
What are common sources of non-ionizing EMFs?
There are both natural and human-made sources of non-ionizing EMFs. The earth’s magnetic field, which causes the needle on a compass to point North, is one example of a naturally occurring EMF.
Human-made EMFs fall into both the ELF and radiofrequency categories of non-ionizing part of the electromagnetic spectrum. These EMFs can come from a number of sources.
Extremely low frequency EMFs (ELF-EMFs). Sources of ELF-EMFs include power lines, electrical wiring, and electrical appliances such as shavers, hair dryers, and electric blankets.
Radiofrequency radiation. The most common sources of radiofrequency radiation are wireless telecommunication devices and equipment, including cell phones, smart meters, and portable wireless devices, such as tablets and laptop computers (1). In the United States, cell phones currently operate in a frequency range of about 1.8 to 2.2 GHz (2). (For more information about cell phones, see the NCI fact sheet Cell Phones and Cancer Risk.)
Other common sources of radiofrequency radiation include:
- Radio and television signals. AM/FM radios and older VHF/UHF televisions operate at lower radiofrequencies than cell phones. Radio signals are AM (amplitude-modulated) or FM (frequency-modulated). AM radio is used for broadcasting over very long distances, whereas FM radio covers more localized areas. AM signals are transmitted from large arrays of antennas that are placed at high elevation on sites that are off limits to the general public because exposures close to the source can be high. Maintenance workers could receive substantial radiofrequency exposures from AM radio antennas, but the general public would not. FM radio antennas and TV broadcasting antennas, which are much smaller than AM antennas, are generally mounted at the top of high towers. Radiofrequency exposures near the base of these towers are below guideline limits (3), so exposure of the general population is very low. Sometimes small local radio and TV antennas are mounted on the top of a building access to the roof of such buildings is usually controlled.
- Radar, satellite stations, magnetic resonance imaging (MRI) devices, and industrial equipment.These operate at somewhat higher radiofrequencies than cell phones (1).
- Microwave ovens used in homes, which also operate at somewhat higher radiofrequencies than cell phones (1). Microwave ovens are manufactured with effective shielding that has reduced the leakage of radiofrequency radiation from these appliances to barely detectable levels.
- Cordless telephones, which can operate on analogue or DECT (Digital Enhanced Cordless Telecommunications) technology and typically emit radiofrequencies similar to those of cell phones. However, because cordless phones have a limited range and require a nearby base, their signal strengths are generally much lower than those of cell phones (1).
- Cell phone base stations. Antenna towers or base stations, including those for mobile phone networks and for broadcasting for radio and for television, emit various types of radiofrequency energy. Because the majority of individuals in the general population are exposed only intermittently to base stations and broadcast antennas, it is difficult to estimate exposures for a population (4). The strength of these exposures varies based on the population density of the region, the average distance from the source, and the time of day or the day of the week (lower exposures on the weekends or at night) (1). In general, exposures decrease with increasing distance from the source (5). Exposures among maintenance workers have been found to vary depending on their tasks, the type of antenna, and the location of the worker in relation to the source (1). Cumulative exposures of such workers are very difficult to estimate.
- Televisions and computer screens produce electric and magnetic fields at various frequencies, as well as static electric fields. The liquid crystal displays found in some laptop and desktop computers do not produce substantial electric or magnetic fields. Modern computers have conductive screens that reduce static fields produced by the screen to normal background levels.
- Wireless local area networks, commonly known as Wi-Fi. These are specific types of wireless networking systems and an increasingly common source of radiofrequency radiation. Wireless networks use radio waves to connect Wi-Fi–enabled devices to an access point that is connected to the internet, either physically or through some form of data connection. Most Wi-Fi devices operate at radiofrequencies that are broadly similar to cell phones, typically 2.4 to 2.5 GHz, although in recent years Wi-Fi devices that operate at somewhat higher frequencies (5, 5.3, or 5.8 GHz) have appeared (6). Radiofrequency radiation exposure from Wi-Fi devices is considerably lower than that from cell phones (7). Both sources emit levels of radiofrequency radiation that are far below the guideline of 10 W/m 2 as specified by the International Commission on Non-Ionizing Radiation Protection (3).
- Digital electric and gas meters, also known as “smart meters.” These devices, which operate at about the same radiofrequencies as cell phones, transmit information on consumption of electricity or gas to utility companies. Smart meters produce very low level fields that sometimes cannot be distinguished from the total background radiofrequency radiation levels inside a home (8).
For household appliances and other devices used in the home that require electricity, magnetic field levels are highest near the source of the field and decrease rapidly the farther away the user is from the source. Magnetic fields drop precipitously at a distance of about 1 foot from most appliances. For computer screens, at a distance of 12–20 inches from the screen that most persons using computers sit, magnetic fields are similarly dramatically lower.
Why are non-ionizing EMFs studied in relation to cancer?
Power lines and electrical appliances that emit non-ionizing EMFs are present everywhere in homes and workplaces. For example, wireless local networks are nearly always “on” and are increasingly commonplace in homes, schools, and many public places.
No mechanism by which ELF-EMFs or radiofrequency radiation could cause cancer has been identified. Unlike high-energy (ionizing) radiation, EMFs in the non-ionizing part of the electromagnetic spectrum cannot damage DNA or cells directly. Some scientists have speculated that ELF-EMFs could cause cancer through other mechanisms, such as by reducing levels of the hormone melatonin. There is some evidence that melatonin may suppress the development of certain tumors.
Studies of animals have not provided any indications that exposure to ELF-EMFs is associated with cancer (9–12). The few high-quality studies in animals have provided no evidence that Wi-Fi is harmful to health (7).
Although there is no known mechanism by which non-ionizing EMFs could damage DNA and cause cancer, even a small increase in risk would be of clinical importance given how widespread exposure to these fields is.
What have studies shown about possible associations between non-ionizing EMFs and cancer in children?
Numerous epidemiologic studies and comprehensive reviews of the scientific literature have evaluated possible associations between exposure to non-ionizing EMFs and risk of cancer in children (12–14). (Magnetic fields are the component of non-ionizing EMFs that are usually studied in relation to their possible health effects.) Most of the research has focused on leukemia and brain tumors, the two most common cancers in children. Studies have examined associations of these cancers with living near power lines, with magnetic fields in the home, and with exposure of parents to high levels of magnetic fields in the workplace. No consistent evidence for an association between any source of non-ionizing EMF and cancer has been found.
Exposure from power lines. Although a study in 1979 pointed to a possible association between living near electric power lines and childhood leukemia (15), more recent studies have had mixed findings (16–24). Most of these studies did not find an association or found one only for those children who lived in homes with very high levels of magnetic fields, which are present in few residences.
Several studies have analyzed the combined data from multiple studies of power line exposure and childhood leukemia:
- A pooled analysis of nine studies reported a twofold increase in risk of childhood leukemia among children with exposures of 0.4 μT or higher. Less than 1 percent of the children in the studies experienced this level of exposure (25).
- A meta-analysis of 15 studies observed a 1.7-fold increase in childhood leukemia among children with exposures of 0.3 μT or higher. A little more than 3 percent of children in the studies experienced this level of exposure (26).
- More recently, a pooled analysis of seven studies published after 2000 reported a 1.4-fold increase in childhood leukemia among children with exposures of 0.3 μT or higher. However, less than one half of 1 percent of the children in the studies experienced this level of exposure (27).
For the two pooled studies and the meta-analysis, the number of highly exposed children was too small to provide stable estimates of the dose–response relationship. This means that the findings could be interpreted to reflect linear increases in risk, a threshold effect at 0.3 or 0.4 μT, or no significant increase.
The interpretation of the finding of increased childhood leukemia risk among children with the highest exposures (at least 0.3 μT) is unclear.
Exposure from electrical appliances. Another way that children can be exposed to magnetic fields is from household electrical appliances. Although magnetic fields near many electrical appliances are higher than those near power lines, appliances contribute less to a person’s total exposure to magnetic fields because most appliances are used for only short periods of time. And moving even a short distance from most electrical appliances reduces exposure dramatically. Again, studies have not found consistent evidence for an association between the use of household electrical appliances and risk of childhood leukemia (28).
Exposure to Wi-Fi. In view of the widespread use of Wi-Fi in schools, the UK Health Protection Agency (now part of Public Health England) has conducted the largest and most comprehensive measurement studies to assess exposures of children to radiofrequency electromagnetic fields from wireless computer networks (29,30). This agency concluded that radiofrequency exposures were well below recommended maximum levels and that there was “no reason why Wi-Fi should not continue to be used in schools and in other places” (31).
A review of the published literature concluded that the few high-quality studies to date provide no evidence of biological effects from Wi-Fi exposures (6).
