Thursday, October 22, 2009

Cell Phones and Brain Cancer -- Jury Still Out

From Medscape Medical News
Roxanne Nelson

October 14, 2009 — Cellular telephones have become an integral part of everyday life; they are now used by an estimated 4 billion people worldwide. But this is a relatively new technology, and there are lingering concerns about health risks, in particular a risk for brain cancer.

A new report suggests that that regular use of cell phones can result in a "significant" risk for brain tumors. But previous studies have been inconsistent. Even so, some European countries have taken precautionary measures, aimed specifically at children.

In the United States, a recent Senate hearing examining the safety of cell phones was inconclusive, saying that although more research is needed, it might be wise to begin taking precautionary measures right now. The National Cancer Institute also said that additional research is needed.

In this special feature, Medscape Oncology presents the views of experts from both sides of the case.

The new report, "Cellphones and Brain Tumors: 15 Reasons for Concern. Science, Spin and the Truth Behind Interphone," was released in August by the International Electromagnetic Field (EMF) Collaborative, a group that includes Powerwatch and the Radiation Research Trust in the United Kingdom, and the EMR Policy Institute, ElectromagneticHealth.org, and The Peoples Initiative Foundation in the United States.

More than 40 scientists and officials from 14 countries endorsed the report, which concluded that:

Studies that are independent of the telecom industry consistently show there is a "significant" risk for brain tumors from cell phone use.

The EMF exposure limits advocated by industry and used by governments are based on a false premise that a cell phone's electromagnetic radiation has no biological effects except for heating.
The danger of brain tumors from cell phone use is highest in children, and the younger a child is when he/she starts using a cell phone, the higher the risk.
"We have had zero reaction from the industry about the paper," Lloyd Morgan, a retired electronics engineer, an active member of several international science organizations, and the report's lead author, told Medscape Oncology. "What they're doing is a nonresponse response; they haven't challenged anything in it."

This report has intensified a controversy that has been brewing for nearly 2 decades and still remains largely unresolved. Approximately 30 epidemiologic studies have attempted to evaluate a possible association between cell phone use and the risk for brain and salivary gland tumors. There have also been a number of experimental studies involving cell cultures and animal models.

Results, however, have been inconclusive or even contradictory. But studies independent of industry funding have more consistently found higher risks for brain tumors when exposure was 10 or more years, explained Mr. Morgan, adding that "even some industry-funded studies show that there is a connection between cell phone use and the risk of brain tumors."

Interphone Results Flawed

The issue of cell phone safety was to have been settled once and for all by the huge 13-nation industry-funded Interphone study, which was begun nearly 10 years ago. Even though data collection was completed in 2004, the results have still not been published. The European Parliament has called the delay "deplorable," and has demanded an explanation for it. Although the combined results have not yet been released, 14 Interphone studies (11 single country and 3 multicountry studies) with partial results have been published.

"Results of Interphone have been delayed by about 4 years," said Elizabeth Barris, founder of the nonprofit People's Initiative Foundation and coauthor of the new report, in an interview. "It was supposed to be released this September. We wanted to make sure that our report was released before Interphone. We wanted to bring attention to the issue, including the fact that Interphone has been delayed for so long."

With only 4 exceptions, the industry-funded Interphone studies found no increased risk for brain tumors from cell phone use, explained Mr. Morgan. In contrast, a series of Swedish studies, led by Lennart Hardell, MD, PhD, from the Department of Oncology, Orebro Medical Center, in Sweden, which were independent of industry funding, reported numerous findings of significantly increased brain tumor risk from cell phone and cordless phone use.

As you review these studies, you begin to get strong evidence of extremely improbable results.
An analysis of the results from the Interphone studies suggests that the use of a cell phone actually protects the user from a brain tumor, or that the studies had serious design flaws. "In any one study, you can see this incredibly skewing toward protection," said Mr. Morgan. "As you review these studies, you begin to get strong evidence of extremely improbable results."

In fact, Mr. Morgan and his coauthors identified 11 flaws in the Interphone studies: selection bias, insufficient latency time, definition of "regular" cell phone use, exclusion of young adults and children, no investigation of brain tumor risk from cell phones radiating higher power levels in rural areas, exclusion of exposure to other transmitting sources, exclusion of some brain tumor types, exclusion of tumors outside the cell phone radiation plume, exclusion of brain tumor cases because of death or illness, recall accuracy of cell phone use, and funding bias.

