Use of mobile phones and risk of brain tumours: update of Danish cohort study

BMJ 2011; 343 doi: http://dx.doi.org/10.1136/bmj.d6387 (Published 20 October 2011)
Cite this as: BMJ 2011;343:d6387

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Displaying 1-10 out of 12 published

I am concerned about the validity of the reported outcomes of the
Danish Cohort Study on the relationship of cell phones to cancer that
was published in the British Medical Journal this year. I know your
journal is highly respected worldwide and that people expect utmost
care is taken by peer reviewers and editors in deciding what
constitutes a well-designed and executed study, and what study
conclusions reasonably follow. I believe on both counts the Danish
Cohort Study fails and that this study should be retracted from BMJ.

The study, with a cohort of over 723,000 people, concludes that there
is no causal link between brain cancer and cell phone radiation, as
it is reported in your Journal. This conclusion has been highly
publicized.

It is, however, highly questionable.

Since cell phone radiation is the "agent " being studied, in order to
determine whether there is a link between exposure and cases, one
would assume the study clearly delineated significantly-to-heavily
exposed people from light-to-non-exposed people. But that is not
the case.

Only length of cell phone subscription was considered. Length of
subscription? Certainly you, as I, have known people who have
maintained a cell phone, but only use it for emergencies. Back when
cell phone minutes were quite expensive (which was during the period
studied, 1982 to 1995), there would have been all the more reason to
be spare in use. But these people, if they owned a cell phone, were
put into the same "exposed" pool with those who used it heavily! How
does that tell us anything useful about the exposure link to cancer?

And who would have been the heaviest users in those times ? Most
likely, those who depended on using the cell phone for their jobs,
and whose cell phone minutes were being paid for by the corporations
they worked for. Does that not make sense? Wouldn't you want to
know what happened to those heavily exposed users? And yet, over
200,000 of these very people were excluded from the study because
they did not have individual subscriptions. They, ironically, became
misclassified as "unexposed".

You must agree that these practices contaminate the groups, and thus,
call the conclusions into serious question. Research Design 101---
this is basic.

And what about people who started using cell phones in 1996--the year
after the subscription cut-off date? They could have used the cell
phone for eleven years, been diagnosed with cancer in 2007 (the last
year for monitoring outcomes), and yet been considered "unexposed."

The amount of confounding is very surprising for a study published in
BMJ. The implications for continuing to lend this study validity by
not retracting it, could be very serious for the Journal, and even
more importantly, for the people who rely on the educated judgment
and expertise of its editors and reviewers when making decisions for
their family, or their nation. What you do makes a difference.

I call upon you to retract the Danish Cohort Study, and to do so in a
way that informs the public of the change.

Sincerely,

Margaret Meade Glaser

Competing interests: None declared

Margaret Meade Glaser

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This study has several design flaws that should prevent the authors from any conclusions concerning the impact of mobile phone use on the development of brain cancer. These flaws are as follows:

1. Exposure data
The only information about the person’s exposure to mobile phone radiation is the length of the mobile phone subscription with the mobile phone operator. Such exposure information is irrelevant because it leads to the following: two persons, one of which spends many hours per week on the phone and the other who spends just a few minutes per week are in this study analyzed as if belonging to the same exposure group when they own the subscription of the mobile phone for the same length of time. It means that the highly exposed persons and the nearly unexposed persons are mixed up in the same exposure group. Analysis of such data can not provide valid information about correlation of the exposure to mobile phone radiation and induction of brain cancer.

2. Composition of the control group
From the starting cohort of 723 421 mobile phone subscribers were excluded all corporate subscribers (200 507 subscribers). Therefore, the people who most likely were the heaviest users and were the most exposed to mobile phone radiation were excluded from the study. Besides this, the exclusion of the corporate subscribers has likely led to “contamination” of the control group. As the authors state in the discussion section: “…Because we excluded corporate subscriptions, mobile phone users who do not have a subscription in their own name will have been misclassified as unexposed…”. This means that some of the possibly highly exposed corporate users, who did not have personal phone subscriptions, have ended up as non-exposed persons in the control group.
Because of the cut-off time of the exposure to mobile phone radiation set for year 1995 but the analysis of the cancer induction was done based on the 2007 cancer registry data, any person who got subscription after the cut-off year of the study was considered as non-exposed by the set-up of the study. It means that for example a person diagnosed in 2007 with brain cancer, who had subscription of the mobile phone from year 1996 was, by the design of the study, considered as a non-exposed person who got brain cancer. Whereas, in reality, this was a person who was exposed for 11 years and who got brain cancer.

