Editor's Note: Although cancer incidence and mortality have decreased in recent years, cancer remains the second leading cause of death in the United States. According to the American Cancer Society, there were about 1,665,540 newly diagnosed cancers and 585,720 deaths in 2014.
The American Cancer Society estimates that environmental factors account for about 75%-80% of cancer cases and deaths in the United States, whereas hereditary factors make up the rest. Although most environmental risks can be attributed to lifestyle factors, such as smoking (30%) and a mixture of poor nutrition, physical inactivity, and obesity (35%), there is still a significant burden from a range of environmental exposures. The International Agency for Research on Cancer (IARC), the World Health Organization's cancer research division, has classified 107 such agents to be carcinogenic to humans; these include tobacco, asbestos, benzene, arsenic, ionizing radiation, and ultraviolet radiation.
But for other environmental exposures or chemicals, the link to cancer remains less clear. In this column, Medscape has investigated five common concerns that people have about environmental cancer risks to determine how robust the link to cancer actually is.
Does BPA Increase Cancer Risk?
What the science says: Determining whether a link between bisphenol A (BPA) and cancer exists has become increasingly important, given the ubiquity of this substance. BPA, which forms the building blocks of polycarbonate plastics and resins, has become one of the highest-volume chemicals produced worldwide. The compound is found in a range of consumer goods, including baby and water bottles, eyeglass lenses, toys, cell phones, and food containers, as well as in the lining of most food and beverage cans. Research from the Centers for Disease Control and Prevention shows that more than 90% of Americans have BPA in their urine,[1]probably because the chemical can leach from bottles and cans.[2,3]
Inquiry into the health effects of synthetic estrogens and other endocrine disruptors began in the late 1960s, when seven young women in Massachusetts were diagnosed with a very rare cancer: clear cell adenocarcinoma of the vagina. This grouping of rare cancers motivated doctors at Massachusetts General Hospital to try to identify a common cause. After an in-depth analysis, the doctors traced the source of the cancer to diethylstilbestrol (DES), a potent synthetic estrogen commonly given to pregnant women because it was thought to help prevent miscarriages. The doctors published their findings in the New England Journal of Medicine in 1971,[4]and shortly thereafter the US Food and Drug Administration (FDA) advised physicians to stop giving DES to pregnant women because of the strong link to cancer.
This initial work spurred scientists to take a closer look at the effects of DES and other endocrine disruptors, such as BPA, on the health of humans and animals. In 1991, experts from an array of disciplines gathered at the Wingspread Conference on the Precautionary Principle to discuss a growing body of evidence pointing to the harmful effects of chemical exposures on human and animal populations. The attendees issued a consensus statement: "We are certain of the following: a large number of man-made chemicals that have been released into the environment, as well as a few natural ones, have the potential to disrupt the endocrine system of animals, including humans."[5]
In 2009, given the weight of the research, the Endocrine Society also issued a scientific statement on the health effects of endocrine disruptors[6]: "Results from animal models, human clinical observations, and epidemiological studies converge to implicate [endocrine-disrupting chemicals] as a significant concern to public health."
In 2010, Ana M. Soto, MD, and Carlos Sonnenschein, MD, biologists at Tufts University School of Medicine in Boston, published a review in Nature Reviews Endocrinology evaluating 30 years' worth of research on whether endocrine disruptors increase the risk of developing breast and prostate cancer.[7] Studies showed, for example, that when pregnant rats are exposed to low doses of BPA, their offspring are more likely to develop precancerous mammary lesions in adulthood.[8] In addition, studies have reported that infant rats exposed to BPA during lactation and treated with a chemical carcinogen at 50 days of age displayed an elevated risk of developing mammary tumors in adulthood compared with animals not exposed to BPA while nursing.[9] Overall, the authors concluded that "Sufficient supporting data have been gathered on the deleterious effects of endocrine disrupting chemicals to warrant immediate action to decrease human and wildlife exposure to these agents."