"Almost all flaws caused an underestimation of risk," he said, "and for exposure under 10 years, they found protection for cell phones."

The Cellular Telecommunications Industry Association (CTIA), the wireless association's industry trade group, has not specifically responded to the new report, according to Mr. Morgan. However, John Walls, vice president of public affairs at CTIA, told Medscape Oncology that "since we are not a scientific organization, with respect to the matter of health effects associated with wireless base stations and the use of wireless devices, CTIA and the wireless industry have always been guided by science and the views of impartial health organizations."

Peer-reviewed scientific evidence has overwhelmingly indicated that wireless devices do not pose a public health risk, Mr. Walls said. "In addition, there is no known mechanism for microwave energy within the limits established by the [Federal Communications Commission] to cause any adverse health effects," he said. "That is why the leading global heath organizations, such as the American Cancer Society, the National Cancer Institute, the World Health Organization, and the US Food and Drug Administration, all have concurred that wireless devices are not a public health risk."

Initial Red Flags

In the United States, the possible connection between tumors and cell phone use became highly publicized in 1993, when Florida resident David Reynard appeared on the popular television show Larry King Live and blamed cell phones for causing his wife's lethal brain tumor. Mr. Reynard filed a lawsuit against the manufacturer; he ultimately lost the case, but dozens of other lawsuits followed in its wake, along with numerous scientific studies that attempted to find or disprove a link. Most of the lawsuits have been dismissed, and thus far, none have gone to trial.

But the subject was picked up by the media, and scientists and experts argued publicly on opposing sides of the issue. Reports in the popular media prompted Congressional hearings on the safety of cell phone use, and during those sessions, it became clear that cell phones had not been tested for "safety prior to going into commerce," said George Carlo, PhD, MS, JD, during a 2008 radio interview with CFRO, a co-op radio station based in Vancouver, British Columbia. "Because the food and drug industry had not required that testing, Congress asked the industry to fill in those data gaps."

The industry invested $28.5 million and launched the first telecommunications industry-backed studies to investigate possible health risks stemming from cell phone use. Dr. Carlo, who is a Fellow of the American College of Epidemiology and has served on the faculty of several medical schools, headed the Wireless Technology Research program, which ran from 1993 to 1999. It was the largest program in the world to look at the potential dangers of cell phone use and electromagnetic radiation.

"In the middle of 1998, we began to have some of our long-term studies completed and it became clear that we were seeing things that no one expected," said Dr. Carlo. "We found that cell phone radiation caused leakage in the blood–brain barrier, it caused genetic damage in the form of disruption of normal DNA repair, and it caused more than a doubling of the risk of rare neuroepithelial tumors."

"After 6 years," he continued, "we found that cell radiation caused an increased risk of acoustic neuromas."

During the time these Wireless Technology Research studies were being carried out, the use of cell phones mushroomed. In 1993, there were 15 million cell phone users in North America; by 1999, there were more than 100 million.

"We went back to the industry and suggested that they issue warnings, but they promptly said no," Dr. Carlo said in the interview. "Those of us running the research program knew we had an ethical responsibility to go public with those findings, and we did go public, independent of the industry and independent of the government agencies that were overseeing the work."

In 2001, Dr. Carlo coauthored a book entitled Cell Phones. Invisible Hazards in the Wireless Age: An Insider's Alarming Discoveries, which discussed the findings.

I don't think they ever really expected to find that cell phones were dangerous.
Dr. Carlo felt that part of the reason for the refusal to issue warnings was that the telecommunications industry was not prepared for the results of the research. "I don't think they ever really expected to find that cell phones were dangerous, and when we presented our findings, they were ill prepared for them. They also didn't want to compromise their industry."

As for the lack of action on the part of government regulatory agencies, Dr. Carlo pointed out that agencies in the United States and Canada did not require any premarket testing of cell phones. "The only legal jurisdiction step that they had available in 1999 was to ban cell phones. And from a political point of view, banning cell phones would not be an easy thing to do, especially since our findings were the first ones of their type," he said.

