Cell Phone Link to Brain Tumors -- Still No Clear Answers

Roxanne Nelson

May 18, 2010

May 18, 2010 — Does cell (mobile) phone use cause brain tumors? The results from the largest study ever designed to answer to that question have been eagerly anticipated, but it seems that the jury is still out.

The conclusions from the long-awaited INTERPHONE project, the largest study ever conducted on mobile phone use and cancer risk, are decidedly inconclusive.

Overall, the authors report that no increase in risk for glioma or meningioma was observed with the use of mobile phones. Although there were suggestions of an increased risk for glioma in people with the highest levels of exposure, they note that "biases and error limit the strength of the conclusions we can draw from these analyses and prevent a causal interpretation."

The possible effects of long-term heavy use of mobile phones require further investigation, they conclude.

An increased risk of brain cancer is not established from the data from INTERPHONE.

The study, published online May 17 in the International Journal of Epidemiology, is part of the combined analysis of the national data collected for the 13 country INTERPHONE project, coordinated by the International Agency for Research on Cancer (IARC).

"An increased risk of brain cancer is not established from the data from INTERPHONE," said Dr. Christopher Wild, PhD, director of IARC, in a statement. "However, observations at the highest level of cumulative call time and the changing patterns of mobile phone use since the period studied by INTERPHONE, particularly in young people, mean that further investigation of mobile phone use and brain cancer risk is merited."

Response From the Wireless Industry

The results of this study have been welcomed by the wireless industry. Jack Rowley, PhD, director of research and sustainability at the GSM Association, an organization of mobile operators and related companies, said that the "overall conclusion of no increased risk is in accordance with the large body of existing research and many expert reviews that consistently conclude that there is no established health risk from radio signals that comply with international safety recommendations."

In a statement, he added that "the researchers warn against focusing on the extreme values and that interpretation should be based on the overall balance of the evidence."

Michael Milligan, secretary general of the Mobile Manufacturers Forum, said that the INTERPHONE project provides significant further reassurance about the safety of mobile phones.

"The absence of increased health risks includes long-term mobile phone use for more than 10 years," he said in a release. "The authors make it clear that the data [were] insufficient for a clear interpretation of possible risk from self-reported heavy use due to a number of possible errors or biases."

For example, Mr. Milligan points out, the paper notes that there is evidence that people diagnosed with brain tumors overreported their mobile phone use, and that such recall bias might be more likely if people perceive that mobile phone use is associated with brain tumors, as has been widely speculated in the media.

However, he concurs that additional research is needed. "The mobile industry supports the need for ongoing research," he said. "In fact, a number of longer-term studies are already underway, such as the COSMOS study, which will follow the health of 250,000 European mobile users for 20 to 30 years."

Several studies, Mr. Milligan added, are now looking at children and teenagers, including the international MobiKids and CEFALO studies and the Australian MoRPhEUS project.

Flaws With INTERPHONE

Approximately 30 epidemiologic studies, along with experimental research, have attempted to evaluate the possible association between mobile phone use and the risk for brain and salivary gland tumors, but results have been inconclusive or even contradictory. Last year a report released by the International Electromagnetic Field (EMF) Collaborative concluded that studies that are independent of the telecom industry consistently show there is a "significant" risk for brain tumors from mobile phone use.

As previously reported by Medscape Oncology, the report stated that studies independent of industry funding have more consistently found higher risks for brain tumors when exposure was 10 or more years, and that even some industry-funded studies demonstrated a connection between mobile phone use and the risk for brain tumors.

The study's design results in serious underestimation of risk of brain cancer.

The EMF Collaborative was less than enthusiastic about the results from the INTERPHONE study, and in a release, stated that "the study's design results in serious underestimation of risk of brain cancer."

All INTERPHONE data collection was completed in 2004, and more than 5 year later much remains to be published; some results have not even been considered for publication, the Collaborative notes.

According to Lloyd Morgan, BSc, lead author of the EMF Collaborative's report, "the 5-year-old results are woefully inadequate as a gauge of risk today, as adults and children now speak on cell phones many hours a day, compared with only 2 to 2.5 hours a month at that time."

Another flaw in the data is that the results were only provided for gliomas and meningiomas, not tumors within the 20% of the brain's volume irradiated by mobile phones, Mr. Morgan pointed out in the rebuttal. Risk was also not broken down by sex, which may have obfuscated even higher risk for meningiomas in women.

Joel M. Moskowitz, PhD, director of the Center for Family and Community Health, School of Public Health, at the University of California, Berkeley, also found the study flawed and, rather than being inconclusive, found that it showed evidence of harm.

"The INTERPHONE study is flawed in ways that biased results against finding harmful effects," he reported in a release. "And yet, it still found harmful effects. How much larger would those effects have been or what additional harmful effects would have been identified if the study had been unbiased?"