A subsequent review published in 2013 by Dr Soto and colleagues continued to support previous findings.[10] The growing body of research uncovered compelling evidence that fetal and neonatal BPA exposure in rats increased the risk for mammary cancer later in life. The authors concluded that these data in laboratory animals can probably be extrapolated to humans and that exposure to BPA and other endocrine-disrupting chemicals has probably contributed "to the increase in the incidence of breast cancer observed over recent decades."
Experts have also proposed several possible mechanisms to explain a link between BPA and cancer. A 2012 study found that BPA can promote human breast cancer cell growth,[11] and a 2014 study revealed that fetal exposure to BPA in rats alters the expression of genes that regulate the cell cycle, which in turn may increase the likelihood of developing tumors.[12] The 2014 study also showed that BPA increases the incidence of cancerous lesions in adult rat mammary glands. Another 2014 study found that significantly more mice implanted with human prostate stem cells developed precancerous or cancerous lesions later in life after being exposed to low doses of BPA compared with those who were not exposed.[13] Another theory posits that cancer is due to altered tissue organization, a view that is gaining acceptance and that may better explain a link between BPA and cancer, according to Dr Soto.
Aside from a link to cancer, research also suggests that BPA can promote a range of other health issues, including heart disease, diabetes, obesity, and infertility.[14-16]
Despite the mounting evidence in animal models, a causal link between BPA and cancer risk in humans has not been confirmed. According to the World Health Organization's 2014 World Cancer Report, "Definitive proof of the role of BPA in human cancer induction is likely to remain limited, not least by ethical limits to human experiments."
What the expert says: According to Dr Soto, "If we take the results in animal models together, I think we have enough evidence to conclude that BPA increases the risk for breast and prostate cancer in humans."
Still, uncovering a causal link between BPA exposure and cancer in humans is essentially impossible. "To expose humans on purpose is unethical, so there is a limit to what we can investigate," Dr Soto said. In addition, because almost everyone is exposed to BPA, it would not be feasible to conduct a human study comparing the health effects of BPA in people who are exposed vs those who are not.
"In such a case, we need to extrapolate to humans, because to wait for conclusive evidence in humans would be criminal," Dr Soto said. "Given the strong evidence in rats and mice, it is very likely that humans experience similar effects, because we share the same hormones and receptors."
Dr Soto added, "At some point, we have to question how much knowledge is enough to warrant action. To me, we've passed the point with BPA."
To reduce exposure, Dr Soto recommends avoiding plastics that could contain BPA. "The problem here is that we do not know exactly how pervasive BPA is." For instance, polycarbonate is often used for industrial filtering, so drinking from a glass bottle does not necessarily mean the liquid is BPA-free.
"What we really need is global legislation," Dr Soto said. Lawmakers in France and Denmark have already implemented a policy to ban BPA from all food packaging. Until such regulations are instituted in more countries worldwide, Dr Soto advises people to talk to their local representatives and to take part in the public debate.
Verdict: Plausible to likely, given strong evidence in animal models.
Can Cell Phones Increase Risk for Brain Cancer?
What the science says: Despite 20 years of research investigating a link between mobile phone use and brain cancer, experts remain polarized on the issue. Some assert that an increased risk is unlikely, given that the rates of brain cancer haven't risen significantly enough in the past few decades and that cell phones don't give off powerful enough radiation to damage DNA, whereas others believe that studies at the epidemiologic and cellular levels show convincing evidence of an increased risk and point to data that do show a notable increase in the rate of brain cancer.
During the past two decades, the use of mobile phones has skyrocketed. The International Telecommunication Union estimates that worldwide subscriptions reached almost 7 billion at the end of 2014, making it more pertinent than ever to resolve the debate.
Public concern can be traced to the early days of cell phones. In 1992, David Reynard filed a tort claim against the cell phone manufacturer NEC—the first claim of its kind in the United States—because he believed that his wife, Susan, had developed (and later died of) a brain tumor from using her cell phone. The courts rejected the claim owing to "uncertainty of the evidence," but the investigation helped reveal an important gap in our understanding of the effect cell phones may have on our biology.