Exposure to cell phone base stations. Few studies have examined cancer risk in children living close to cell phone base stations or radio or television transmitters. None of the studies that estimated exposures on an individual level found an increased risk of pediatric tumors (32–34).
Parental exposure and risk in offspring. Several studies have examined possible associations between maternal or paternal exposure to high levels of magnetic fields before conception and/or during pregnancy and the risk of cancer in their future children. The results to date have been inconsistent (35,36). This question requires further evaluation.
Exposure and cancer survival. A few studies have investigated whether magnetic field exposure is associated with prognosis or survival of children with leukemia. Several small retrospective studies of this question have yielded inconsistent results (37–39). An analysis that combined prospective data for more than 3,000 children with acute lymphoid leukemia from eight countries showed that ELF magnetic field exposure was not associated with their survival or risk of relapse (40).
What have studies shown about possible associations between non-ionizing EMFs and cancer in adults?
Many studies have examined the association between non-ionizing EMF exposure and cancer in adults, of which few studies have reported evidence of increased risk (1).
Residential exposures. The majority of epidemiologic studies have shown no relationship between breast cancer in women and exposure to extremely low frequency EMFs (ELF-EMFs) in the home (41–44), although a few individual studies have suggested an association only one reported results that were statistically significant (45).
Workplace exposures to ELF radiation. Several studies conducted in the 1980s and early 1990s reported that people who worked in some electrical occupations that exposed them to ELF radiation (such as power station operators and telephone line workers) had higher-than-expected rates of some types of cancer, particularly leukemia, brain tumors, and male breast cancer (12). Most of the results were based on participants’ job titles and not on actual measurements of their exposures. More recent studies, including some that considered exposure measurements as well as job titles, have generally not shown an increasing risk of leukemia, brain tumors, or female breast cancer with increasing exposure to magnetic fields at work (45–50).
Workplace exposures to radiofrequency radiation. A limited number of studies have evaluated risks of cancer in workers exposed to radiofrequency radiation. A large study of U.S. Navy personnel found no excess of brain tumors among those with a high probability of exposure to radar (including electronics technicians, aviation technicians, and fire control technicians) however, nonlymphocytic leukemia, particularly acute myeloid leukemia, was increased in electronics technicians in aviation squadrons, but not in Navy personnel in the other job categories (51). A case-control study among U.S. Air Force personnel found the suggestion of an increased risk of brain cancer among personnel who maintained or repaired radiofrequency or microwave-emitting equipment (52). A case-control study found the suggestion of an increased risk of death from brain cancer among men occupationally exposed to microwave and/or radiofrequency radiation, with all of the excess risk among workers in electrical and electronics jobs involving design, manufacture, repair, or installation of electrical or electronics equipment (53). There was no evidence that electrical utility workers who were exposed to pulsed electromagnetic fields produced by power lines were more likely to develop brain tumors or leukemia than the general population (54). Employees of a large manufacturer of wireless communication products were not more likely to die from brain tumors or cancers of the hematopoietic or lymphatic system than the general population (55). A large prospective study among police officers in Great Britain found no evidence for an association between radiofrequency EMF exposure from personal radio use and the risk of all cancers combined (56).
What do expert organizations conclude about the cancer risk from EMFs?
In 2002, the International Agency for Research on Cancer (IARC), a component of the World Health Organization, appointed an expert Working Group to review all available evidence on static and extremely low frequency electric and magnetic fields (12). The Working Group classified ELF-EMFs as “possibly carcinogenic to humans,” based on limited evidence from human studies in relation to childhood leukemia. Static electric and magnetic fields and extremely low frequency electric fields were determined “not classifiable as to their carcinogenicity to humans” (12).
In 2015, the European Commission Scientific Committee on Emerging and Newly Identified Health Risks reviewed electromagnetic fields in general, as well as cell phones in particular. It found that, overall, epidemiologic studies of extremely low frequency fields show an increased risk of childhood leukemia with estimated daily average exposures above 0.3 to 0.4 μT, although no mechanisms have been identified and there is no support from experimental studies that explains these findings. It also found that the epidemiologic studies on radiofrequency exposure do not show an increased risk of brain tumors or other cancers of the head and neck region, although the possibility of an association with acoustic neuroma remains open (57).
Where can people find additional information on EMFs?
The National Institute of Environmental Health Sciences (NIEHS) website has information about EMFs and cancer.
The Occupational Safety and Health Administration website has information about workplace exposures to ELF-EMF.
The US Environmental Protection Agency website has information on power lines and other sources of EMF.
The European Commission also has general information on EMF.
The World Health Organization website also has information about EMFs and public health.
International Agency for Research on Cancer. Non-ionizing Radiation, Part 2: Radiofrequency Electromagnetic Fields. Lyon, France: IARC 2013. IARC monographs on the evaluation of carcinogenic risks to humans, Volume 102.
Ahlbom A, Green A, Kheifets L, et al. Epidemiology of health effects of radiofrequency exposure. Environmental Health Perspectives 2004 112(17):1741–1754.
International Commission on Non-Ionizing Radiation Protection. Guidelines for limiting exposure to time-varying electric and magnetic fields (1 Hz to 100 kHz). Health Physics 2010 99(6):818-36. doi: 10.1097/HP.0b013e3181f06c86.
Schüz J, Mann S. A discussion of potential exposure metrics for use in epidemiological studies on human exposure to radiowaves from mobile phone base stations. Journal of Exposure Analysis and Environmental Epidemiology 2000 10(6 Pt 1):600-5.
Viel JF, Clerc S, Barrera C, et al. Residential exposure to radiofrequency fields from mobile phone base stations, and broadcast transmitters: A population-based survey with personal meter. Occupational and Environmental Medicine 2009 66(8):550-6.
Foster KR, Moulder JE. Wi-Fi and health: review of current status of research. Health Physics 2013 105(6):561-75.
AGNIR. 2012. Health effects from radiofrequency electromagnetic fields. Report from the Independent Advisory Group on Non-Ionising Radiation. In Documents of the Health Protection Agency R, Chemical and Environmental Hazards. RCE 20, Health Protection Agency, UK (Ed.).
Foster KR, Tell RA. Radiofrequency energy exposure from the Trilliant smart meter. Health Physics 2013 105(2):177-86.
Lagroye I, Percherancier Y, Juutilainen J, De Gannes FP, Veyret B. ELF magnetic fields: Animal studies, mechanisms of action. Progress in Biophysics and Molecular Biology 2011 107(3):369-373.
Boorman GA, McCormick DL, Findlay JC, et al. Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in F344/N rats. Toxicologic Pathology 1999 27(3):267-78.
McCormick DL, Boorman GA, Findlay JC, et al. Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in B6C3F1 mice. Toxicologic Pathology 19992 7(3):279-85.
World Health Organization, International Agency for Research on Cancer. Non-ionizing radiation, Part 1: Static and extremely low-frequency (ELF) electric and magnetic fields. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 2002 80:1-395.
Ahlbom IC, Cardis E, Green A, et al. Review of the epidemiologic literature on EMF and Health. Environmental Health Perspectives 2001 109 Suppl 6:911-933.
Schüz J. Exposure to extremely low-frequency magnetic fields and the risk of childhood cancer: Update of the epidemiological evidence. Progress in Biophysics and Molecular Biology 2011 107(3):339-342.
Wertheimer N, Leeper E. Electrical wiring configurations and childhood cancer. American Journal of Epidemiology 1979 109(3):273-284.
Kleinerman RA, Kaune WT, Hatch EE, et al. Are children living near high-voltage power lines at increased risk of acute lymphoblastic leukemia? American Journal of Epidemiology 2000 151(5):512-515.
Kroll ME, Swanson J, Vincent TJ, Draper GJ. Childhood cancer and magnetic fields from high-voltage power lines in England and Wales: A case–control study. British Journal of Cancer 2010 103(7):1122-1127.
Wünsch-Filho V, Pelissari DM, Barbieri FE, et al. Exposure to magnetic fields and childhood acute lymphocytic leukemia in São Paulo, Brazil. Cancer Epidemiology 2011 35(6):534-539.
Sermage-Faure C, Demoury C, Rudant J, et al. Childhood leukaemia close to high-voltage power lines--the Geocap study, 2002-2007. British Journal of Cancer 2013 108(9):1899-1906.
Kabuto M, Nitta H, Yamamoto S, et al. Childhood leukemia and magnetic fields in Japan: A case–control study of childhood leukemia and residential power-frequency magnetic fields in Japan. International Journal of Cancer 2006 119(3):643-650.
Linet MS, Hatch EE, Kleinerman RA, et al. Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. New England Journal of Medicine 1997 337(1):1-7.
Kheifets L, Ahlbom A, Crespi CM, et al. A pooled analysis of extremely low-frequency magnetic fields and childhood brain tumors. American Journal of Epidemiology 2010 172(7):752-761.
