The FDA received numerous media inquires about a recently published paper (Pooled analysis of two case–control studies on use of cellular and cordless telephones and the risk for malignant brain tumors diagnosed in 1997–2003by Hardell et al.) reporting increased risk of malignant brain tumor associated with long term use ( >10 years) of cell phones and cordless phones. This is not a new study but is an analysis of two studies previously published in 2003 and 2005. Both studies were population based case control studies. Cases were recruited based on histopathological diagnoses submitted to regional cancer registries in Uppsala/Örebro and Linköping regions of Sweden. Control subjects were taken from a population registry covering the whole population in Sweden.

Several studies have been recently published on the risk of long term cell phone use (> 10 years) and brain cancer1. The results reported by Hardell et al. are not in agreement with results obtained in other long term studies. Also, the use of mailed questionnaire for exposure assessment and lack of adjustments for possible confounding factors makes the Hardell et al. study design significantly different from other studies. These facts along with the lack of an established mechanism of action and absence of supporting animal data make it difficult to interpret Hardell et al. findings.

The FDA continues to monitor studies looking at possible health effects resulting from exposure to radio frequency energy. In 1999, FDA signed a Cooperative Research and Development Agreement (CRADA) with the Cellular Telecommunication & Internet Association (CTIA)2. As called for by this CRADA , FDA plans to convene a meeting in the near future to evaluate all completed, ongoing and planned research looking at health effects associated with the use of wireless communication devices and identify knowledge gaps that may warrant additional research.

Research Cooperation with the Cellular Telecommunications and Internet Association (CTIA)

FDA and the Cellular Telecommunications and Internet Association (CTIA) have a formal Cooperative Research and Development Agreement (CRADA) to do research on wireless phone safety. FDA provides the scientific oversight, obtaining input from experts in government, industry, and academic organizations. CTIA-funded research is conducted through contracts to independent investigators. The initial research will include both laboratory studies and studies of wireless phone users. The CRADA will also include a broad assessment of additional research needs in the context of the latest research developments around the world.

General Information About the CRADA

FDA Recommendations Concerning Research to be Conducted Under the CRADA

FDA has recommended CTIA fund research to address questions raised by previous studies on the effect of radio frequency exposure on micronucleus formation. The specific questions of interest to FDA are:

  • Is the reported effect of RF exposure on lymphocytes accurate and reproducible?
  • What is the role of temperature change in the observed results with RF exposure?
  • Do In Vivo RF exposures increase micronucleous formation?

CTIA followed FDA’s recommendation and funded two In Vitro studies and one In Vivo study:

  • Integrated Laboratory Systems, Research Triangle Park, NC. (In Vitro).
  • Interuniversity Center on Interaction Between Electromagnetic Fields and Biosystems, Naples and Rome, Italy. (In Vitro).
  • The Fraunhofer Institute of Toxicology and Aerosol Research, Hannover, Germany. (In Vivo).

The studies funded by CTIA satisfactorily address the research needs identified by FDA. FDA continues to monitor the progress of these studies through a regular series of progress reports and site visits.

Micronucleus Formation

  • Federal Register Notice for a Meeting (August, 2000) Text
  • Meeting Transcript, Day One WORD or PDF (note: file is 229 pages/339KB)
  • Meeting Transcript, Day Two WORD or PDF (note: file is 99 pages/148KB)
  • FDA Research Recommendations Text

Epidemiology (Studies of Human Populations)

  • Federal Register Notice for a Meeting (April, 2001) Text
  • Meeting Transcript, Day One WORD or PDF (note: file is 297 pages/357KB)
  • Meeting Transcript, Day Two WORD or PDF (note: file is 87 pages/131KB)
  • Federal Register Notice for a Meeting (May, 2001) Text
  • Meeting Transcript, Day One WORD or PDF (note: file is 599 pages/577KB)
  • Meeting Transcript, Day Two WORD or PDF (note: file is 281 pages/285KB)
  • FDA Research Recommendations WORD, PDF or Text
Results of the Danish brain tumour component of INTERPHONE Study
 