Finally, even though the study started with over 723 421 mobile phone subscribers, and after some exclusions used 358 043 subscribers, the statistical evaluations presented in tables 1, 2 and 3 in the article are largely based on just a few, or few tens, of cases. What it means is that the statistical results are unreliable because of low numbers.

The all above mentioned flaws and shortcomings make this study unreliable and make impossible to draw any valid conclusions. The conclusions presented by the authors are not supported by the presented data.

Competing interests: None declared

Dariusz Leszczynski, Research Professor

STUK - Radiation and Nuclear Safety Authority, Laippatie 4, FIN-00880 Helsinki, Finland

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We have been asked by the BMJ editors to write a reply to the two responses by Khurana and Philips to our recently published article of the Danish cohort study (1).

Khurana (2) raises questions in regard to the number of brain tumour cases in the cohort, the exposure assessment method, and the cohort ascertainment.

In relation to the number of brain tumour cases in the long-term subscribers (10-fold compared to the previous update), this effect is a mixture of the aging of the cohort (with the brain tumour incidence increasing by age (3)) and that subscribers starting in 1994 and 1995, which constitute the majority of subscribers (4), moved from the category of 5-9 years of exposure to 10+ years of exposure. Thus, the number of person-years in the group of subscribers with 10+ years of exposure increased remarkably, as stated in the paper (from 170’000 to 1.2 million person-years) (1). Time trends of glioma and meningioma in the Nordic countries including Denmark are reported in a paper that will be published very soon (5).

In relation to exposure, the only historical data available were the subscriptions. Individual data on use would have been a great advantage, but we do not see how individual level "extrapolation" would be possible. As described in the discussion section of the paper (1), we have indications from a validation study with participants of the Danish Interphone study that subscription holders were four times more likely to report regular mobile phone use before 1996 compared with the general Danish population (6). In addition, we had information on the average use of mobile phones for subscribers in Denmark (also stated in the discussion section of the paper (1)), and there were indications that subscribers in the early years were in fact on average heavier users than subscribers in the later years.

With regard to ascertainment, children are not included in the subscriber cohort, as subscriptions are not in their name. For this reason the relationship between mobile phone use and risk of brain tumours in children was investigated with a different design, published in 2011 (7). Corporate subscriptions that did not allow the allocation of the phone to an individual could not be regarded in the cohort, the effect of this misclassification and its impact on risk estimation has been described in length in previous publications of the cohort (6,8). The expected dilution would not allow the detection of a small risk increase, as the one observed in Interphone (9) restricted to the 5-6% of heaviest users of mobile phones in the population, but is incompatible with the assumption that the risk in Interphone is a gross underestimate (as suggested in Appendix 2 of (9)) or with the risk increases observed in the case-control studies by Hardell (10).

Philip and Lamburn are also concerned about the composition of the cohort (11). Their comparison of the present study to the two follow ups (6, 12) however is not appropriate; the current update is based on a linkage of the subscriber cohort and a nationwide cohort on social inequality in cancer, therefore the overall study population is smaller than the whole Danish population, as described in the methods of our paper (1). The reason was that to obtain information on the highest attained education and income for each individual, for adjustment of the risk estimates. Subjects for which these data were not available were therefore not part of the new update, for example persons born outside Denmark or persons born before 1925. With respect to other RF exposure sources, the percentage of the contribution of the sources mentioned by Philip and Lamburn (11) refer to exposure from far-field sources (the contribution of personal mobile phone use is excluded) and do not reflect exposure to the head (13).

(1) Frei P, Poulsen AH, Johansen C, Olsen JH, Steding-Jessen M, Schüz J. Use of mobile phones and risk of brain tumours: update of Danish cohort study. BMJ 2011;343:d6387.

(2) Rapid response by Khurana VG. Danish cohort study: Questions regarding selection, exposure, and tumour incidence. http://www.bmj.com/content/343/bmj.d6387?tab=responses

(3) Schmidt LS, Nielsen H, Schmiedel S, Johansen C. Social inequality and incidence of and survival from tumours of the central nervous system in a population-based study in Denmark, 1994–2003. Eur J Cancer 2008;44: 2050-7.

(4) Schüz J, Waldemar G, Olsen JH, Johansen C. Risks for central nervous system diseases among mobile phone subscribers: a Danish retrospective cohort study. PLoS One 2009;4:e4389.