Mezei G, Gadallah M, Kheifets L. Residential magnetic field exposure and childhood brain cancer: A meta-analysis. Epidemiology 2008 19(3):424-430.
Does M, Scélo G, Metayer C, et al. Exposure to electrical contact currents and the risk of childhood leukemia. Radiation Research 2011 175(3):390-396.
Ahlbom A, Day N, Feychting M, et al. A pooled analysis of magnetic fields and childhood leukaemia. British Journal of Cancer 2000 83(5):692-698.
Greenland S, Sheppard AR, Kaune WT, Poole C, Kelsh MA. A pooled analysis of magnetic fields, wire codes, and childhood leukemia. Childhood Leukemia-EMF Study Group. Epidemiology 2000 11(6):624-634.
Kheifets L, Ahlbom A, Crespi CM, et al. Pooled analysis of recent studies on magnetic fields and childhood leukaemia. British Journal of Cancer 2010 103(7):1128-1135.
Hatch EE, Linet MS, Kleinerman RA, et al. Association between childhood acute lymphoblastic leukemia and use of electrical appliances during pregnancy and childhood. Epidemiology 1998 9(3):234-245.
Findlay RP, Dimbylow PJ. SAR in a child voxel phantom from exposure to wireless computer networks (Wi-Fi). Physics in Medicine and Biology 2010 55(15):N405-11.
Peyman A, Khalid M, Calderon C, et al. Assessment of exposure to electromagnetic fields from wireless computer networks (wi-fi) in schools results of laboratory measurements. Health Physics 2011 100(6):594-612.
Public Health England. Wireless networks (wi-fi): radio waves and health. Guidance. Published November 1, 2013. Available at https://www.gov.uk/government/publications/wireless-networks-wi-fi-radio-waves-and-health/wi-fi-radio-waves-and-health. (accessed March 4, 2016)
Ha M, Im H, Lee M, et al. Radio-frequency radiation exposure from AM radio transmitters and childhood leukemia and brain cancer. American Journal of Epidemiology 2007 166(3):270-9.
Merzenich H, Schmiedel S, Bennack S, et al. Childhood leukemia in relation to radio frequency electromagnetic fields in the vicinity of TV and radio broadcast transmitters. American Journal of Epidemiology 2008 168(10):1169-78.
Elliott P, Toledano MB, Bennett J, et al. Mobile phone base stations and early childhood cancers: case-control study. British Medical Journal 2010 340:c3077. doi: 10.1136/bmj.c3077.
Infante-Rivard C, Deadman JE. Maternal occupational exposure to extremely low frequency magnetic fields during pregnancy and childhood leukemia. Epidemiology 2003 14(4):437-441.
Hug K, Grize L, Seidler A, Kaatsch P, Schüz J. Parental occupational exposure to extremely low frequency magnetic fields and childhood cancer: A German case–control study. American Journal of Epidemiology 2010 171(1):27-35.
Svendsen AL, Weihkopf T, Kaatsch P, Schüz J. Exposure to magnetic fields and survival after diagnosis of childhood leukemia: A German cohort study. Cancer Epidemiology, Biomarkers & Prevention 2007 16(6):1167-1171.
Foliart DE, Pollock BH, Mezei G, et al. Magnetic field exposure and long-term survival among children with leukaemia. British Journal of Cancer 2006 94(1):161-164.
Foliart DE, Mezei G, Iriye R, et al. Magnetic field exposure and prognostic factors in childhood leukemia. Bioelectromagnetics 2007 28(1):69-71.
Schüz J, Grell K, Kinsey S, et al. Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia: An international follow-up study. Blood Cancer Journal 2012 2:e98.
Schoenfeld ER, O'Leary ES, Henderson K, et al. Electromagnetic fields and breast cancer on Long Island: A case–control study. American Journal of Epidemiology 2003 158(1):47-58.
London SJ, Pogoda JM, Hwang KL, et al. Residential magnetic field exposure and breast cancer risk: A nested case–control study from a multiethnic cohort in Los Angeles County, California. American Journal of Epidemiology 2003 158(10):969-980.
Davis S, Mirick DK, Stevens RG. Residential magnetic fields and the risk of breast cancer. American Journal of Epidemiology 2002 155(5):446-454.
Kabat GC, O'Leary ES, Schoenfeld ER, et al. Electric blanket use and breast cancer on Long Island. Epidemiology 2003 14(5):514-520.
Kliukiene J, Tynes T, Andersen A. Residential and occupational exposures to 50-Hz magnetic fields and breast cancer in women: A population-based study. American Journal of Epidemiology 2004 159(9):852-861.
Tynes T, Haldorsen T. Residential and occupational exposure to 50 Hz magnetic fields and hematological cancers in Norway. Cancer Causes & Control 2003 14(8):715-720.
Labrèche F, Goldberg MS, Valois MF, et al. Occupational exposures to extremely low frequency magnetic fields and postmenopausal breast cancer. American Journal of Industrial Medicine 2003 44(6):643-652.
Willett EV, McKinney PA, Fear NT, Cartwright RA, Roman E. Occupational exposure to electromagnetic fields and acute leukaemia: Analysis of a case-control study. Occupational and Environmental Medicine 2003 60(8):577-583.
Coble JB, Dosemeci M, Stewart PA, et al. Occupational exposure to magnetic fields and the risk of brain tumors. Neuro-Oncology 2009 11(3):242-249.
Li W, Ray RM, Thomas DB, et al. Occupational exposure to magnetic fields and breast cancer among women textile workers in Shanghai, China. American Journal of Epidemiology 2013 178(7):1038-1045.
Groves FD, Page WF, Gridley G, et al. Cancer in Korean war navy technicians: mortality survey after 40 years. American Journal of Epidemiology 2002 155(9):810-8.
Grayson JK. Radiation exposure, socioeconomic status, and brain tumor risk in the U.S. Air Force: a nested case-control study. American Journal of Epidemiology 1996 143(5):480-486.
Thomas TL, Stolley PD, Stemhagen A, et al. Brain tumor mortality risk among men with electrical and electronics jobs: a case-control study. Journal of the National Cancer Institute 1987 79(2): 233-238.
Armstrong B, Thériault G, Guénel P, et al. Association between exposure to pulsed electromagnetic fields and cancer in electric utility workers in Quebec, Canada, and France. American Journal of Epidemiology 1994 140(9):805-820.
Morgan RW, Kelsh MA, Zhao K, et al. Radiofrequency exposure and mortality from cancer of the brain and lymphatic/hemaopoietic systems. Epidemiology 2000: 11(12):118-127.
Gao H, Aresu M, Vergnaud AC, et al. Personal radio use and cancer risks among 48,518 British police officers and staff from the Airwave Health Monitoring Study. British Journal of Cancer 2018 First published online: December 26, 2018.
SCENIHR. 2015. Scientific Committee on Emerging and Newly Identified Health Risks: Potential health effects of exposure to electromagnetic fields (EMF): http://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_041.pdf, accessed August 15, 2015.
If you would like to reproduce some or all of this content, see Reuse of NCI Information for guidance about copyright and permissions. In the case of permitted digital reproduction, please credit the National Cancer Institute as the source and link to the original NCI product using the original product's title e.g., “Electromagnetic Fields and Cancer was originally published by the National Cancer Institute.”
Want to use this content on your website or other digital platform? Our syndication services page shows you how.
Flow cytometry is often used to test the cells from bone marrow, lymph nodes, and blood samples. It’s very accurate in finding out the exact type of leukemia or lymphoma a person has. It also helps tell lymphomas from non-cancer diseases in the lymph nodes.
A sample of cells from a biopsy, cytology specimen, or blood specimen is treated with special antibodies. Each antibody sticks only to certain types of cells that have the antigens that fit with it. The cells are then passed in front of a laser beam. If the cells now have those antibodies, the laser will make them give off light that’s then measured and analyzed by a computer.
Analyzing cases of suspected leukemia or lymphoma by flow cytometry uses the same principles explained in the section on immunohistochemistry:
- Finding the same substances on the surface of most cells in the sample suggests that they came from a single abnormal cell and are likely to be cancer.
- Finding several different cell types with a variety of antigens means that the sample is less likely to contain leukemia or lymphoma.
Flow cytometry can also be used to measure the amount of DNA in cancer cells (called ploidy). Instead of using antibodies to detect protein antigens, cells can be treated with special dyes that react with DNA.
- If there’s a normal amount of DNA, the cells are said to be diploid.
- If the amount is abnormal, the cells are described as aneuploid. Aneuploid cancers of most (but not all) organs tend to grow and spread faster than diploid ones.
Another use of flow cytometry is to measure the S-phase fraction, which is the percentage of cells in a sample that are in a certain stage of cell division called the synthesis or S phase. The more cells that are in the S-phase, the faster the tissue is growing and the more aggressive the cancer is likely to be.