 

The first results of analyses of risk of brain tumour in relation to use of mobile telephones in the Danish part of INTERPHONE were published on 12 April 2005 in Neurology http://www.neurology.org/: Collatz Christensen H., Schüz J, Kosteljanetz M, Skovgaard Poulsen H, Boice JD, McLaughlin JK and Johansen C. Cellular telephones and risk for brain tumors: a population-based, incident case-control study. Neurology 64: 1189-1195. The study included 252 incident glioma cases, 175 incident meningioma cases and 822 randomly selected population based controls stratified on age and gender. The cases were aged 20 to 69 and diagnosed in 2000-2002 in the whole of Denmark. Participation rates were 71% for glioma, 74% for meningioma and 64% for controls. Regular mobile phone use did not increase the risk of low-grade glioma or of meningioma (low-grade glioma OR=1.08, 95% CI 0.58-2.00; meningioma: OR 1.00, 95% CI 0.54-0.1.28). No association was found with time since first exposure (only 6 meningioma and 6 low-grade glioma cases had started using mobile phones 10 years or more before diagnosis, however) or with numbers of call or hours of calls.

A statistically significant reduction in risk was seen for high-grade glioma (OR 0.58, 95%CI 0.37-0.90). The finding is puzzling as there is, a priori, no biological mechanism for such a reduction. It is noted that 18% of the glioma cases could not be interviewed as they had either died or were too ill. Although no information is provided about the grade of the tumours among non-respondents, it is likely that a large proportion of these were high-grade gliomas. In addition, patients with high-grade glioma had significantly lower scores on the Mini-Mental State Examination than patients with lower-grade glioma or meningioma. The reduced risk for high-grade glioma may therefore reflect selection and/or recall bias.

To date, few studies have included sufficient numbers of cases among long-term users to allow a definitive conclusion about a possible association between mobile telephone use and the risk of brain cancer. These results therefore need to be confirmed in other studies before firm conclusions can be drawn.

Results of other national components of the INTERPHONE Study should be published later in 2005 and 2006 (The results of the Swedish brain tumour study were published earlier this year http://aje.oupjournals.org/cgi/content/full/161/6/526/). Results from the International analyses, which will cover about 2800 glioma cases and 2400 meningioma cases and sizable numbers of long-term users, are expected later in 2005.

More information about the Danish study and its results can be found on the site of the Danish Cancer Centre www.cancer.dk.

Results from the Swedish brain tumour component of INTERPHONE Study
 

 

The first results of analyses of risk of brain tumour in relation to use of mobile telephones in the Swedish part of INTERPHONE were published on 4 March 2005 in the American Journal of Epidemiology http://aje.oupjournals.org/ : Lönn, Stefan; Ahlbom, Anders; Hall, Per; Feychting, Maria and the Swedish Interphone Study Group; Long-Term Mobile Phone Use and Brain Tumor Risk. Am J Epidemiol 161: 1-10.The study included 371 incident glioma cases, 273 incident meningioma cases and 674 randomly selected population based controls stratified on age, gender and residential area. The cases were aged 20 to 60 and diagnosed in 2000-2002 in parts of Sweden. Regular mobile phone use did not increase the risk of glioma or of meningioma (glioma OR=0.8, 95% CI 0.6-1.0; meningioma: OR 0.7, 95% CI 0.5-0.9). Similar results were found for more than 10 years’ duration of mobile phone use. No statistically significantly increased risk was seen for ipsilateral tumours or for tumours located in the temporal and parietal lobes of the brain (the areas thought to be most exposed to radiofrequency radiation emitted by mobile phones). The authors conclude that the data do not support the hypothesis that mobile phone use is related to the risk of glioma or of meningioma.