Dr. Moskowitz points out that, despite the bias against finding tumors, the study did find a "significantly increased risk of glioma" among heavy users. "These individuals were 40% more likely to get glioma, and almost twice as likely to get glioma on the side of their head where they placed their cell phones," he said.

"Although 1640 hours of cell phone use may sound substantial, the average user in the United States today could fall into this high-risk use category after about 13 years of use," he added.

Study Details

The INTERPHONE project was initiated in 2000, following the completion of a feasibility study conducted in 1998 and 1999, which concluded that an international study of the relation between mobile phone use and brain tumor risk would be feasible and informative.

It was designed as an international set of case–control studies in 13 countries that focused on tumors located in tissues that absorb the most radiofrequency energy emitted by mobile phones: tumors of the brain (glioma and meningioma), tumors of the acoustic nerve (schwannoma), and tumors of the parotid gland.

The objective of the INTERPHONE study, led by Elisabeth Cardis, PhD, from the Centre for Research in Environmental Epidemiology in Barcelona, Spain, was to determine whether the use of mobile phones increased the risk for these tumors.

The study was conducted as an interview-based case–control study, and the main analyses, based on matched sets only, involved 2409 meningioma cases with 2662 matched controls and 2708 glioma cases with 2972 matched controls.

The majority of study participants were not heavy users. The authors report that the prevalence of regular mobile phone use 1 year before the reference date was 52% for meningioma cases (ranging from 34% to 73% across study centers) and 56% for the matched controls (35% to 78%). Prevalence was higher among glioma cases (62% overall; range, 42% to 80%) and among control subjects (64% overall, range: 45% to 84%), but this reflected the sex distribution of the tumor types.

No Evidence for Meningioma, Inconclusive for Glioma

The major findings included:

  • A reduced odds ratio (OR) related to ever having been a regular mobile phone user was seen for glioma (OR, 0.81; 95% confidence interval [CI], 0.70 - 0.94) and meningioma (OR, 0.79; 95% CI, 0.68 - 0.91).

  • An elevated OR was not observed 10 or more years after first phone use (OR for glioma, 0.98; 95% CI, 0.76 - 1.26; and OR for meningioma, 0.83; 95% CI, 0.61 - 1.14).

  • ORs were less than 1 for all deciles for lifetime number of phone calls and for 9 of the deciles for cumulative call time.

  • ORs for glioma tended to be higher among patients who reported using the phone on the same side of their head as the tumor.

  • In the 10th decile for recalled cumulative call time (1640 hours or more), the OR for glioma was 1.40 (95% CI, 1.03 - 1.89) and for meningioma was 1.15 (95% CI, 0.81 - 1.62).

The researchers conclude that for meningioma, "there is little evidence to counter a global null hypothesis," and that the study found no indication of an increased risk for meningioma in people using mobile phones.

However, for glioma, there was an increased OR in the highest decile of cumulative call time; this included people with tumors located in the temporal lobe and those who reported using their phone primarily on the same side of the head as the tumor. Still, the researchers point out, the evidence for an increased risk for glioma in the highest users was inconclusive, because the increase could be due to one or more of the possible sources of errors.

There was a participation rate of 78% among glioma cases, of 64% among meningioma cases, and of 53% among the control subjects. Although these numbers are not unusually low, the authors note, they do raise the possibility of selection bias with respect to the use of mobile phones.

The authors also note that the lower OR seen for regular mobile phone users, compared those who were never regular users, "seems unlikely to reflect a genuine protective effect and makes our results difficult to interpret."

The possible effects of long-term heavy use of mobile phones on risk of brain tumors require further investigation.

These results are consistent with most of the research that has been published to date, but "the possible effects of long-term heavy use of mobile phones on risk of brain tumors require further investigation, given increasing mobile phone use, its extension to children, and its penetration worldwide," they conclude.

Dr. Cardis, lead author of the report, pointed out that INTERPHONE will continue with additional analyses of mobile phone use and tumors of the acoustic nerve and parotid gland.

"Because of concerns about the rapid increase in mobile phone use in young people — who were not covered by INTERPHONE — [the Centre for Research in Environmental Epidemiology] is coordinating a new project, MobiKids, funded by the European Union, to investigate the risk of brain tumors from mobile phone use in childhood and adolescence," she said in a statement.

The IARC has scheduled a comprehensive review of the carcinogenic potential of mobile phone use, under the auspices of its Monographs Programme. The review is scheduled for May 24 to 31, 2011, and will consider all published epidemiologic and experimental evidence, including the new data from the INTERPHONE study.

The study was funded by the European Fifth Framework Program, "Quality of Life and Management of Living Resources'," national and local funding sources in participating countries, and the International Union Against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers' Forum and GSM Association. Provision of funds to the INTERPHONE study investigators via the UICC was governed by agreements that guaranteed INTERPHONE's complete scientific independence. Dr. Cardis has disclosed no relevant financial relationships.

Int J Epidemiol. Published online May 17, 2010.

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