Cell Phones and Cancer Risk
Why has there been concern that cell phones may cause cancer?
There are two main reasons why people are concerned that cell (or mobile) phones might have the potential to cause certain types of cancer or other health problems: Cell phones emit radiation (in the form of radiofrequency radiation, or radio waves), and cell phone use is widespread. Even a small increase in cancer risk from cell phones would be of concern given how many people use them. Brain and central nervous system cancers have been of particular concern because hand-held phones are used close to the head. Many different kinds of studies have been carried out to try to investigate whether cell phone use is dangerous to human health.
Is the radiation from cell phones harmful?
Cell phones emit radiation in the radiofrequency region of the electromagnetic spectrum. Second-, third-, and fourth-generation cell phones (2G, 3G, 4G) emit radiofrequency in the frequency range of 0.7–2.7 GHz. Fifth-generation (5G) cell phones are anticipated to use the frequency spectrum up to 80 GHz.
These frequencies all fall in the nonionizing range of the spectrum, which is low frequency and low energy. The energy is too low to damage DNA. By contrast, ionizing radiation, which includes x-rays, radon, and cosmic rays, is high frequency and high energy. Energy from ionizing radiation can damage DNA. DNA damage can cause changes to genes that may increase the risk of cancer.
The NCI fact sheet Electromagnetic Fields and Cancer lists sources of radiofrequency radiation. More information about ionizing radiation can be found on the Radiation page.
The human body does absorb energy from devices that emit radiofrequency radiation. The only consistently recognized biological effect of radiofrequency radiation absorption in humans that the general public might encounter is heating to the area of the body where a cell phone is held (e.g., the ear and head). However, that heating is not sufficient to measurably increase body temperature. There are no other clearly established dangerous health effects on the human body from radiofrequency radiation.
Has the incidence of brain and central nervous system cancers changed during the time cell phone use increased?
No. Investigators have studied whether the incidence of brain or other central nervous system cancers (that is, the number of new cases of these cancers diagnosed each year) has changed during the time that cell phone use increased dramatically. These studies found:
- stable incidence rates for adult gliomas in the United States (1), Nordic countries (2) and Australia (3) during the past several decades
- stable incidence rates for pediatric brain tumors in the United States during 1993–2013 (4)
- stable incidence rates for acoustic neuroma (5), which are benign tumors, and meningioma (6), which are usually benign, among US adults since 2009
In addition, studies using cancer incidence data have tested different scenarios (simulations) determining whether the incidence trends are in line with various levels of risk as reported in studies of cell phone use and brain tumors between 1979 and 2008 (7, 8). These simulations showed that many risk changes reported in case-control studies were not consistent with incidence data, implying that biases and errors in the study may have distorted the findings.
Because these studies examine cancer incidence trends over time in populations rather than comparing risk in people who do and don’t use cell phones, their ability to observe potential small differences in risk among heavy users or susceptible populations is limited. Observational/epidemiologic studies—including case–control and cohort studies (described below)—are designed to measure individual exposure to cell phone radiation and ascertain specific health outcomes.
How is radiofrequency radiation exposure measured in studies of groups of people?
Epidemiologic studies use information from several sources, including questionnaires and data from cell phone service providers, to estimate radiofrequency radiation exposure in groups of people. Direct measurements are not yet possible outside of a laboratory setting. Estimates from studies reported to date take into account the following:
- How regularly study participants use cell phones (the number of calls per week or month)
- The age and the year when study participants first used a cell phone and the age and the year of last use (allows calculation of the duration of use and time since the start of use)
- The average number of cell phone calls per day, week, or month (frequency)
- The average length of a typical cell phone call
- The total hours of lifetime use, calculated from the length of typical call times, the frequency of use, and the duration of use
What has research shown about the link between cell phone use and cancer risk?
Researchers have carried out several types of population studies to investigate the possibility of a relationship between cell phone use and the risk of tumors, both malignant (cancerous) and benign (nonmalignant). Epidemiologic studies (also called observational studies) are research studies in which investigators observe groups of individuals (populations) and collect information about them but do not try to change anything about the groups.
Two main types of epidemiologic studies—cohort studies and case-control studies—have been used to examine associations between cell phone use and cancer risk. In a case–control study, cell phone use is compared between people who have tumors and people who don’t. In a cohort study, a large group of people who do not have cancer at the beginning of the study is followed over time and tumor development in people who did and didn’t use cell phones is compared. Cohort studies are limited by the fact that they may only be able to look at cell phone subscribers, who are not necessarily the cell phone users.
The tumors that have been investigated in epidemiologic studies include malignant brain tumors, such as gliomas, as well as benign tumors, such as acoustic neuroma (tumors in the cells of the nerve responsible for hearing that are also known as vestibular schwannomas), meningiomas (usually benign tumors in the membranes that cover and protect the brain and spinal cord), parotid gland tumors (tumors in the salivary glands), skin cancer, and thyroid gland tumors.
Three large epidemiologic studies have examined the possible association between cell phone use and cancer: Interphone, a case–control study the Danish Study, a cohort study and the Million Women Study, another cohort study. These studies have been critically evaluated in reviews reported in 2015 (9) and in 2019 (10). The findings of these studies are mixed, but overall, they do not show an association between cell phone use and cancer (11–22).
Interphone Case–Control Study
How the study was done: This is the largest case–control study of cell phone use and the risk of head and neck tumors. It was conducted by a consortium of researchers from 13 countries. The data came from questionnaires that were completed by study participants in Europe, Israel, Canada, Australia, New Zealand, and Japan.
What the study showed: Most published analyses from this study have shown no increases overall in brain or other central nervous system cancers (glioma and meningioma) related to higher amounts of cell phone use. One analysis showed a statistically significant, although small, increase in the risk of glioma among study participants who spent the most total time on cell phone calls. However, for a variety of reasons the researchers considered this finding inconclusive (11–13).
An analysis of data from all 13 countries reported a statistically significant association between intracranial distribution of tumors within the brain and self-reported location of the phone (14). However, the authors of this study noted that it is not possible to draw firm conclusions about cause and effect based on their findings.
An analysis of data from five Northern European countries showed an increased risk of acoustic neuroma in those who had used a cell phone for 10 or more years (15).
In subsequent analyses of Interphone data, investigators investigated whether tumors were more likely to form in areas of the brain with the highest exposure. One analysis showed no relationship between tumor location and level of radiation (16). However, another found evidence that glioma and, to a lesser extent, meningioma were more likely to develop where exposure was highest (17).
Danish Cohort Study
How the study was done: This cohort study linked billing information from more than 358,000 cell phone subscribers with brain tumor incidence data from the Danish Cancer Registry.
What the study showed: No association was observed between cell phone use and the incidence of glioma, meningioma, or acoustic neuroma, even among people who had been cell phone subscribers for 13 or more years (18–20).
Million Women Cohort Study
How the study was done: This prospective cohort study conducted in the United Kingdom used data obtained from questionnaires that were completed by study participants.
What the study showed: Self-reported cell phone use was not associated with an increased risk of glioma, meningioma, or non-central nervous system tumors. Although the original published findings reported an association with an increased risk of acoustic neuroma (21), this association disappeared after additional years of follow-up of the cohort (22).
Other Epidemiologic Studies
In addition to these three large studies, other, smaller epidemiologic studies have looked for associations between cell phone use and individual cancers in both adults and children. These include:
- Two NCI-sponsored case–control studies, each conducted in multiple US academic medical centers or hospitals between 1994 and 1998 that used data from questionnaires (23) or computer-assisted personal interviews (24). Neither study showed a relationship between cell phone use and the risk of glioma, meningioma, or acoustic neuroma in adults.
- The CERENAT study, another case–control study conducted in multiple areas in France from 2004 to 2006 using data collected in face-to-face interviews using standardized questionnaires (25). This study found no association for either gliomas or meningiomas when comparing adults who were regular cell phone users with non-users. However, the heaviest users had significantly increased risks of both gliomas and meningiomas.
- A pooled analysis of two case–control studies conducted in Sweden that reported statistically significant trends of increasing brain cancer risk for the total amount of cell phone use and the years of use among people who began using cell phones before age 20 (26).
- Another case–control study in Sweden, part of the Interphone pooled studies, did not find an increased risk of brain cancer among long-term cell phone users between the ages of 20 and 69 (27).
- The CEFALO study, an international case–control study of children diagnosed with brain cancer between ages 7 and 19, found no relationship between their cell phone use and risk for brain cancer (28).
- A population-based case–control study conducted in Connecticut found no association between cell phone use and the risk of thyroid cancer (29).
What are the findings from studies of the human body?