(5) Deltour I, Auvinen A, Feychting M, Johansen C, Klaebo L, Sankila R, Schüz J. Mobile-Phone Use and Incidence of Glioma in the Nordic Countries 1979-2008: Consistency Check. Epidemiology, in press.

(6) Schüz J, Jacobsen R, Olsen JH, Boice JD Jr, McLaughlin JK, Johansen C. Cellular telephone use and cancer risk: update of a nationwide Danish cohort. J Natl Cancer Inst 2006;98:1707-13.

(7) Aydin D, Feychting M, Schüz J, Tynes T, Andersen TV, Schmidt LS, et al. Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study. J Natl Cancer Inst 2011;103(16):1264-76.

(8) Schüz J, Johansen C. A comparison of self-reported cellular telephone use with subscriber data: agreement between the two methods and implications for risk estimation. Bioelectromagnetics 2007;28:130-6.

(9) INTERPHONE Study Group. Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study. Int J Epidemiol 2010;39:675-94.

(10) Hardell L, Carlberg M, Hansson MK. Mobile phone use and the risk for malignant brain tumors: a case-control study on deceased cases and controls. Neuroepidemiology 2010;35:109-14.

(11) Rapid response by Philips AM and Lamburn G. Updated study contains poor science and should be disregarded. http://www.bmj.com/content/343/bmj.d6387?tab=responses

(12) Johansen C, Boice J Jr, McLaughlin J, Olsen J. Cellular telephones and cancer—a nationwide cohort study in Denmark. J Natl Cancer Inst 2001;93:203-7.

(13) Frei P, Mohler E, Neubauer G, Theis G, Bürgi A, Fröhlich J, et al. Temporal and spatial variability of personal exposure to radio frequency electromagnetic fields. Environ Res 2009;109:779–85.

Competing interests: None declared

Patrizia Frei

Aslak H Poulsen, Christoffer Johansen, Jørgen H Olsen, Marianne Steding-Jessen, Joachim Schüz

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Allan H. Frey, Scientist (allan@freys.us)

Randomline Inc, Potomac, MD USA

Recently, policy makers, journalists and the Public have been inundated with conflicting information and confusion concerning the biological effects and safety of cell phone radiation.

For some years now epidemiology studies have been done, supposedly to determine if present and future cell phones are safe. But there is a fatal assumption in all these epidemiology studies, whatever their outcome, which render them of little value for such a purpose. The microwave wavelength and modulation (pattern of the energy) radiated by present and future phones are generally different from the radiation characteristics of past phones, which are the primary subject of the epidemiology studies. The experimental biology research that has been published shows that wavelength and modulation does matter. For example, published experiments show that the well known microwave hearing phenomena (often cited as the Frey effect) will occur at specific wavelengths and modulations and not others. The same holds for other published microwave biological effects, such as heart function and brain function effects, as would be expected in biology. Thus, the radiation from cell phones of yesteryear that is the subject of the epidemiology studies, including this one, does not have the same biological effects as the radiation from current and expected future phones (1).

In addition, there are other faults in the epidemiology studies which invalidate them. For example, most of the patients and most of the data analyses in two of the prominent epidemiology studies are irrelevant to the issue of whether handheld cellular telephones cause brain cancer. Most of the patients (86%) in one study used car telephones or bag telephones, not handheld telephones; the antennae used with car and bag telephones are well away from the head, so there is little, if any, exposure of the head to the energy (2). Most of the patients (82%) in another of the studies had no or negligible use of a handheld telephone (3). Shortly after these papers were published, another epidemiology study was published in another prominent medical journal. The authors lumped together in their analyses car, bag, and handheld telephones as though the use of all these types of telephones gave the same head exposure as handheld telephones (4). And the currently reported update of that study has the same faults (1). Thus, most of the analyses in these epidemiology studies actually show that if you have no exposure you have no effect; they are irrelevant to the issue.

A further source of confusion is that the microwave biology literature is unusual in that the military office that controlled most of the US funding for biological research in this area had blatant conflicts of interest. Prof. Nicholas Steneck, who at the time was director of the Collegiate Institute for Values and Science at the University of Michigan, received a major grant from the National Science Foundation's Program for Ethics and Values in Science and Technology. He and Institute fellows in biology and physics used it to do an in-depth case study of this area of research. They documented how the conflicts of interest derailed the science in this area, blocked promising lines of research, led to confusion and to the insertion of gross misinformation into the scientific literature and resulted in the virtual extinction of research on the biological effects of low intensity microwave radiation, such as used by cell phones, in the USA. Prof. Steneck details this in a book he wrote and also in a book that he edited: in a chapter by Frey and another chapter by Medici (5, 6).