As Siddhartha Mukherjee, MD, PhD, assistant professor of medicine in the Division of Medical Oncology at Columbia University and author of The Emperor of All Maladies: A Biography of Cancer, has explained, one of the most difficult challenges in cancer epidemiology is unraveling the relationship between a common exposure, such as cell phones, and a rare form of cancer.
One of the methods of disentangling this relationship is case/control studies, which compare people with and without brain cancer through the lens of their cell phone use. Such epidemiologic studies, however, have not yielded totally consistent results.
In a 2009 article, Michael Kundi, PhD, head of the Institute of Environmental Health of the Medical University of Vienna, reviewed 25 case/control studies conducted in the past 10 years that explored a link between cell phone use and brain tumor risk, two of which evaluated participants for more than 10 years.[17] Overall, Dr Kundi found an increased risk for glioma and acoustic neuroma, but some of the individual study results varied. For instance, a 2005 case/control study found that cell phone use was associated with a decreased risk for high-grade glioma, implying a protective effect, and no elevated risk for low-grade glioma or meningioma,[18] but case/control studies by Lennart Hardell, MD, PhD, an oncologist and professor in the Department of Oncology, University Hospital, Örebro, Sweden, have consistently revealed a significantly increased risk of developing acoustic neuroma, glioma, or meningioma in people using mobile phones for more than 10 years.[19,20]
Dr Kundi concluded his review cautiously, stating that epidemiologic evidence "starts to indicate an increased risk, in particular for brain tumors." He also noted that from a public health standpoint, an increase in brain tumor incidence is problematic, but from an individual perspective, the risk remains low.
In 2010, results of the long-awaited Interphone study—the largest case/control study to date exploring the link between cancer and cell phones—were published.[21]Experts hoped the Interphone study would clarify inconsistencies in the literature, but it seemed to complicate matters further. The study involved researchers from 13 countries over 10 years and included 5117 brain tumor cases and 5634 controls. The authors reported a reduced risk for glioma and meningioma in regular cell phone users, but an elevated risk for glioma in people reporting the greatest exposure to cell phones.
Overall, the Interphone results indicated a systemic flaw in the trial, according to Dr Mukherjee, who wrote in a New York Times article that "it is biologically implausible that these results are simultaneously true: how can regular cell phone use protect against cancer while frequent phone use increases risk?"
In addition, when the study's supplementary data—which were not included in the main results—are examined, a more complex picture emerges. For instance, regular cell phone users displayed a greater risk for glioma on the side of the face where they held their phone.
A 2014 report from Dr Hardell's group, which pooled results from two case/control studies on malignant brain tumors diagnosed from 1997 to 2003 and from 2007 to 2009, found that both mobile and cordless phone use significantly elevated the risk for glioma, especially for people who had used their phones for over 25 years.[22]
Aside from case/control studies, animal and genetic studies represent important avenues of inquiry. Cell phones emit nonionizing radiation, which, unlike ionizing radiation, is not energetic enough to directly cause DNA damage. Cell phones emit radiofrequency energy that typically falls in the range of 450-2700MHz, which is powerful enough to trigger chemical reactions. Research exploring the effects of such radiofrequencies in laboratory animals has generally not supported a link to cancer specifically,[23] yet some studies have indicated that these frequencies are powerful enough to damage brain cells in rats.[24]
The effects of radiofrequency energy, however, may be subtler than can be gleaned from animal studies. The energy from mobile phones may leave an imprint on our cells in ways that indirectly lead to tumors down the road—for instance, by decreasing production of a protein known to protect against cancer or by altering brain chemistry in small but notable ways.
For instance, in a 2011 study published in JAMA, Nora Volkow, MD, a brain researcher and director of the National Institute on Drug Abuse in Bethesda, Maryland, and colleagues attempted to determine whether radiofrequency energy could alter brain activity by placing cell phones next to the ears of 47 participants.[25] Dr Volkow found that just 50 minutes of exposure to an activated cell phone, compared with a deactivated one, increased glucose metabolism in the brain regions closest to the antenna. The investigators concluded that although the study does not provide information regarding potential carcinogenic effects from cell phone use, it does reveal that exposure to cell phones can affect brain function in humans.