Researchers have carried out several kinds of studies to investigate possible effects of cell phone use on the human body. In 2011, two small studies were published that examined brain glucose metabolism in people after they had used cell phones. The results were inconsistent. One study showed increased glucose metabolism in the region of the brain close to the antenna compared with tissues on the opposite side of the brain (30) the other study (31) found reduced glucose metabolism on the side of the brain where the phone was used.
The authors of these studies noted that the results were preliminary and that possible health outcomes from changes in glucose metabolism in humans were unknown. Such inconsistent findings are not uncommon in experimental studies of the physiological effects of radiofrequency electromagnetic radiation in people (11). Some factors that can contribute to inconsistencies across such studies include assumptions used to estimate doses, failure to consider temperature effects, and investigators not being blinded to exposure status.
Another study investigated blood flow in the brain of people exposed to radiofrequency radiation from cell phones and found no evidence of an effect on blood flow in the brain (32).
What are the findings from experiments in laboratory animals?
Early studies involving laboratory animals showed no evidence that radiofrequency radiation increased cancer risk or enhanced the cancer-causing effects of known chemical carcinogens (33–36).
Because of inconsistent findings from epidemiologic studies in humans and the lack of clear data from previous experimental studies in animals, in 1999 the Food and Drug Administration (FDA) nominated radiofrequency radiation exposure associated with cell phone exposures for study in animal models by the US National Toxicology Program (NTP). NTP is an interagency program that coordinates toxicology research and testing across the US Department of Health and Human Services and is headquartered at the National Institute of Environmental Health Sciences, part of NIH.
The NTP studied radiofrequency radiation (2G and 3G frequencies) in rats and mice (37, 38). This large project was conducted in highly specialized labs. The rodents experienced whole-body exposures of 3, 6, or 9 watts per kilogram of body weight for 5 or 7 days per week for 18 hours per day in cycles of 10 minutes on, 10 minutes off. A research overview of the rodent studies, with links to the peer-review summary, is available on the NTP website. The primary outcomes observed were a small number of cancers of Schwann cells in the heart and non-cancerous changes (hyperplasia) in the same tissues for male rats, but not female rats, nor in mice overall.
These experimental findings raise new questions because cancers in the heart are extremely rare in humans. Schwann cells of the heart in rodents are similar to the kind of cells in humans that give rise to acoustic neuromas (also known as vestibular schwannomas), which some studies have suggested are increased in people who reported the heaviest use of cell phones. The NTP plans to continue to study radiofrequency exposure in animal models to provide insights into the biological changes that might explain the outcomes observed in their study.
Another animal study, in which rats were exposed 7 days per week for 19 hours per day to radiofrequency radiation at 0.001, 0.03, and 0.1 watts per kilogram of body weight was reported by investigators at the Italian Ramazzini Institute (39). Among the rats with the highest exposure levels, the researchers noted an increase in heart schwannomas in male rats and nonmalignant Schwann cell growth in the heart in male and female rats. However, key details necessary for interpretation of the results were missing: exposure methods, other standard operating procedures, and nutritional/feeding aspects. The gaps in the report from the study raise questions that have not been resolved.
ICNIRP (an independent nonprofit organization that provides scientific advice and guidance on the health and environmental effects of nonionizing radiation) critically evaluated both studies. It concluded that both followed good laboratory practice, including using more animals than earlier research and exposing the animals to radiofrequency radiation throughout their lifetimes. However, it also identified what it considered major weaknesses in how the studies were conducted and statistically analyzed and concluded that these limitations prevent drawing conclusions about the ability of radiofrequency exposures to cause cancer (40).
Why are the findings from different studies of cell phone use and cancer risk inconsistent?
A few studies have shown some evidence of statistical association of cell phone use and brain tumor risks in humans, but most studies have found no association. Reasons for these discrepancies include the following:
- Recall bias, which can occur when data about prior habits and exposures are collected from study participants using questionnaires administered after diagnosis of a disease in some of the participants. Study participants who have brain tumors, for example, may remember their cell phone use differently from individuals without brain tumors.
- Inaccurate reporting, which can happen when people say that something has happened more often or less often than it actually did. For example, people may not remember how much they used cell phones in a given time period.
- Morbidity and mortality among study participants who have brain cancer. Gliomas are particularly difficult to study because of their high death rate and the short survival of people who develop these tumors. Patients who survive initial treatment are often impaired, which may affect their responses to questions.
- Participation bias, which can happen when people who are diagnosed with brain tumors are more likely than healthy people (known as controls) to enroll in a research study.
- Changing technology. Older studies evaluated radiofrequency radiation exposure from analog cell phones. Today, cell phones use digital technology, which operates at a different frequency and a lower power level than analog phones, and cellular technology continues to change (41).
- Exposure assessment limitations. Different studies measure exposure differently, which makes it difficult to compare the results of different studies (42). Investigations of sources and levels of exposure, particularly in children, are ongoing (43).
- Insufficient follow-up of highly exposed populations. It may take a very long time to develop symptoms after exposure to radiofrequency radiation, and current studies may not yet have followed participants long enough.
- Inadequate statistical power and methods to detect very small risks or risks that affect small subgroups of people specifically
- Chance as an explanation of apparent effects may not have been considered.
What are other possible health effects from cell phone use?
The most consistent health risk associated with cell phone use is distracted driving and vehicle accidents (44, 45). Several other potential health effects have been reported with cell phone use. Neurologic effects are of particular concern in young persons. However, studies of memory, learning, and cognitive function have generally produced inconsistent results (46–49).
What have expert organizations said about the cancer risk from cell phone use?
In 2011, the International Agency for Research on Cancer (IARC), a component of the World Health Organization, appointed an expert working group to review all available evidence on the use of cell phones. The working group classified cell phone use as “possibly carcinogenic to humans,” based on limited evidence from human studies, limited evidence from studies of radiofrequency radiation and cancer in rodents, and inconsistent evidence from mechanistic studies (11).
The working group indicated that, although the human studies were susceptible to bias, the findings could not be dismissed as reflecting bias alone, and that a causal interpretation could not be excluded. The working group noted that any interpretation of the evidence should also consider that the observed associations could reflect chance, bias, or confounding variables rather than an underlying causal effect. In addition, the working group stated that the investigation of brain cancer risk associated with cell phone use poses complex research challenges.
The American Cancer Society’s cell phones page states “It is not clear at this time that RF (radiofrequency) waves from cell phones cause dangerous health effects in people, but studies now being done should give a clearer picture of the possible health effects in the future.”
The National Institute of Environmental Health Sciences (NIEHS) states that the weight of the current scientific evidence has not conclusively linked cell phone use with any adverse health problems, but more research is needed.
The US Food and Drug Administration (FDA) notes that studies reporting biological changes associated with radiofrequency radiation have failed to be replicated and that the majority of human epidemiologic studies have failed to show a relationship between exposure to radiofrequency radiation from cell phones and health problems. FDA, which originally nominated this exposure for review by the NTP in 1999, issued a statement on the draft NTP reports released in February 2018, saying “based on this current information, we believe the current safety limits for cell phones are acceptable for protecting the public health.” FDA and the Federal Communications Commission (FCC) share responsibility for regulating cell phone technologies.
The US Centers for Disease Control and Prevention (CDC) states that no scientific evidence definitively answers whether cell phone use causes cancer.
The Federal Communications Commission (FCC) concludes that currently no scientific evidence establishes a definite link between wireless device use and cancer or other illnesses.
In 2015, the European Commission Scientific Committee on Emerging and Newly Identified Health Risks concluded that, overall, the epidemiologic studies on cell phone radiofrequency electromagnetic radiation exposure do not show an increased risk of brain tumors or of other cancers of the head and neck region (9). The committee also stated that epidemiologic studies do not indicate increased risk for other malignant diseases, including childhood cancer (9).
What studies of cell phone health effects are under way?
A large prospective cohort study of cell phone use and its possible long-term health effects was launched in Europe in March 2010. This study, known as Cohort Study of Mobile Phone Use and Health (or COSMOS), has enrolled approximately 290,000 cell phone users aged 18 years or older to date and will follow them for 20 to 30 years (50, 51).
Participants in COSMOS completed a questionnaire about their health, lifestyle, and current and past cell phone use when they joined the study. This information will be supplemented with information from health records and cell phone records. Research updates are posted to the COSMOS website.
The challenge of this ambitious study is to continue following the participants for a range of health effects over many decades. Researchers will need to determine whether participants who leave the study are somehow different from those who remain throughout the follow-up period.
Although recall bias is minimized in studies such as COSMOS that link participants to their cell phone records, such studies face other problems. For example, it is impossible to know who is using the listed cell phone or whether that individual also places calls using other cell phones. To a lesser extent, it is not clear whether multiple users of a single phone, for example family members who may share a device, will be represented on a single phone company account. Additionally, for many long-term cohort studies, participation tends to decline over time.
Has radiofrequency radiation from cell phone use been associated with cancer risk in children?
