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More Confusing Data Regarding Mobile Phone Use and Brain Tumors

On May 31, 2011, the World Health Organization (WHO) through the International Agency for Research on Cancer (IARC) classified mobile phone use as Group 2B or "possibly carcinogenic." A panel of 31 experts reached this conclusion after reviewing existing data--no new research was performed. Unfortunately, the classification as "possibly carcinogenic" by the WHO is essentially meaningless and provides the public with no useful information.

The most recent scientific article to address this issue, "Mobile Phone Use and Brain Tumors in Children and Adolescents: A Multicenter Case–Control Study," was published in the Journal of the National Cancer Institute on July 27, 2011. This was a multi-center case-controlled study conducted in Denmark, Sweden, Norway and Switzerland and included all patients aged 7-19 years diagnosed with a brain tumor. 352 brain tumor patients and 646 controls were interviewed regarding cell phone usage.

The conclusion that has received widespread press is that "Our primary analysis does not point to a statistically significantly increased risk for brain tumors in children that is associated with the use of mobile phones." In other words, cell phone use does not cause brain tumors in children or adolescents.

But is that the conclusion that should really be reached from this study? Short answer: NO.

First, the methodology is the repeatedly used and notoriously flawed case-control interview. This method has a variety of sources of error and it is unclear why it continues to be used and, importantly, funded.

Second, at least some funding is provided by major telecommunication companies: TellaSonera, Erickson AB and Telenor.

Third, when actual usage and subscription data are analyzed (as opposed to subjective interview data), the authors found "a statistically significantly increased risk among users with the longest period since first subscription." In other words, the risk of developing a brain tumor increased with longer cell phone use. Oddly, this conclusion did not make the headlines.

And lastly, the question asked in this study is close to but not quite what most of us want answered: Does the use of cell phones in childhood and adolescence increase the risk of developing a brain tumor in adulthood?

So, what is the take home message? The data on cell phone use and risk of brain tumor is conflicting. At this point, the published studies have limitations ranging from methodology errors, to funding conflicts of interest.

What should you do? Use the speaker phone feature. Use text messaging (except when driving). And limit mobile phone usage in children and adolescents.

More Updates on Cell Phone Usage and and Brain Tumors

The current issue of the Journal of the American Medical Association (JAMA, February 23, 2011), details a never before studied aspect of cell phone-brain interaction. In an article entitled, "Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucose Metabolism," the authors report that cell phone usage alters brain glucose metabolism.

The study was conducted at Brookhaven National Laboratory. Forty seven healthy volunteers participated. Each person had a PET scan before and then after a 50 minute recorded conversation (with the sound muted so that auditory activation was not imaged by the PET scan). The authors found that brain regions nearest the cell phone antenna displayed significantly higher glucose metabolism after the 50 minute phone call.

The authors concluded that the finding is of unknown clinical significance.

The second update comes from the journal, Bioelectromagnetics (January 28, 2011). This study, entitled, "Time Trends (1998-2007)in Brain Cancer Incidence Rates in Relation to Mobile Phone Use in England," reviewed age group specific national cancer incidence rates in the United Kingdom. The authors found no statistically significant change in the incidence of brain cancer among men and women.

The authors conclude that despite a dramatic increase in cell phone usage between the years 1998 and 2007, there has been no particular change in the incidence of brain cancer in the United Kingdom. The authors do not recommend any intervention to limit cell phone usage at this time.

Until there is definitive data regarding the relationship between cell phone use and brain tumor formation, it is prudent to limit cell phone usage particularly among children with developing brains.

We will continue to post new information on this blog as it becomes available.

Even More on Cell Phones and Brain Tumors

This article appeared recently in the Journal of Computer Assisted Tomography. The authors conducted a review of published studies looking at long term (10 years or more) cell phone use and incidence of brain tumor. They particularly commented on two recent large studies: The Interphone Study, a multinational study, and Swedish studies lead by Dr. Hardell. The two studies have methodology issues. An important issue for the Interphone Study is that is was largely funded by mobile phone industry.