Similarly, researchers have found that cell phone radiation can cause numerous changes on the cellular level, but it's unclear whether these changes can be extrapolated to cancer risk in humans.[26] Several studies, for instance, have shown radiation levels from cell phones can alter the structure of chromatin—a complex of DNA and proteins that helps regulate gene expression and prevent DNA damage—but others cannot confirm whether these changes have an impact on cancer risk.[27-29]
What the experts say: According to Véronique Terrasse, a spokesperson for IARC, the cancer research branch of WHO, the agency classifies the radiofrequency electromagnetic fields produced by mobile phones as possibly carcinogenic to humans, on the basis of both epidemiologic and animal studies. The category is considered "group 2B," which means a causal association is considered credible, but chance, bias, or confounding cannot be ruled out.
David Carpenter, MD, a professor of environmental health sciences at the University at Albany, State University of New York, would change the IARC's classification to "likely."
"Studies evaluating individuals who have used cell phones for 10 years or more consistently show that they are more likely to develop a glioma," Dr Carpenter said. Given that brain tumors are slow-growing, "we do not yet know the very long-term effects of energy emissions from cell phones, but the trends suggest that our risk increases the longer we use them."
Denis Henshaw, PhD, emeritus professor and senior research fellow in chemistry (now retired) at the University of Bristol, United Kingdom, agreed with Dr Carpenter that research suggests the link between cell phone use and brain tumor risk is credible, especially for prolonged use. "Although the risk for brain tumors in the individual is small, even a doubling of risk from prolonged mobile phone use is of public health significance. I think that the IARC classification should be elevated to 2A (probable carcinogen)."
Leeka Kheifets, PhD, professor of epidemiology in the University of California, Los Angeles, School of Public Health, thinks that the IARC's characterization of the cell phone cancer risk is probably correct, given the current evidence. "It doesn't look like cell phone use is a major risk factor for brain cancer in adults, which is fairly reassuring," Dr Kheifets said.
Until there is further evidence, it may be wise to err on the side of caution. "This is not something people should freak out about, but there are simple ways to reduce exposure to cell phones, such as using headsets or landlines," Dr Carpenter said. "Limiting exposure is especially important, considering that we encounter a range of radiofrequency fields in our daily lives—from our computer, WiFi signal, and commonly used household appliances, such as microwaves."
Verdict: Plausible. The evidence is mixed, with considerable debate and uncertainty in the field.
Editor's Note: An earlier version of this article suggested the connection between cell phone use and cancer was "compelling"; it now more accurately reflects the inconclusive state of the science.
Can Artificial Sweeteners Cause Cancer?"
What the science says: Fears about the potential carcinogenic effects of artificial sweeteners continue to persist, despite a compelling body of evidence showing that no such link exists.
Concerns emerged more than 40 years ago, after studies indicated that the artificial sweetener cyclamate might be linked to cancer, prompting the FDA to ban its use. These findings also compelled researchers to investigate the potential carcinogenesis of another popular artificial sweetener, saccharin.
In 1977, a study published in Science found an association between saccharin and bladder cancer in rats,[30] spurring the FDA to ban saccharin as well. The FDA lifted the ban, however, after thousands of people wrote letters of protest. But until concerns about saccharin could be resolved, the FDA maintained that all foods containing the sweetener must have a warning label stating that "Use of this product may be hazardous to your health. This product contains saccharin, which has been determined to cause cancer in laboratory animals."
Subsequent studies in rats continued to show an elevated risk for bladder cancer after the animals consumed very high doses of the sugar substitute,[31,32] but results in humans showed no clear evidence of an association.[33] In fact, experts soon found that the mechanism that led to cancers in rats was irrelevant in humans.[34]Specifically, when consumed in high doses, researchers discovered that saccharin changes the composition of rat urine, creating a precipitate. The precipitate can damage the cells lining the bladder, which in turn can promote tumor growth when the cells regenerate. This mechanism, however, is unique to rats.