There are theoretical considerations as to why the possible risk should be investigated separately in children. Their nervous systems are still developing and, therefore, more vulnerable to factors that may cause cancer. Their heads are smaller than those of adults and consequently have a greater proportional exposure to radiation emitted by cell phones. And, children have the potential of accumulating more years of cell phone exposure than adults.
Thus far, the data from studies in children with cancer do not suggest that children are at increased risk of developing cancer from cell phone use. The first published analysis came from a large case–control study called CEFALO, which was conducted in Europe. The study included children who were diagnosed with brain tumors between 2004 and 2008 at the ages of 7 to 19 years. Researchers did not find an association between cell phone use and brain tumor risk by time since initiation of use, by amount of use, or by the location of the tumor (28).
Several studies that will provide more information are under way. Researchers in Spain are conducting another international case–control study, known as Mobi-Kids, which will include 2,000 young people (aged 10–24 years) with newly diagnosed brain tumors and 4,000 healthy young people.
Which US federal agencies have a role in evaluating the effects of or regulating cell phones?
The National Institutes of Health (NIH), including the National Cancer Institute (NCI), conducts research on cell phone use and the risks of cancer and other diseases.
FDA and FCC share regulatory responsibilities for cell phones. FDA is responsible for testing and evaluating electronic product radiation and providing information for the public about the radiofrequency energy emitted by cell phones. FCC sets limits on the emissions of radiofrequency energy by cell phones and similar wireless products.
Where can I find more information about radiofrequency radiation from my cell phone?
The dose of the energy that people absorb from any source of radiation is estimated using a measure called the specific absorption rate (SAR), which is expressed in watts per kilogram of body weight (52). The SAR decreases very quickly as the distance to the exposure source increases. For cell phone users who hold their phones next to their head during voice calls, the highest exposure is to the brain, acoustic nerve, salivary gland, and thyroid.
The FCC provides information about the SAR of cell phones produced and marketed within the previous 1 to 2 years. Consumers can access this information using the phone’s FCC ID number, which is usually located on the case of the phone, and the FCC’s ID search form. SARs for older phones can be found by checking the phone settings or by contacting the manufacturer.
What can cell phone users do to reduce their exposure to radiofrequency radiation?
FDA has suggested some steps that concerned cell phone users can take to reduce their exposure to radiofrequency radiation (53):
- Reserve the use of cell phones for shorter conversations or for times when a landline phone is not available.
- Use a device with hands-free technology, such as wired headsets, which place more distance between the phone and the head of the user.
Use of wired or wireless headsets reduces the amount of radiofrequency radiation exposure to the head because the phone is not placed against the head (54). Exposures decline dramatically when cell phones are used hands-free.
Inskip PD, Hoover RN, Devesa SS. Brain cancer incidence trends in relation to cellular telephone use in the United States. Neuro-Oncology 2010 12(11):1147–1151.
Deltour I, Johansen C, Auvinen A, et al. Time trends in brain tumor incidence rates in Denmark, Finland, Norway, and Sweden, 1974–2003. Journal of the National Cancer Institute 2009 101(24):1721–1724.
Karipidis K, Elwood M, Benke G, et al. Mobile phone use and incidence of brain tumour histological types, grading or anatomical location: A population-based ecological study. BMJ Open 2018 8(12):e024489.
Withrow DR, Berrington de Gonzalez A, Lam CJ, Warren KE, Shiels MS. Trends in pediatric central nervous system tumor incidence in the United States, 1998–2013. Cancer Epidemiology, Biomarkers & Prevention 2019 28(3):522–530.
Kshettry VR, Hsieh JK, Ostrom QT, Kruchko C, Barnholtz-Sloan JS. Incidence of vestibular schwannomas in the United States. Journal of Neuro-oncology 2015 124(2):223–228.
Lin DD, Lin JL, Deng XY, et al. Trends in intracranial meningioma incidence in the United States, 2004–2015. Cancer Medicine 2019 8(14):6458–6467.
Deltour I, Auvinen A, Feychting M, et al. Mobile phone use and incidence of glioma in the Nordic countries 1979–2008: Consistency check. Epidemiology 2012 23(2):301–307.
Little MP, Rajaraman P, Curtis RE, et al. Mobile phone use and glioma risk: Comparison of epidemiological study results with incidence trends in the United States. British Medical Journal 2012 344:e1147.
SCENIHR. 2015. Scientific Committee on Emerging and Newly Identified Health Risks: Potential health effects of exposure to electromagnetic fields (EMF): http://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_041.pdf, accessed December 7, 2020.
Röösli M, Lagorio S, Schoemaker MJ, Schüz J, Feychting M. Brain and salivary gland tumors and mobile phone use: Evaluating the evidence from various epidemiological study designs. Annual Review of Public Health 2019 40:221–238.
International Agency for Research on Cancer. Non-ionizing Radiation, Part 2: Radiofrequency Electromagnetic Fields. Lyon, France: IARC 2013. IARC monographs on the evaluation of carcinogenic risks to humans, Volume 102.
Cardis E, Richardson L, Deltour I, et al. The INTERPHONE study: Design, epidemiological methods, and description of the study population. European Journal of Epidemiology 2007 22(9):647–664.
The INTERPHONE Study Group. Brain tumour risk in relation to mobile telephone use: Results of the INTERPHONE international case-control study. International Journal of Epidemiology 2010 39(3):675–694.
Grell K, Frederiksen K, Schüz J, et al. The intracranial distribution of gliomas in relation to exposure from mobile phones: Analyses from the INTERPHONE study. American Journal of Epidemiology 2016 184(11):818–828
Schoemaker MJ, Swerdlow AJ, Ahlbom A, et al. Mobile phone use and risk of acoustic neuroma: Results of the Interphone case-control study in five North European countries. British Journal of Cancer 2005 93(7):842–848.
Larjavaara S, Schüz J, Swerdlow A, et al. Location of gliomas in relation to mobile telephone use: A case–case and case–specular analysis. American Journal of Epidemiology 2011 174(1):2–11.
Cardis E, Armstrong BK, Bowman JD, et al. Risk of brain tumours in relation to estimated RF dose from mobile phones: Results from five Interphone countries. Occupational and Environmental Medicine 2011 68(9):631–640.
Johansen C, Boice J Jr, McLaughlin J, Olsen J. Cellular telephones and cancer: A nationwide cohort study in Denmark. Journal of the National Cancer Institute 2001 93(3):203–207.
Schüz J, Jacobsen R, Olsen JH, et al. Cellular telephone use and cancer risk: Update of a nationwide Danish cohort. Journal of the National Cancer Institute 2006 98(23):1707–1713.
Frei P, Poulsen AH, Johansen C, et al. Use of mobile phones and risk of brain tumours: Update of Danish cohort study. British Medical Journal 2011 343:d6387.
Benson VS, Pirie K, Schüz J, et al. Mobile phone use and risk of brain neoplasms and other cancers: Prospective study. International Journal of Epidemiology 2013 42(3): 792–802.
Benson VS, Pirie K, Schüz J, et al. Authors' response to: the case of acoustic neuroma: Comment on mobile phone use and risk of brain neoplasms and other cancers. International Journal of Epidemiology 2014 43(1):275. doi: 10.1093/ije/dyt186
Muscat JE, Malkin MG, Thompson S, et al. Handheld cellular telephone use and risk of brain cancer. JAMA 2000 284(23):3001–3007.
Inskip PD, Tarone RE, Hatch EE, et al. Cellular-telephone use and brain tumors. New England Journal of Medicine 2001 344(2):79–86.
Coureau G, Bouvier G, Lebailly P, et al. Mobile phone use and brain tumours in the CERENAT case–control study. Occupational and Environmental Medicine 2014 71(7):514–522.
Hardell L, Carlberg M, Hansson Mild K. Pooled analysis of case–control studies on malignant brain tumours and the use of mobile and cordless phones including living and deceased subjects. International Journal of Oncology 2011 38(5):1465–1474.
Lönn S, Ahlbom A, Hall P, et al. Long-term mobile phone use and brain tumor risk. American Journal of Epidemiology 2005 161(6):526–535.
Aydin D, Feychting M, Schüz J, et al. Mobile phone use and brain tumors in children and adolescents: A multicenter case–control study. Journal of the National Cancer Institute 2011 103(16):1264–1276.
Luo J, Deziel NC, Huang H, et al. Cell phone use and risk of thyroid cancer: A population-based case–control study in Connecticut. Annals of Epidemiology 2019 29:39–45.
Volkow ND, Tomasi D, Wang GJ, et al. Effects of cell phone radiofrequency signal exposure on brain glucose metabolism. JAMA 2011 305(8):808–813.