These were "red flags of risk"; there weren't enough data at the time to actually prove that the risk was real, Dr. Carlo emphasized. "That is not the case now; there has been confirmatory evidence. But in 1999, regulatory agencies did not have the scientific evidence to be able to sustain the types of legal challenges that would have come from the industry had they tried to ban cell phones."

Trail of Research

Much of the more recent research on the safety of cell phones has not specifically found a health risk; however, researchers have pointed out the limitations of their studies and left the door open. Part of the problem in assessing the potential connection between brain tumors and cell phone use is the relatively short period of time that the devices have been heavily in use in a large population and the long latency period for many tumors.

A National Cancer Institute study published in 2001, for example, did not support the hypothesis that the use of cell phones caused brain tumors, but the researchers noted that a limitation of their work was that they did not assess risks after a potential induction period of more than several years or among people with very high levels of daily or cumulative use (N Engl J Med. 2001;344:79-86).

A 2009 review from researchers at the Karolinska Institutet in Stockholm, Sweden, reported that studies published to date do not demonstrate an increased risk after approximately 10 years of use for any brain tumor or other head tumor (Epidemiology. 2009;20:639-652). Thus far, data do not suggest a causal association between cell phone use and fast-growing tumors, but they note that for slow-growing tumors, such as meningioma and acoustic neuroma, "the absence of association reported thus far is less conclusive because the observation period has been too short."

Another recent review, the third in a series of updates to an original report issued by the Royal Society of Canada, concluded that although there is no clear evidence of adverse health effects associated with radiofrequency fields during the period from 2004 to 2007, continued research is recommended to address specific areas of concern, including the use of cell phones by children (J Toxicol Environ Health B Crit Rev. 2009;12:250-288).

The Interphone studies to date have largely reported negative results, finding no association between tumors and cell phone use. One study did not find a link between an increased risk for malignant or benign parotid gland tumors and exposure to radiofrequency electromagnetic fields, but the authors concluded that cell phones "have not been used long enough to exclude their possible carcinogenic effect after long-term use, and more epidemiologic studies including long-term users are clearly warranted" (Am J Epidemiol. 2006;164:637-643).

However, the results of an Israeli Interphone study suggest a positive association between cell phone use and the development of parotid gland tumors (Am J Epidemiol. 2008;167:457-467). The authors noted that this was a single study, and therefore did not provide enough evidence to assume causality. They recommend additional investigations of this association, with longer latency periods and large numbers of heavy users, to confirm the findings. "Until more evidence becomes available, we believe that the precautionary approach currently adopted by most scientific committees and applied by many governments should continue to be used," they wrote.

Some of the strongest evidence supporting a link between brain tumors and cell phone use comes from a series of Swedish studies, led by Dr. Hardell. Overall, the reserachers found that risk increased with the number of cumulative hours of use, higher radiated power, and length of cell phone use. They also reported that younger users had a higher risk. In fact, the highest risk was among people who were younger than 20 years at the time of first use (Int J Oncol. 2006;28:509-518; Int Arch Occup Environ Health. 2006;79:630-639; Arch Environ Health. 2004;59:132-137; Pathophysiology. 2009;16:113-122).

A meta-analysis that incorporated 11 long-term epidemiologic studies in this field also reported a link between cell phone use and brain tumors. Using a cell phone for 10 years or longer was positively associated with the development of an ipsilateral brain tumor; in fact, it doubled the risk (Surg Neurol. 2009;72:205-214).

Melange of Reactions

As in the literature, there is no consensus among physicians and scientists about the severity of risk, or even if it exists. On its Web site, the National Cancer Institute notes that although a consistent link has not been demonstrated between cell phone use and cancer, "scientists feel that additional research is needed before firm conclusions can be drawn." Likewise, the American Cancer Society points out that although the weight of the evidence has shown no association between cell phone use and brain cancer, information on the potential health effects of very long-term use, or use in children, is not available.

Sam Milham, Jr. MD, MPH, former chronic disease epidemiologist at the Washington State Department of Health and clinical associate professor at the University of Washington School of Public Health in Seattle, has published several critiques on cell phones and health risks. "I personally think there is a real risk, and have felt this way even before the studies were published, based on animal work," he told Medscape Oncology.