Here are some interesting comments and conclusions:

1. Long-term cell phone use can increase the likelihood of being hospitalized for migraines and vertigo by 10% to 20%
2. Cell phone storage in front pockets has been linked to poor fertility and an increased chance of miscarriage and childhood cancer.
3. Electromagnetic radiation from a cell phone can penetrate the skull and deposit energy 4 to 6 cm into the brain. This
4. long-term cell phone use can approximately double the risk of developing a glioma or an acoustic neuroma in the more exposed brain hemisphere (the side of most cell phone use)
5. A study reported an 80% increased near significant risk (93.9%) of testicular cancer when the cell phone was kept in the left pocket, then the left testicle developed cancer; and kept in the right pocket, then the right testicle developed cancer

These are precautionary tips from the authors:

"Here are some steps one can take to reduce exposure to electromagnetic energy from cell phones:

1. Limit the use of cell phones to essential calls and keep calls short. 2. Children should be allowed to use a cell phone in cases of emergency only. Because of their developing skulls, the radiation can penetrate much more deeply. 3. Wear an air tube headset (not regular wired headset). The regular wired headset has been found to intensify radiation into the ear canal. The wire not only transmits the radiation from the cell phone but also serves as an antenna, attracting EMFs from the surroundings. 4. Do not put the cell phone in a pocket or a belt while in use or while it is on. The body tissue in the lower body area has good conductivity and absorbs radiation more quickly than the head. One study shows that men who wear cell phones near their groin could have their sperm count dropped by as much as 30%. 5. If using the phone without a headset, wait for the call to connect before placing the phone next to the ear. 6. Do not use the cell phone in enclosed metal spaces such as vehicles or elevators, where devices may use more power to establish connection. 7. Do not make a call when the signal strength is 1 bar or less, which means the phone must work harder to establish a connection.

8. Use a scientifically validated EMF protection device. There are advanced technologies available nowadays that strengthen the bioenergy field and immune system against the effects of EMF. 9. Use text instead of talk.

10. Use landlines.

11. Keep cell phone off most of the time. Let people leave messages and then call them back from a landline.

12. Limit the use of cell phones in rural areas."

So, evidence is mounting that there are health concerns related to long term cell phone use. It seems prudent to limit cell phone use especially for young children.

Brain Tumor Vaccines

In the recent weeks, there has been a lot of media attention given to brain tumor vaccines. In this post, the two of the more publicized vaccines will be reviewed. First, though, a bit about the immune system and the effects of cancer.

1. Cancer and the Immune System. Our immune system recognizes cells by their surface proteins, and can distinguish between cells that are supposed to be in our body and cells that are foreign (for example, transplanted organs) or cells that are infected with a virus. When our immune system recognizes a cell as foreign or infected, it has ways to eliminate those cells. Even though cancer cells have unusual surface proteins (due to mutation, for example), the cancer cell has developed complicated methods to avoid elimination by our immune system.
2. Immunology 101. For our purposes, there are three main types of cells in the immune system: T cells, B cells, and dendritic cells. T cells can recognize foreign cells or infected cells and can actually seek them out and destroy them. B cells produce antibodies that help guard against infectious diseases. Dendritic cells are also known as antigen presenting cells and are critically important in immune recognition of foreign cells and proteins. Dendritic cells actually take up bits and pieces of proteins, shuttle them to their cell surface and present them to T and B cells. When dendritic cells present foreign proteins from either transplanted cells or virus, for example, to T or B cells, the immune response is triggered. For many reasons, this does not happen properly in people with cancer.
3. The brain tumor vaccine concept. The thinking is that the immune system can be triggered to attack a cancer cell if the dendritic cell is primed with abundant cancer cell proteins. The dendritic cell is primed by injecting various forms of cancer proteins into the patient. The patient's own dendritic cells ingest this cancer protein, present it to T and B cells which then jump into action to find the cells bearing those cancer proteins on their surface.
4. Oncophage vaccine. This vaccine is manufactured from the patient's own glioblastoma (GBM) tissue. At surgery, a portion of the tumor tissue removed is specially packaged and sent to a company called Antigenics in Massachusetts. Antigenics purifies a protein cocktail from the tumor tissue, especially containing the key protein called heat shock protein gp96. The vaccine, called Oncophage, is prepared and sent back to the treating physician. The patient receives the vaccine through an injection every week or two. Right now, the vaccine is not for general release, it still has to go through additional clinical trial evaluation. There are currently two Phase II clinical trials, both led by Neurosurgeon Andrew Parsa at the University of California in San Francisco. One trial is for patients with newly diagnosed GBM, the second is for patients with recurrent GBM.
5. EGFRvIII vaccine. EGFR stands for epidermal growth factor receptor and it is a normal cell surface protein. In about one third of patients with GBM, their tumors have a mutated form of EGFR, called variant III or vIII. EGFRvIII is turned on all the time as opposed to normal EGFR that is turned on only when a particular chemical binds to it. In patients with GBM positive for the EGFRvIII mutation, a vaccine containing a portion of the EGFRvIII protein is given through an injection. The bits of EGFRvIII protein are ingested by dendritic cells, which in turn, activate T cells so that they will seek out and destroy tumor cells with EGFRvIII on the surface. Results from a Phase II clinical trial was recently reported. The main study sites were MD Anderson in Texas and Duke University in North Carolina. The study looked at 18 patients treated with vaccine and 17 patients treated in current standard fashion. The vaccinated patients had an average overall survival of 26.0 months compared to 15.0 months for the matched control group. That is statistically significant. The vaccine is called CDX-110 (Celldex) or Rindopepimut (Pfizer). A Phase III clinical trial will be needed prior to FDA approval.
6. Conclusions. The Oncophage vaccine is made from a patient's own tumor. The EGFRvIII vaccine is "off the shelf" and will only work in those patients with an EGFRvIII positive tumor. Though the results of clinical trial for both vaccine strategies are exciting, please remember, only very small numbers of patients have been treated, and Phase III clinical trials involving many hundreds of patients at a variety of centers will be required to determine if there is, in fact, significant benefit. These types of trials can take a long time to organize and complete.
   