Kwon MS, Vorobyev V, Kännälä S, et al. GSM mobile phone radiation suppresses brain glucose metabolism. Journal of Cerebral Blood Flow and Metabolism 2011 31(12):2293–301.
Kwon MS, Vorobyev V, Kännälä S, et al. No effects of short-term GSM mobile phone radiation on cerebral blood flow measured using positron emission tomography. Bioelectromagnetics 2012 33(3):247–256.
Hirose H, Suhara T, Kaji N, et al. Mobile phone base station radiation does not affect neoplastic transformation in BALB/3T3 cells. Bioelectromagnetics 2008 29(1):55–64.
Oberto G, Rolfo K, Yu P, et al. Carcinogenicity study of 217 Hz pulsed 900 MHz electromagnetic fields in Pim1 transgenic mice. Radiation Research 2007 168(3):316–326.
Zook BC, Simmens SJ. The effects of pulsed 860 MHz radiofrequency radiation on the promotion of neurogenic tumors in rats. Radiation Research 2006 165(5):608–615.
Lin JC. Cancer occurrences in laboratory rats from exposure to RF and microwave radiation. IEEE J of electromagnetics, RF, and microwaves in medicine and biology 2017 1(1):2–13.
Gong Y, Capstick M, Kuehn S, et al. Life-time dosimetric assessment for mice and rats exposed in reverberation chambers of the 2-year NTP cancer bioassay study on cell phone radiation. IEEE Transactions on Electromagnetic Compatibility 2017 59(6):1798–1808.
Capstick M, Kuster N, Kuehn S, et al. A radio frequency radiation exposure system for rodents based on reverberation chambers. IEEE Transactions on Electromagnetic Compatibility 2017 59(4):1041–1052.
Falcioni L, Bua L, Tibaldi E, et al. Report of final results regarding brain and heart tumors in Sprague-Dawley rats exposed from prenatal life until natural death to mobile phone radiofrequency field representative of a 1.8 GHz GSM base station environmental emission. Environmental Research 2018 165:496–503.
International Commission on Non-Ionizing Radiation Protection (ICNIRP). ICNIRP note: Critical evaluation of two radiofrequency electromagnetic field animal carcinogenicity studies published in 2018. Health Physics 2020 118(5):525–532.
Ahlbom A, Green A, Kheifets L, et al. Epidemiology of health effects of radiofrequency exposure. Environmental Health Perspectives 2004 112(17):1741–1754.
Sagar S, Dongus S, Schoeni A, et al. Radiofrequency electromagnetic field exposure in everyday microenvironments in Europe: A systematic literature review. Journal of exposure science & environmental epidemiology 2018 28(2):147–160.
Eeftens M, Struchen B, Birks LE, et al. Personal exposure to radio-frequency electromagnetic fields in Europe: Is there a generation gap? Environment International 2018 121(Pt 1):216–226.
Atchley P, Strayer DL. Small screen use and driving safety. Pediatrics 2017 140(Suppl 2):S107–S111.
Llerena LE, Aronow KV, Macleod J, et al. An evidence-based review: Distracted driver. The Journal of Trauma and Acute Care Surgery 2015 78(1):147–152.
Brzozek C, Benke KK, Zeleke BM, Abramson MJ, Benke G. Radiofrequency electromagnetic radiation and memory performance: Sources of uncertainty in epidemiological cohort studies. International Journal of Environmental Research and Public Health 201815(4). pii: E592.
Zhang J, Sumich A, Wang GY. Acute effects of radiofrequency electromagnetic field emitted by mobile phone on brain function. Bioelectromagnetics 2017 38(5):329–338.
Foerster M, Thielens A, Joseph W, Eeftens M, Röösli M. A prospective cohort study of adolescents' memory performance and individual brain dose of microwave radiation from wireless communication. Environmental Health Perspectives 2018 126(7):077007.
Guxens M, Vermeulen R, Steenkamer I, et al. Radiofrequency electromagnetic fields, screen time, and emotional and behavioural problems in 5-year-old children. International Journal of Hygiene and Environmental Health 2019 222(2):188–194.
Schüz J, Elliott P, Auvinen A, et al. An international prospective cohort study of mobile phone users and health (Cosmos): Design considerations and enrolment. Cancer Epidemiology 2011 35(1):37–43.
Toledano MB, Auvinen A, Tettamanti G, et al. An international prospective cohort study of mobile phone users and health (COSMOS): Factors affecting validity of self-reported mobile phone use. International Journal of Hygiene and Environmental Health 2018 b221(1):1–8.
Kühn S, Cabot E, Christ A, Capstick M, Kuster N. Assessment of the radio-frequency electromagnetic fields induced in the human body from mobile phones used with hands-free kits. Physics in Medicine and Biology 2009 54(18):5493–508.
Drugs That Target Metastasis
Recent work has uncovered a group of molecules that act to induce or suppress metastasis without affecting the growth of the primary tumor. Many molecules, termed Metastatic Suppressors, have been identified. These molecules are critical for different stages of metastasis, and may function to inhibit cell death upon loss of cell adhesion, or enhance the ability of cells to migrate through the stroma. Researchers are hopeful that these molecules may prove valuable as anti-cancer/anti-metastasis targets.12
It is important to realize that the majority of current anti-cancer drug studies are conducted using primary or cultured tumor cells, and the efficacy of each drug is measured by its ability to reduce the size of primary tumors or kill cells being grown in laboratories. However, because metastatic suppressors do not affect growth of the primary tumor, it is likely like many potentially useful anti-metastatic drugs have been overlooked. New methods of analyzing the ability of drugs to inhibit metastasis, rather than primary tumor growth, are being developed, and should lead to a useful new class of therapeutic compounds.3
Because metastasis relies on the growth of new blood vessels in both the primary and secondary tumors, drugs that inhibit angiogenesis may inhibit metastasis. Currently, the combination of anti-angiogenesis drugs with chemotherapy / radiation is the most effect treatment. Unfortunately, many tumors become resistant to the anti-angiogenesis treatment, so this is generally not a longterm solution. 5
Current research into inhibiting metastasis is focusing on understanding which step of metastasis is the most amenable to therapy. The identification of metastatic suppressor genes has opened up many exciting new potential targets for preventing and inhibiting this deadly event.
Challenges to the Development of Anti-metastasis Drugs
Finding potential drugs that block metastasis is difficult, but getting those drugs evaluated in humans can be even more difficult. Most clinical trials are designed to find out if drugs can kill cancer cells or prevent tumors from growing. A drug that prevents metastasis may not show either of these two activities. Some researchers feel that it is important to come up with new kinds of clinical trials that would specifically look at the ability of drugs to prevent the spread of cancer.13
Conflict of interest
The authors declare no conflict of interest.
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Radon and Cancer
Radon is a radioactive gas released from the normal decay of the elements uranium, thorium, and radium in rocks and soil. It is an invisible, odorless, tasteless gas that seeps up through the ground and diffuses into the air. In a few areas, depending on local geology, radon dissolves into ground water and can be released into the air when the water is used. Radon gas usually exists at very low levels outdoors. However, in areas without adequate ventilation, such as underground mines, radon can accumulate to levels that substantially increase the risk of lung cancer.
How is the general population exposed to radon?
Radon is present in nearly all air. Everyone breathes in radon every day, usually at very low levels. However, people who inhale high levels of radon are at an increased risk of developing lung cancer.
Radon can enter homes through cracks in floors, walls, or foundations, and collect indoors. It can also be released from building materials, or from water obtained from wells that contain radon. Radon levels can be higher in homes that are well insulated, tightly sealed, and/or built on soil rich in the elements uranium, thorium, and radium. Basement and first floors typically have the highest radon levels because of their closeness to the ground.
How does radon cause cancer?
Radon decays quickly, giving off tiny radioactive particles. When inhaled, these radioactive particles can damage the cells that line the lung. Long-term exposure to radon can lead to lung cancer, the only cancer proven to be associated with inhaling radon. There has been a suggestion of increased risk of leukemia associated with radon exposure in adults and children however, the evidence is not conclusive.
How many people develop lung cancer because of exposure to radon?
Cigarette smoking is the most common cause of lung cancer. Radon represents a far smaller risk for this disease, but it is the second leading cause of lung cancer in the United States. Scientists estimate that 15,000 to 22,000 lung cancer deaths in the United States each year are related to radon.
Exposure to the combination of radon gas and cigarette smoke creates a greater risk of lung cancer than exposure to either factor alone. The majority of radon-related cancer deaths occur among smokers. However, it is estimated that more than 10 percent of radon-related cancer deaths occur among nonsmokers.
How did scientists discover that radon plays a role in the development of lung cancer?
Radon was identified as a health problem when scientists noted that underground uranium miners who were exposed to it died of lung cancer at high rates. The results of miner studies have been confirmed by experimental animal studies, which show higher rates of lung tumors among rodents exposed to high radon levels.