In a monograph published in the late 1990s, a group of experts at the IARC analyzed the results of 17 case/control studies exploring the link between saccharin and bladder cancer in humans. The IARC concluded that "there is inadequate evidence [emphasis original] in humans for the carcinogenicity of saccharin salts used as sweeteners" and downgraded its original categorization of group 2B (possibly carcinogenic to humans) to group 3 (not classifiable as carcinogenic to humans).
In 2000, the National Toxicology Program of the National Institutes of Health removed saccharin from the list of potential carcinogens. In addition, further studies in humans have continued to find no evidence of a link between saccharin consumption and cancer risk.[35]
The data on the carcinogenic effects of other artificial sweeteners, such as aspartame, have formed the basis for similar conclusions. In 2006, researchers at the National Cancer Institute prospectively investigated the link between aspartame consumption and the risk for malignant brain cancer in 285,079 men and 188,905 women who were part of the NIH-AARP Diet and Health Study of retirees.[36]
Over 5 years, the researchers identified 1888 hematopoietic cancers and 315 malignant gliomas and found that higher levels of aspartame were not associated with an elevated risk for either cancer or their subtypes in both men and women. The authors concluded that their findings "do not support the hypothesis that aspartame increases hematopoietic or brain cancer risk."
In the past 10 years, newer-generation artificial sweeteners, including acesulfame potassium (ACK, Sweet One®, Sunett®), sucralose (Splenda®), and neotame (Newtame®), have become widely available. But before these sweeteners received FDA approval, the FDA performed more than 100 safety studies on each one. According to the National Cancer Institute, "The results of these studies showed no evidence that these sweeteners cause cancer or pose any other threat to human health."
What the expert says: "Although there has been a lot of negative press about artificial sweeteners, there is no evidence that artificial sweeteners cause cancer in humans," said Christine Zoumas, MS, RD, project manager of the Diet and Physical Activity Shared Resource at the University of California, San Diego, Moores Cancer Center.
When a food or color additive is developed, Ms Zoumas explained, it goes through dozens of toxicity, animal, and human studies before being approved. Aspartame, for instance, was first developed in 1965 but wasn't FDA approved until 1981, after undergoing testing for 16 years. Even then, the sweetener was only permitted as an additive in selected products while researchers continued to monitor its effects.
The FDA also establishes an acceptable daily intake for additives—the amount of a product a person can safely consume each day with no side effects, Ms Zoumas noted. For aspartame, for instance, the acceptable daily intake is 50 mg/kg of body weight. That means a 60-kg person can safely consume 3000 mg of aspartame per day, which is equivalent to about 136 packets of Equal or sixteen 12-ounce cans of diet soda.
"The testing for food additives in the United States is very rigorous," Ms Zoumas said. "If there was indeed a link between artificial sweeteners and cancer, these products would be off the shelves."
Verdict: No link.
Do Pesticides Increase Cancer Risk?
What the science says: The relationship between pesticide exposure and cancer risk remains difficult to discern. Farmers and others in the agricultural workforce tend to have lower cancer rates overall, which is largely attributed to their physically active lifestyles and lower smoking rates.[37] Still, certain cancers—primarily lymphoma, multiple myeloma, and prostate cancer—occur in higher frequencies in this population.[38]
Some experts surmise that exposure to pesticides and other chemicals may be a strong contributor to the elevated rates of these specific cancers. Recent data from the Agricultural Health Study (AHS), the longest-running prospective cohort study exploring a potential link between pesticides and cancer, supports evidence of an elevated risk for some cancers, but not for others.[39] After following more than 84,000 pesticide applicators and their wives in Iowa and North Carolina from 1993 to 2006, the researchers reported a significantly lower incidence of cancer overall—specifically for oral, colon, lung, bladder, and kidney cancer—compared with the general populations of those states. But the researchers did find an elevated risk for a range of other cancers, including multiple myeloma, prostate cancer, lip cancer, and certain subtypes of non-Hodgkin lymphoma.