Dr. Milham contends that all of the negative studies have been seriously flawed. "The fact that same-sided tumors with long latency are showing increased risks is bad news, since brain tumors have very long latencies," he said. "The same-sided risks are very important since dose is important. The most worrisome fact is the number of people who are being exposed."

Putting a cell phone against your head is like putting one side of your head against a microwave oven.
"Putting a cell phone against your head is like putting one side of your head against a microwave oven," he added.

Last year, Ronald B. Herberman, MD, director of the University of Pittsburgh Cancer Institute and UPMC Cancer Centers in Pennsylvania, sent a memo to faculty and staff advising them to limit cell phone use based on his interpretation of recent research. In 2008, he testified before a Congressional Subcommittee on the subject of tumors and cell phones, and urged more independent and definitive research.

However, many experts are not convinced that there is a link. Currently, there is no evidence that cell phones cause brain cancer, said John Moulder, PhD, professor and director of radiation biology at the Medical College of Wisconsin in Milwaukee.

"The published data have rather consistently shown the absence of evidence for a human health hazard," he told Medscape Oncology. "Conclusive cancer epidemiology requires long follow-up time and accurate exposure assessment. The exposure assessment in this field has been very weak, as it depends on peoples' memories of how they were using mobile phones 10 or more years ago."

He emphasized that the studies based on what side of the head people used their phones are particularly weak, since most people use them on both sides, at least some of the time.

"Until we can find a way to measure actual exposure over long periods of time, the epidemiology will never be conclusive," he added.

Dr. Moulder pointed out a number of flaws in the new report. "The authors seem to have combed the literature for reports that support their concerns, and have ignored everything that would contradict their views," he said. "A scientific risk assessment needs to looks at all the evidence."

Although the report states that cell phone radiation has been shown to cause the blood–brain barrier to leak, Dr. Moulder noted that only 1 group has found that effect. "Other groups have been unable to replicate the effect."

Part of the problem with this research is that it is nearly impossible to prove that something doesn't cause cancer. "The closest you can come is to repeatedly try to show that it does and repeatedly fail," he said.

The Road Ahead

On the heels of the release of the new cell phone report, a Senate hearing on the health effects of cell phone use was held in September, and chaired by Sen. Tom Harkin (D-Iowa). The take-away message from expert testimony was that more and better research is needed to determine if there is a risk to human health. And nearly all of the researchers and scientists who spoke at the hearing advocated a precautionary approach in the meantime.

We just don't know what the answer is.
"We just don't know what the answer is," said Sen. Arlen Specter (D-Pennsylvania) during the hearing. "Precautions are not a bad idea. They may not be a good idea, but they are not a bad idea. And the issue of children is something we should look at a little more closely."

Several countries, including Israel, France, and Finland, and the United Kingdom have decided not to wait for additional data; instead, they have issued warnings about the use of cell phones and advise taking precautionary measures, especially for children. New legislation in France, for example, will ban advertising of cell phones that is directed to children younger than 12 years of age and the sale of cell phones designed for children younger than 6 years. In addition, France will introduce new limits for radiation from the phones and require cell phones to be sold with earphones.

Realistically, it is going to be difficult to change behaviors now that cell phones are so entrenched in daily use, explained Mr. Morgan. "In some parts of the world, it is nearly impossible to get a land-line telephone, so cell phones are the only option."

Cell phones can be made safer, and the technology to do so exists right now. For example, said Mr. Morgan, "you can get a 10,000-fold reduction in exposure simply by keeping the phone 6 inches away from the head."

There are also steps that can be taken right now to make cell phones safer to use, he said. These include using a wired headset (not a wireless headset such as a Bluetooth), using speaker-phone mode, or sending text messages; keeping the phone away from the body when not in use; avoiding use in a moving car, train, or bus, or in rural areas at some distance from a cell tower, because any of these uses will increase the power of the cell phone's radiation; and keeping the cell phone turned off until you need to use it.

The authors also recommend using a corded land-line phone whenever possible, instead of a wireless phone, and to avoid cell phones when inside buildings, particularly with steel structures. Since children face a greater health risk, they should not be allowed to sleep with a cell phone under their pillows or at the bedside, said Mr. Morgan. Ideally, those younger than 18 years should not use a cell phone at all, except for emergencies.

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