What have scientists learned about the relationship between radon and lung cancer?
Scientists agree that radon causes lung cancer in humans. Recent research has focused on specifying the effect of residential radon on lung cancer risk. In these studies, scientists measure radon levels in the homes of people who have lung cancer and compare them to the levels of radon in the homes of people who have not developed lung cancer.
Researchers have combined and analyzed data from all radon studies conducted in Canada and the United States. By combining the data from these studies, scientists were able to analyze data from thousands of people. The results of this analysis demonstrated a slightly increased risk of lung cancer for individuals with elevated exposure to household radon. This increased risk was consistent with the estimated level of risk based on studies of underground miners.
Techniques to measure a person’s exposure to radon over time have become more precise, thanks to a number of studies carried out in the 1990s and early 2000s.
How can people know if they have an elevated level of radon in their homes?
Testing is the only way to know if a person’s home has elevated radon levels. Indoor radon levels are affected by the soil composition under and around the house, and the ease with which radon enters the house. Homes that are next door to each other can have different indoor radon levels, making a neighbor’s test result a poor predictor of radon risk. In addition, rain or snow, barometric pressure, and other influences can cause radon levels to vary from month to month or day to day, which is why both short- and long-term tests are available.
Short-term detectors measure radon levels for 2 days to 90 days, depending on the device. Long-term tests determine the average concentration for more than 90 days. Because radon levels can vary from day to day and month to month, a long-term test is a better indicator of the average radon level. Both tests are relatively easy to use and inexpensive. A state or local radon official can explain the differences between testing devices and recommend the most appropriate test for a person’s needs and conditions.
The U.S. Environmental Protection Agency (EPA) recommends taking action to reduce radon in homes that have a radon level at or above 4 picocuries per liter (pCi/L) of air. About 1 in 15 U.S. homes is estimated to have radon levels at or above this EPA action level. Scientists estimate that lung cancer deaths could be reduced by 2 to 4 percent, or about 5,000 deaths, by lowering radon levels in homes exceeding the EPA’s action level.
The EPA has more information about residential radon exposure and what people can do about it in the Consumer’s Guide to Radon Reduction.
Where can people find more information about radon?
The National Radon Program Services at Kansas State University is funded by the EPA and aimed at promoting public awareness of radon, increased testing, and the reduction of radon in homes, schools, and buildings. It provides a variety of resources, including the National Radon Hotlines, referrals to state radon programs, radon test kit orders, radon mitigation promotion, and other technical assistance and outreach activities.
Consumers can contact the National Radon Hotline at:
- 1–800–SOS–RADON (1–800–767–7236) to reach an automated system for ordering materials and listen to informational recordings
- 1–800–55–RADON (1–800–557–2366) to contact an information specialist, or by sending an e-mail
More information is also available online from the EPA.
Alavanja MC, Lubin JH, Mahaffey JA, Brownson RC. Residential radon exposure and risk of lung cancer in Missouri. American Journal of Public Health 1999 89(7):1042–1048.
Darby S, Hill D, Doll R. Radon: a likely carcinogen at all exposures. Annals of Oncology 2001 12(10):1341–1351.
Darby S, Hill D, Deo H, et al. Residential radon and lung cancer: detailed results of a collaborative analysis of individual data on 7148 persons with lung cancer and 14,208 persons without lung cancer from 13 epidemiologic studies in Europe. Scandinavian Journal of Work, Environment and Health 2006 32(Suppl 1):1–83. Erratum in Scandinavian Journal of Work, Environment and Health 2007 33(1):80.
Field RW. A review of residential radon case-control epidemiologic studies performed in the United States. Reviews on Environmental Health 2001 16(3):151–167.
Field RW, Steck DJ, Smith BJ, et al. Residential radon gas exposure and lung cancer: the Iowa Radon Lung Cancer Study. American Journal of Epidemiology 2000 151(11):1091–1102.
Frumkin H, Samet JM. Radon. CA: A Cancer Journal for Clinicians 2001 51(6):337–344.
Harley NH, Robbins ES. Radon and leukemia in the Danish study: another source of dose. Health Physics 2009 97(4):343–347.
Krewski D, Lubin JH, Zielinski JM, et al. A combined analysis of North American case-control studies of residential radon and lung cancer. Journal of Toxicology and Environmental Health, Part A 2006 69(7):533–597.
Lagarde F, Falk R, Almrén K, et al. Glass-based radon-exposure assessment and lung cancer risk. Journal of Exposure Analysis and Environmental Epidemiology 2002 12(5):344–354.
Möhner M, Gellissen J, Marsh JW, Gregoratto D. Occupational and diagnostic exposure to ionizing radiation and leukemia risk among German uranium miners. Health Physics 2010 99(3):314–321.
National Research Council. Committee on Health Risks of Exposure to Radon: BEIR VI. Health Effects of Exposure to Radon. Washington, DC: National Academy Press, 1999.
If you would like to reproduce some or all of this content, see Reuse of NCI Information for guidance about copyright and permissions. In the case of permitted digital reproduction, please credit the National Cancer Institute as the source and link to the original NCI product using the original product's title e.g., “Radon and Cancer was originally published by the National Cancer Institute.”
Want to use this content on your website or other digital platform? Our syndication services page shows you how.
Uncovering a key player in metastasis
About 90 percent of cancer deaths are caused by secondary tumors, known as metastases, which spread from the original tumor site.
To become mobile and break free from the original tumor, cancer cells need help from other cells in their environment. Many cells have been implicated in this process, including immune system cells and cells that form connective tissue. Another collaborator in metastasis is platelets, the blood cells whose normal function is to promote blood clotting.
The exact role played by platelets has been unclear, but a new paper from Richard Hynes, the Daniel K. Ludwig Professor for Cancer Research, and colleagues shows that platelets give off chemical signals that induce tumor cells to become more invasive and plant themselves in new locations. The findings, published Nov. 14 in Cancer Cell, may help researchers develop drugs that could prevent cancers from spreading, if they are diagnosed before metastasis occurs.
For many years, cancer biologists believed that platelets helped to promote metastasis by helping the cells to form big clumps, allowing them to get stuck in new locations more easily. However, some suspected they might have a more active role, because they contain many growth factors and cytokines, many of which can stimulate cancerous growth.
Before cancer cells can metastasize, they typically undergo a shift known as the epithelial-mesenchymal transition (EMT). During this shift, cells lose their ability to adhere to each other and begin to migrate away from their original locations.
Myriam Labelle, a postdoc in Hynes' lab and lead author of the Cancer Cell paper, found that cancer cells would undergo this transition if grown in contact with platelets in a lab dish. She then analyzed which genes were being turned on in the metastatic cells and found that genes activated by transforming growth factor beta (TGF-beta, or TGF-b) were very active. TGF-beta was already known to promote EMT. Labelle then went on to show that depletion of TGF-beta from platelets in vivo blocked metastasis.
"This work shows that platelets are not just a shield for circulating cancer cells, but also a traveling kit of pro-invasive stimuli," says Joan Massagué, chair of the cancer biology and genetics program at the Sloan-Kettering Institute, who was not part of this study. "For nearly three decades platelets have been known to be the richest source of TGF-b in the body, yet it is only now that someone realized what an important role platelets play as a TGF-b source in tumor dissemination."
A complex interaction
In further experiments, Labelle found that the cancer cells would not become metastatic if exposed only to TGF-beta, suggesting that they need an additional signal from the platelets.
Platelets release many chemicals other than TGF-beta -- they are "little bags of stickiness and growth factors," designed to promote wound healing, says Hynes, who is a member of the David H. Koch Institute for Integrative Cancer Research at MIT. However, none of those chemicals on its own was enough to promote metastasis. Labelle found that direct physical contact between platelets and tumor cells was necessary for the cells to become metastatic.
Specifically, when platelets come into contact with tumor cells, they somehow activate the NF-kappa-b pathway, which is involved in regulating the immune response to infection. Both of the signals, NF-kappa-b activation and TGF-beta, are necessary for the switch to occur.
While tumor cells receive the initial stimulus to become mobile while still in their original location, Hynes and Labelle suspect that the additional boost they get from platelets once they enter the bloodstream makes it easier for the cells to penetrate the walls of blood vessels into a new tumor site.
White blood cells are also suspected in promoting metastasis, and Labelle is now doing experiments to figure out what their role may be, and how they may work together with platelets. She is also examining how platelets activate the NF-kappa-b pathway in tumor cells.
Better understanding of the signals that tumor cells need to metastasize may help researchers develop drugs that can prevent such metastases from developing. "It's important to understand exactly what platelets are doing, and eventually this could be an opportunity for drugs that would treat metastasis," Labelle says.
Such an approach would be useful for stopping primary tumors or metastases from spreading, but would likely not have much effect on secondary tumors that had already formed.