The new study shows that the risk for glioma was tripled among those using a wireless phone for more than 25 years and that the risk was also greater for those who had started using mobile or cordless phones before age 20 years.

“Doctors should be very concerned by this and discuss precautions with their patients,” study author Lennart Hardell, MD, PhD, professor, Department of Oncology, University Hospital, Örebro, Sweden, told Medscape Medical News.

Such precautions, he said, include using hands-free phones with the “loud speaker” feature and text messaging instead of phoning.

The study was published online October 28 in Pathophysiology.

Pooled Data

The recent worldwide increase in use of wireless communications has resulted in greater exposure to radiofrequency electromagnetic fields (RF-EMF). The brain is the main target of RF-EMF when these phones are used, with the highest exposure being on the same side of the brain where the phone is placed.

The new study pooled data from two case-control studies on histopathologically confirmed malignant brain tumours. The first included patients aged 20 to 80 years diagnosed from 1997 to 2003, and the second included those aged 18 to 75 years diagnosed between 2007 and 2009. Cases came from six oncology centers in Sweden.

Cases were matched with controls of the same sex and approximate age who were randomly drawn from the Swedish Population Registry.

All participants filled out a questionnaire detailing exposure to mobile phones and cordless desktop phones.

The analysis included 1498 cases of malignant brain tumors; the mean age was 52 years. Most patients (92%) had a diagnosis of glioma, and just over half of the gliomas (50.3%) were the most malignant variety — astrocytoma grade IV (glioblastoma multiforme). Also included were 3530 controls, with a mean age of 54 years.

The analysis showed an increased risk for glioma associated with use for more than 1 year of both mobile and cordless phones after adjustment for age at diagnosis, sex, socioeconomic index, and year of diagnosis. The highest risk was for those with the longest latency for mobile phone use over 25 years.

Table. Glioma Risk With Mobile and Cordless Phone Use

The risk was increased the more that wireless phones were used. The odds ratios steadily rose with increasing hours of use.

The risk for glioma was greatest in the most exposed part of the brain. The odds ratios were higher for ipsilateral exposure and for glioma in the temporal and overlapping lobes.

Further, the risk was highest among participants who first used a mobile phone (odds ratio, 1.8) or cordless phone (odds ratio, 2.3) before age 20 years, although the number of cases and controls was relatively small.

Developing Brain

As Dr Hardell explained, children and adolescents are more exposed to RF-EMF than adults because of their thinner skull bone and smaller head and the higher conductivity in their brain tissue. The brain is still developing up to about the age of 20 and until that time it is relatively vulnerable, he said.

There was a higher risk for third-generation (3G) mobile phone use compared with other types, but this was based on short latency and rather low numbers of exposed participants, said the authors. 3G universal global telecommunications system mobile phones emit wide band microwave signals, which “hypothetically” may result in higher biological effects compared to other signals, they write.

Such biological effects, said Dr Hardell, could include an increase in reactive oxygen species, which several articles have linked to cancer. The p53 gene has also been implicated, he said.

The study’s very high participation rate (86% for cases and 87% for controls) makes it unlikely that selection bias influenced the results, said the authors.

Dr Hardell believes the new findings reinforce the message that EF-EMF emissions from wireless phones should be regarded as carcinogenic under International Agency on Research on Cancer (IARC) classifications and that current guidelines for exposure “should be urgently revised” to reflect that.

According to the IARC’s 2013 report, there is a “causal” relationship between use of both mobile and cordless phones and that the risk of glioma is “possible.”

Numerous studies have looked at the link between use of wireless phones and brain tumors. Studies by Dr Hardell and his colleagues dating back to the late 1990s have found a connection with mobile and cordless phones.

But the INTERPHONE study (Int J Epidemiol 2011;39:675-694; Cancer Epidemiol 2011;32:453-464) failed to find strong evidence that mobile phones increase the risk for brain tumors.

In addition, a large prospective study (Int J Epidemiol 2013;42:792-802) found that mobile phone use was not associated with increased incidence of glioma or of meningioma or non–central nervous system cancers in middle-aged British women.

According to Dr Hardell, this last study was limited because it used information at one point in time. “It is not a case-control study and has serious problems with the methods used,” he told Medscape Medical News.

Evidence “Unconvincing”

Reached for a comment, L. Dade Lunsford, MD, Lars Leksell Professor of Neurosurgery, and director, Center for Image Guided Neurosurgery, University of Pittsburgh, Pennsylvania, said the new study provides additional “but as yet unconvincing” evidence of a potential role of cell or cordless phone technologies in the pathogenesis of gliomas.

He noted that some features were not controlled, including ionizing radiation exposure and family history.

As well, he said, the study suffers from recall bias, with results possibly being affected by patients being anxious to solve the question of “why me?”

“It is of interest that the only study that used actual industry data of cell phone use (the Danish study [Lancet Oncol 2011;12:624-626; Rev Environment Health 2012;27:51-58]) was dismissed by the authors as ‘uninformative’,” he said. “Perhaps it was not supportive of the author’s premise.”