Results combined analyses of acoustic neurinoma risk in the Northern European centres included in INTERPHONE
 

 

The results of combined analyses of risk of acoustic neurinoma in relation to use of mobile telephones in the Northern European countries included in the INTERPHONE Study were published online on 30 August 2005 in the British Journal of Cancer
http://www.nature.com/bjc/journal/vaop/ncurrent/index.html:
Schoemaker MJ, Swerdlow AJ, Ahlbom A, Auvinen A, Blaasaas KG, Cardis E, Collatz Christensen H, Feychting M, Hepworth SJ, Johansen C, Klæboe L, Lonn S, McKinney PA, Muir K, Raitanen J, Salminen T, Thomsen J, Tynes T. Mobile phone use and risk of acoustic neuroma: results of the Interphone case-control study in five North European countries. British Journal of Cancer – on-line 30 August 2005.

The analyses included 678 acoustic neurinoma cases and 3,553 randomly selected population based controls stratified on age, gender and residential area from Denmark, Finland, Norway, Sweden and the UK. The subjects included in the previously published Danish and Swedish analyses (Christensen et al, 2004 and Lönn et al, 2005) were included in these analyses.

Regular mobile phone use did not increase the risk of neurinoma in this pooled data set (OR=0.9, 95% CI 0.7-1.1). There was no association of risk with duration of use, lifetime cumulative hours of use or number of calls, for phone use overall or for analogue or digital phones separately. Risk of a tumour on the same side of the head as reported phone use was raised for use for 10 years or longer (OR=1.8, 95% CI: 1.1–3.1). The authors conclude that there is no substantial risk of this tumour in the first 10 years after starting mobile phone use. However, an increased risk after longer term use could not be ruled out.

Acoustic neurinoma are rare tumours, occurring in less than one adult per 100 000 per year. They are slowly growing benign tumours that generally have a good prognosis, as they only rarely undergo malignant change.

To date, few studies have included sufficient numbers of cases among long-term users to allow a definitive conclusion about the existence or not of a possible association between mobile telephone use and the risk of brain cancer. This paper presents the results of analyses based on the largest number of acoustic neurinomas to date, from European countries where mobile phones were introduced particularly early. The study included 47 cases who had started mobile phone use 10 years or more in the past.

Results of other national components of the INTERPHONE Study should be published later in 2005 and 2006. The first paper from the international analyses, which will cover about 1100 neurinoma cases and sizable numbers of long-term users, should be published shortly.

More information about the analyses can be found on the site of the Institute for Cancer Research, which coordinated these analyses: www.icr.ac.uk

References cited

Collatz Christensen, Helle; Schüz, Joachiml; Kosteljanetz, Michael; Skovgaard Poulsen, Hans; Thomsen Jens and Johansen, Christoffer. Cellular Telephone Use and Risk of Acoustic Neuroma, Am. J. Epidemiol. 2004 159: 277-283

Lönn, Stefan; Ahlbom, Anders; Hall, Per; Feychting, Maria. Mobile Phone Use and the Risk of Acoustic Neuroma. Epidemiology 2005 15 (6): 653-659.


 

Results from the UK brain tumour (glioma) component of the INTERPHONE Study
The first results of analyses of risk of brain tumour in relation to use of mobile telephones in the British part of INTERPHONE were published on 19 January 2006 in the British Medical Journal http://bmj.bmjjournals.com/onlinefirst_date.shtml: Hepworth J, Schoemaker MJ, Muir KR, Swerdlow AJ, van Tongeren MJA, McKinney PA. Mobile phone use and risk of glioma in adults: case-control study. BMJ Online First bmj.comThe study included 966 incident glioma cases and 1716 randomly selected population based controls stratified on age, gender and residential area. The cases were aged 20 to 60 and diagnosed in 2000-2004 in five areas of the UK. Regular mobile phone use did not increase the risk of glioma (OR 0.94, 95% CI 0.78 to 1.13). There was no relation for risk of glioma and time since first use, lifetime years of use, and cumulative number of calls and hours of use. A significant excess risk was found for reported phone use ipsilateral to the tumour (OR 1.24, 95% CI 1.02 to 1.52); however, a significant reduction in risk was seen (OR 0.75, 95% CI 0.61 to 0.93) for contralateral use: recall bias was postulated, as the explanation for this finding.

