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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."
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