More on Cell Phones and Brain Tumors

Two recently published studies on the usage of cell phones and the incidence of brain tumor reached conflicting conclusions.

The first study, "Association between number of cell phone contracts and brain tumor incidence in nineteen U.S. States," authored by Steven Lehrer, Sheryl Green, and Richard G. Stock from Mount Sinai School Of Medicine, looked at the number of cell phone subscriptions and the number of brain tumors in 19 states. The authors found an independent correlation between cell phone subscriptions and brain tumor incidence and concluded, "The very linear relationship between cell phone usage and brain tumor incidence is disturbing and certainly needs further epidemiological evaluation. In the meantime, it would be prudent to limit exposure to all sources of electro-magnetic radiation."

The second study, "Brain cancer incidence trends in relation to cellular telephone use in the United States," authored by Peter D. Inskip, Robert N. Hoover, and Susan S. Devesa from the National Institutes of Health, looked at brain tumor incidence rates from 1992 to 2006. Overall, there was a slightly downward trend except for 20-29 year old females. In this group of patients, there was a statistically significant increase in frontal lobe tumors--a region of the brain not felt to be at risk from cell phone use. The authors concluded, "Overall,

these incidence data do not provide support to the view that cellular phone use causes brain cancer."

It is difficult to explain the opposing conclusions in these two studies. One issue in both studies is that if there is a causal relationship between cell phone use and brain tumors, it would take many years of cell phone use to yield a tumor. Because the remarkable increase in cell phone use is fairly recent, we may not know for another 10 or more years if there is a relationship between cell phones and brain tumors.

In the meantime, it would be reasonable to use hands free technology and limit cell phone use in children and teens.

Do cell phones cause brain tumors?

Simple answer: we still don't know.

The results from the INTERPHONE study were published in the May issue of the International Journal of Epidemiology. This is the world's largest study on cell phone use and brain tumors. The INTERPHONE study's main goal was "to determine whether mobile phone use increases the risk of brain tumors and, specifically, whether radiofrequency energy emitted by mobile phones is tumorigenic."

An additional question addressed was: "do mobile phones increase the risk of brain tumors within the first 10-15 years of use?"

Unfortunately, due to methods, biases inherent in any epidemiology study of this magnitude, changes in mobile phone usage patterns and technology, no clear conclusions can be drawn from this study.

The International Agency for Research on Cancer (IARC) sponsored this multicenter study among 13 nations.

The INTERPHONE study is a case control study. Investigators first identified cases of meningioma and glioma between 2000 and 2004. There were 2708 glioma patients and 2409 meningioma patients studied. A "matched" control patient was identified for each tumor patient. That is a patient without a brain tumor who was of the same sex, approximately the same age, and from the same geographic region. There were 2972 matched controls for the glioma group and 2662 for the meningioma group.

During face to face interviews, all participants were questioned in detail about their past cell phone use. If the patient had died or was too ill to be interviewed, a "proxy" was interviewed.

As you can see, the results are completely dependent on a person's precise recall of past cell phone use and may not be entirely accurate.

Additional data analysis is ongoing and a large, prospective study is underway. So for now, no specific guidelines can be given regarding cell phone use and brain tumor.

• However, common sense would tell us to limit a child's usage, use speaker phone and hands free methods, use text messaging (but not while driving), and don't always listen with the same ear.