 

 

Results from the German brain tumour (glioma and meningioma) component of the INTERPHONE Study
The first results of analyses of risk of brain tumour in relation to use of mobile telephones in the German part of INTERPHONE were published in the advance online access edition of the American Journal of Epidemiology, 27 January 2006
http://aje.oxfordjournals.org/papbyrecent.dtl: Joachim Schüz, Eva Böhler, Gabriele Berg, Brigitte Schlehofer, Iris Hettinger, Klaus Schlaefer, Jürgen Wahrendorf, Katharina Kunna-Grass, and Maria Blettner. Cellular Phones, Cordless Phones, and the Risks of Glioma and Meningioma (Interphone Study Group, Germany).

The authors conclude that, consistent with results of most published studies, overall use of mobile phones is not associated with an increased risk of brain tumour. However, the elevated risk of glioma in long-term users needs to be confirmed in further studies.

To date, few studies have included sufficient numbers of cases among long-term users to allow a definitive conclusion about the existence or not of a possible association between mobile telephone use and the risk of brain cancer. The German study included only 12 cases of glioma who had used phones for 10 years or more. Results of further studies are needed before firm conclusions can be drawn.

The first paper from the combined analyses from 13 INTERPHONE countries, which will cover about 2800 glioma and 2400 meningioma cases and sizable numbers of long-term users, should be published in 2006.

 

 

 

The study included 366 incident glioma cases, 381 meningioma cases, and 1494 randomly selected population based controls matched on gender, age, and study centre. The cases were aged 30 to 69 and diagnosed between 2000 and 2003 in three areas of Germany (Mainz, Bielefeld and Heidelberg). Overall, regular mobile phone use did not increase the risk of glioma (OR 0.98, 95% CI 0.74 to 1.29) or meningioma (OR 0.84, 95% CI 0.62 to 1.13). Amongst persons who had used a mobile phone for at least ten years, however, the relative risk increased to 2.20 (95% CI 0.94 to 5.11) for glioma, while no increase was observed for meningioma. There was no difference between users and non-users in risk of either glioma or meningioma in the lobe of the brain thought to receive the highest exposure to radiofrequency radiation from mobile phones (the temporal lobe).

 

 

The authors conclude that, consistent with results of most published studies, use of a mobile phone, either in the short or medium term, is not associated with an increased risk of glioma.

To date, few studies have included sufficient numbers of cases among long-term users to allow a definitive conclusion about the existence or not of a possible association between mobile telephone use and the risk of brain cancer. This is the largest study of brain cancer in relation to mobile telephones to date, with 66 cases who had started use 10 years or more previously. Results of further studies are needed before firm conclusions can be drawn.

Results of other national components of the INTERPHONE Study should be published later in 2006. The first paper from the international analyses, which will cover about 2800 glioma cases and sizable numbers of long-term users, should be published in 2006.

 

To date, few studies have included sufficient numbers of cases among long-term users to allow a definitive conclusion about the existence or not of a possible association between mobile telephone use and the risk of brain cancer. This is one of only two studies available at present with sizable numbers of subjects who used mobile phones for 10 years or more. Results of further studies are needed before firm conclusions can be drawn.

Results of other national components of the INTERPHONE Study should be published later in 2005 and 2006. The first paper from the international analyses, which will cover about 2800 glioma cases and 2400 meningioma cases and sizable numbers of long-term users, should be published in 2005.

More information about the Swedish study group can be found on the site of the Karolinska Institute.
http://www.imm.ki.se/divisions/epidemiology/index.html
The article is part of a thesis and a press release in English is available at:

http://www.imm.ki.se/PDF/Press/Press%20release%20nov%2025%202004.pdf

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