In a follow-up study, the AHS group tried to determine the risk for prostate cancer associated with specific pesticides. The 2013 study published in the American Journal of Epidemiology revealed that four insecticides—fonofos, malathion, terbufos, and aldrin—were associated with significantly increased risk for aggressive prostate cancer in farmers and commercial pesticide applicators.[40]
Two subsequent studies from the AHS group found associations between several commonly used pesticides and an elevated risk for specific cancers. One study reported an association between the pesticides DDT, lindane, permethrin, diazinon, and terbufos and certain subtypes of non-Hodgkin lymphoma,[41] whereas another study reported an elevated risk for colorectal and lung cancer risk in the AHS cohort exposed to acetochlor.[42] The authors of the acetochlor study arrived at a cautious conclusion, however, stating that "due to lack of exposure-response trend, small number of exposed cases, and relatively short time between acetochlor use and cancer development, these findings warrant caution in interpretation and further investigation."
Yet other studies have revealed no discernable link between certain pesticides and cancer risk. A 2012 review of epidemiologic studies did not find evidence of increased cancer risk in people exposed to the popular herbicide glyphosate,[43] and a 2013 review of epidemiologic evidence examining a link between atrazine and cancer risk concluded that "there is no causal association between atrazine and cancer and that occasional positive results can be attributed to bias or chance."[44]
What the experts say: According to Paolo Boffetta, MD, MPH, director of the Institute for Translational Epidemiology and professor in the Division of Hematology and Medical Oncology and the Department of Preventive Medicine at Mount Sinai School of Medicine, "For those with high pesticide exposure levels, the link is very plausible for some cancers, such as lymphoma or myeloma and possibly prostate cancer as well. But for other cancers, I don't think evidence is very strong. For consumers, the low level of exposure probably does not increase cancer risk."
The link between pesticides and cancer risk is complex. All pesticides are tested for general toxicity, and most linked to cancer in animals have been banned. "What we have left are chemicals that do not show an effect in animal models," Dr Boffetta said.
In addition, it is difficult to study the effects of individual pesticides in humans. For instance, farmers and applicators apply a range of chemicals in different combinations, and thus are exposed to many agents over time. "It becomes very challenging to identify people exposed to only one pesticide, and it is therefore difficult to identify which individual pesticide or chemicals may put people at risk," Dr Boffetta said. "I don't think for any specific agent, we can state that there is conclusive evidence it causes cancer, but some studies do show an elevated risk for cancer in those with significant pesticide exposure."
Although Dr Boffetta believes further research is needed to determine a causal link, he thinks it is important to reduce exposure levels overall. "I would recommend lowering exposure where possible, especially for applicators and farmers. For consumers, it may be worth erring on the side of caution, even though their risk is likely to be very low."
Ms Zoumas noted that in consumers, there is no clear association between pesticide exposure and cancer risk. "There does not appear to be a benefit of organic produce," Ms Zoumas said. "It may be more important to wash fruit well and to be careful about specific fruits, known as the 'dirty dozen,' that have higher levels of pesticides."
Verdict: Plausible in people with high exposure levels (farmers and pesticide applicators), but unlikely in consumers with very low levels of exposure.
Do Extremely Low-Frequency Magnetic Fields From Power Lines Increase Cancer Risk?
What the science says: Almost 30 years ago, a study published in the American Journal of Epidemiology reported a higher risk for leukemia in children who lived near power lines.[45] The authors suggested a possible explanation for this could be magnetic fields, sparking concern that emissions from power lines could cause cancer.
Power lines expose people to extremely low-frequency magnetic fields (ELF MFs) generally within the 50- to 60-Hz range. These fields are even less energetic than the nonionizing radiation produced by cell phones. Given the low levels of radiation emitted, ELF MFs have been generally perceived to be harmless.
But after decades of investigation, epidemiologic studies have consistently found associations between ELF MFs at relatively high levels and childhood leukemia. A meta-analysis published in 2000 examined the results of nine studies to determine whether an association between magnetic fields and childhood leukemia did indeed exist.[46] The researchers found that 99.2% of children living with exposure levels below 0.4 microtesla (μT) showed no increased risk, but the 0.8% of children with exposures of 0.4 μT or more had an elevated risk. A second meta-analysis, which pooled data from 15 studies, found that exposure to ELF MFs of at least 0.3 μT was associated with an almost twofold increased risk for childhood leukemia.[47] To put this risk into context, about 1 in 20,000 US children per year is at risk for leukemia, and proximity to a power line may double those odds to 2 in 20,000 per year, according to statistics from the Centers for Disease Control and Prevention.