There are also various implicit assumptions that have crippled the research and led to misinformation in the epidemiology reports. For example, this area of biological research, like some others, is encumbered with a vocal few who imagine that they are the possessors of "real truth." They like to talk about the dogma, such as the "laws of physics." For them, if the data do not conform to the dogma, then the data must be wrong. But one does not challenge data with the current dogma. That's upside down; the essence of science is that it's the dogma that is tested by data. Or these naysayers say, as in a recent cell phone epidemiology paper, that they don't know of an explanation for how the radiation can affect an organism and they imply that, thus, there cannot be an effect. But biologists cannot yet explain most biological effects. For example, people used aspirin for one hundred years before biology advanced enough to recently provide an explanation for its effects. And, contrary to what the naysayers say, there are in fact numerous published experimental papers showing how the radiation affects living organisms (7).

Further, it is to be expected that concepts conceived at one level of observation will have to be modified as observational ability improves. In 1840, it took more than six months to go from Washington DC to San Francisco by mule and wagon. No one then could even imagine, much less believe, that today I could have breakfast in Washington and lunch in San Francisco, as I have sometimes done.

The Public has not been well served by these epidemiology studies.

1. Frei P, Poulsen A, Johansen C, Olsen J, Steding-Jessen M, Sch?z J. Use of mobile phones and risk of brain tumours: update of Danish cohort study. BMJ 2011 343:d6387doi:10.1136/bmj.d6387

2. Muscat J, Malkin M, Thompson S, Shore R, Stellman S, McRee D, Neugut A, Wynder E. Handheld cellular telephone use and risk of brain cancer. JAMA 284:3001-3007 (2000).

3. Inskip PD, Tarone RE, Hatch EE, Wilcosky TC, Shapiro WR, Selker RG, Fine HA, Black PM, Loeffler JS, Linet MS. Cellular-telephone use and brain tumors. N Engl J Med 344(2):79-86 (2001).

4. Johansen C, Boice J Jr, McLaughlin J, Olsen J. Cellular telephones and cancer-a nationwide cohort study in Denmark. J Natl Cancer Inst 93:203 -207 (2001).

5. Steneck NH. The Microwave Debate. Cambridge, MA:The MIT Press, 1984.

6. Steneck NH ed. Risk/Benefit Analysis: The Microwave Case. San Francisco, CA:San Francisco Press, 1982.

7. Frey AH ed. On the nature of electromagnetic field interactions with biological systems. R. G. Landes Co., Austin, 1994

Competing interests: None declared

Allan H. Frey, scientist

Randomline Inc

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2 November 2011

Dear Sir/Madam

I would be very interested to know how this study got past the editorial and peer-review processes at the BMJ.

Is it possible to post the peer-reviewers' comments on the BMJ website?

Competing interests: None declared

Sarah J Wright, scientist

Wired Child

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Either being a male cellphone subscribers were significantly protected from all cancers or this study has such fundamental flaws that it becomes nonsensical. Immediately in Table 1, the very first result found a statistically significant protection from all cancers, OR=0.96, 95% CI=0.95-0.85. The calculated p-value for this finding is 1.5*10-7, equivalent to one chance in 6.6 million that was a random result.

When the authors state, "there was no increased risks of tumours of the central nervous system," it was technically correct but only by removing important from the statement. Placed in context this statement might have been, "While there was no increased risk of tumours of the central nervous system, there was significant protection from all cancers in men.

Other Rapid Responses have addressed why any risk of central nervous tumours would be highly unlike to be found because of other fundamental flaws.

Competing interests: None declared

L Lloyd Morgan, Sr. Research Fellow

Environmental Health Trust

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(BMJ. 2011 Oct 19;343:d6387 Frei et al studied tumours in the central nervous system among Danish mobile phone subscribers aged ?30 born in Denmark after 1925, subdivided into subscribers and non-subscribers of mobile phones before 1995, which included 358?403 subscription holders with 3.8 million person years and excluded business users. The authors acknowledge some design limitations and concluded that there were no increased risks of tumors of the central nervous system, associated with duration of mobile phone subscription.

We note a number of additional serious errors, faulty study design and major contradictions that bias the analysis toward Type II errors (falsely negative results) as detailed below.