Although the study didn’t specify the side of the tumor, Dr Lunsford pointed out that about 90% of the world’s population is right-handed and that most hold their mobile phone to their left ear in order to write with their dominant hand. “One could theorize then that left-sided tumors would predominate with the temporal lobe being most adjacent to the cell phone output.”

Dr Lunsford also commented that both glial and Schwann cells are late-responding tissues and that the oncogenesis of such cells by mobile phone technologies remains unexplained. “If cell phones cause such tumors, why do patients not develop higher rates of ipsilateral basal or squamous cell cancers, or melanomas — these are frequently dividing cell lines that theoretically ought to be even more susceptible.”

While the potential role of cell phones as an additional factor in oncogenesis “can’t be dismissed out of hand,” the use of this technology does save lives, stressed Dr Lunsford.

“Cell phone has provided an amazing safety net for citizens of almost all cultures across the world. The lives saved by the proliferation of cell phone communication is phenomenal — emergency calls, quick first responders, warnings of severe weather are only a few examples.”

New Light on Brain Tumors

When patients with brain tumors undergo surgery, it’s hard for surgeons to tell where tumor ends and normal brain starts, which often means cancerous tissue is left behind. But generous margins may compromise brain function.

Now, a technique known as stimulated Raman scattering microscopy has shown better discrimination in preclinical studies, said investigators led by Sunney Xie, PhD, of Harvard University, who hope to develop the technology into a handheld probe to be used in the operating room.

Tumor tissue is relatively high in protein but low in lipids, while normal brain tissue is rich in both, the investigators noted in Science Translational Medicine. The Raman signal, generated by a laser and color-coded for tumor and normal tissue, allows doctors to tell which tissue is which — in real time during surgery.

In a blinded experiment, pathologists compared Raman images of mouse brain tissue with various stages of glioma with the same tissue stained with hematoxylin and eosin. They were able to make the correct diagnosis in all cases with the staining and in 99.5% of cases with the Raman images.

In mice with a human glioblastoma, the Raman method allowed researchers to distinguish tumor-infiltrated tissue from normal tissue, even in regions where both appeared normal under the usual bright light conditions. Hematoxylin and eosin staining later confirmed the differences.

The researchers noted that the method still needs some engineering development to make it usable in a normal operating room. A clinical trial is in planning stages.

— Michael Smith

Keeping Neurons on the Straight and Narrow

New insights into nervous system development and the body’s built-in quality control systems to forestall abnormal growth may lead to new treatments for neurodegenerative diseases, researchers at the University of California San Diego suggested.

Led by Yishi Jin, PhD, they reported identifying a two-component system in the laboratory roundworm C. elegans, involving a protein called EBAX-1 that functions as a detector of misfolded proteins in larval neurons and a heat shock protein that helps remove or repair the incorrectly developing neuronal proteins.

They also determined that this process helped protect against environmental stress such as hyperthermia, which can further impede the rapid and complex development process, with upregulation occurring when larvae were exposed to temperatures of 25 degrees C instead of the normal 20 degrees.

Because EBAX-1 is a highly conserved protein also found in humans, these findings may ultimately be helpful in developing therapies for diseases such as Alzheimer’s and Parkinson’s that are characterized by neuronal degradation, the researchers reported in Neuron.

— Nancy Walsh

Turned Off Gene Switches On Inflammation

Smooth muscle cells (SMCs) rush to the site of vascular injury and begin a cascade of pro-inflammatory responses that can lead to atherosclerosis — but the nature of the underlying biology responsible for SMCs pro-inflammatory reaction wasn’t known until now.

It appears that Kruppel-like factor (KLF) 15 — one of several of the KLF gene family members known to regulate blood vessel biology — was reduced by about seven-fold in human vessel samples that had been subjected to injury, according to Yuan Lu, MD, of Case Western Reserve University in Cleveland, and colleagues.

In addition, researchers found that KLF-15-deficient mice fed a high-fat diet had more and larger vascular lesions than controls and that KLF-15 blocked the function of a molecule called NF-kB, a dominant factor responsible for triggering inflammation — thereby finding a potential mechanism to explain KLF-15’s fundamental role in maintaining an inflammation-free state, they wrote in the Journal of Clinical Investigation.

These findings reveal more of the origins of inflammation in vascular diseases and may eventually lead to new, targeted treatment options, researchers wrote.

— Chris Kaiser

Growth Factor May Regulate Telomeres

Cortisol has garnered more attention as the hormone that could play a role in regulating telomere length, but insulin-like growth factor-1 (IGF-1) may have more of an influence, research suggests.

In a literature review, several studies showed that both IGF-1 and telomere length diminish with age, and both were positively and strongly correlated with each other, Anna Aulinas, MD, of Hospital de Sant Pau in Barcelona, and colleagues reported in Clinical Endocrinology.

“IGF-1 could be a tangible candidate involved in telomerase activation in cell growth and proliferation,” they wrote.

It’s not clear if the relationship is just an association, or if it has a cause-effect relationship, the researchers noted. But it is known that hormones play a role in regulating the function of telomerase, the enzyme charged with keeping telomeres long by preventing degradation after mitosis.