In 2002, the IARC classified ELF MFs as possibly carcinogenic to humans on the basis of studies of childhood leukemia (group 2B), because the large body of epidemiologic evidence consistently shows an association between ELF MFs and childhood leukemia; however, the mechanism for how ELF MFs could cause childhood leukemia is still not understood. In addition, no animal model for childhood leukemia exists, making the association difficult to study in animals. Such models have been developed only recently, but they have not yet been tested.
After 2002, subsequent epidemiologic analyses have continued to find an association between ELF MFs and childhood leukemia. In a 2010 analysis, Dr Kheifets and colleagues pooled seven studies performed after 2000, which included 10,865 cases and 12,853 controls.[48] In most individual studies and in the combined results, the risk for childhood leukemia increased with greater exposure, but the association was weaker in the most recently conducted studies. Dr Kheifets and her colleagues concluded, "Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukemia."
Still, causality remains uncertain. A 2013 literature review aimed to estimate the cases of childhood leukemia that might be attributable to ELF MF exposure in the European Union, if the association were indeed causal.[49] The researchers mapped out several exposure/response scenarios and estimated that about 50-60 cases of childhood leukemia could be attributed to ELF MF exposure, depending on the model used. This estimate corresponded to about 1.5%-2.0% of all cases of childhood leukemia. The authors concluded that "according to the current state of evidence, residential exposure to ELF MF may contribute to cases of leukemia in children, but this contribution is relatively small and is characterized by considerable uncertainty."
According to the National Cancer Institute, "Overall, these [epidemiologic] analyses suggest that if there is any increase in leukemia risk from magnetic fields, it is restricted to children with the very highest exposure levels."
Regarding a potential mechanism, a 2011 study found that exposure to 50-Hz magnetic fields at 100 µT increased genotoxicity in a human tumor cell line, but also found the rate of DNA repair increased in exposed cells.[50] A subsequent 2014 study from the same group identified cellular changes induced in a human tumor cell line exposed to a 50-Hz magnetic field for 24 hours.[51] Overall, the exposure disturbed the balance in the cell and increased production of chemically reactive molecules. Although the exposure levels in these studies are orders of magnitude above those used in epidemiologic studies, they do start to hint at how magnetic fields may alter cellular activity and potentially induce genomic instability.
What the experts say: "There is consistent epidemiologic evidence for such an association, but support for causality is missing from experimental research," Martin Röösli, PhD, head of the Environmental Exposures and Health Unit, Swiss Tropical and Public Health Institute, Associated Institute of the University of Basel, Switzerland, told Medscape in an email.
According to Dr Kheifets, "Research in this area indicates that there is no increased risk for major cancers, such as breast cancer, from ELF MFs." But, she said, the evidence that remains unresolved is the link to childhood leukemia. "The epidemiologic studies have consistently found an association between childhood leukemia and magnetic fields, but a plausible explanation for this association is lacking—which means it could be due to chance, bias, or other (yet to be identified) factors related to both magnetic fields and childhood leukemia, or it could be a true association. Even if we were to confirm a relationship between ELF MFs and childhood leukemia, the risk appears to be very low."
Dr Henshaw, however, believes that the link to childhood leukemia is a robust one. "When we come to cellular studies, there is extensive evidence of DNA damage in cells exposed to magnetic fields. For instance, recent work shows that low-level MFs can increase the rate at which free radicals are produced in the cell."
Dr Kheifets noted that it's important to resolve this issue, because any factor that may raise the risk for childhood leukemia is important to understand. "What we need now are some novel approaches to really understand the association."
Verdict: Uncertain, according to Dr Kheifets. Very likely, according to Dr Henshaw. The evidence is highly consistent for an increased risk for childhood leukemia at higher-intensity ELF MFs, but a precise mechanism and animal models for leukemia are still needed.