1. In view of the study aim to investigate how mobile phone use impacts risk of brain tumours, the size of the cohort was too small to find a significant change in underlying risk of relatively rare brain tumours, and accordingly lacked statistical power.

More specifically: The background rate of brain cancer in the general population is about 7 per 100,000 persons and the rate of benign brain tumors is about 12 per 100,000. Therefore, studying brain tumors in a prospective cohort of less than several million persons has a very low chance of finding any increase of a risk.

  • The authors note that study had no information on actual cellphone use, nor on side of the head commonly used, but only on subscriptions that began in 1995 or earlier. These parameters are among the least reliable ones to estimate exposure and find an effect.
  • As others have noted in rapid response here, subscribers who began to use phones after 1995 and those who were business users before 1995 - are considered nonsubscribers, (since no data were available on subscriptions after 1995). This effectively puts those who began to use phones later than 1995 into the nonuser (control) group, although we all know that pricing, etc. stimulated both wider use and longer call times (exposures) among these later users who were also more socially diverse.

    2. The authors lacked information about other sources of microwave radiation (cordless phones, routers, and base stations). Because "user" was defined as someone who made one call a week for six months, this combines slight and heavy users into one group. This could lead to a serious, systematic underestimation of the relationship between actual phone exposure and brain tumors risk.

    3. From the onset: The cohort is too small, the average exposure time is too short, and the design is therefore likely to find no effect.

    Brain tumors are known to have a latency of at least ten years (or more) in adults. Thus, the time period observed here, together with the relatively small size of the cohort monitored, at the outset was unlikely to find any effect attributable to cellphone use.

    Regarding latency covered in studies of brain tumours and mobile phone radiation, a recent comment from respected epidemiologists, Rudolf Saracci and Jonathan Samet, notes, that none of the today's established carcinogens, including tobacco, could have been firmly identified as increasing risk in the first 10 years or so since first exposures began. Ionizing radiation is a recognized cause of brain tumours. With the exceptions of rare instances where exposure began in childhood or was very high, radiation induced cases occur on average after 10-20 years since the time of first exposure.

    The INTERPHONE study shares with all studies previously carried out on mobile phones and cancer the inherent limitation that it can investigate only a short period of observation since first exposure; the distribution of exposure is brief and truncated, leaving limited exposure time for an exposure-related cancer to develop.

    4. The study confuses "statistical significance" with "public health importance".

    In studies of rare events, it is difficult to have sufficient numbers to produce statistically significant results within the conventional 95 % confidence interval, where the chance that the finding is wrong is .05 or less. In fact, this study actually finds increased risks in several subgroups, but fails to report these effects because the numbers do not achieve statistical significance (as to be expected in underpowered studies). These borderline significant results are consistent with other reports from well-designed case control studies that have found significant risks of glioma after a decade of regular use.

    A weight of the evidence approach that examines the totality of studies on this topic finds that most well-designed cohort studies have found a doubled risk, according to a recent meta-analysis that differentiated quality of studies (5). Thus, the lack of statistical significance in this study reflects the lack of statistical power. Lack of an association in an underpowered study never can be: proof of no association between cellphone use and brain cancer.

    5. Significant data are "diluted" and obscured among other findings.

    For example: the authors report that "The highest estimate was found for cerebral ventricle based on eight cases (2.58 (1.08-6,15) . And even though this result achieves statistical significance, it is dismissed.

    6. Contrary to Frei et al's assertion that there is no secular increase in brain tumour incidence, incidence has increased significantly in some Nordic countries that have been heavy and persistent mobile phone users, while Swedish incidence data are underreported.

    The study claims that there is no underlying secular trend in brain tumors in Sweden and therefore cellphone use does not cause brain cancer. Comparisons of tumours reported to the Swedish National Board of Health with those reported to the cancer registry indicate that brain tumour incidence is significantly under-reported as is incidence of soft tissue tumours, leukemia and lymphoma. (6) In other Nordic countries, there is clear evidence of recently increased incidence in brain tumours with reduced mortality. From 2005-09, brain tumour incidence annually increased in Norway in males and females 1.7% and 2.8 % iand .5 % and .1 % annually in Finland. Mortality declined substantially during this same time period in Norway -.8% and -1.7% in males and females in Norway and -11.4% and -.5% in Finland. (see appendix below).

    7. Unacknowledged conflict of interest

    The authors declare no conflict of interest in support for this analysis. In fact, the original cohort was first established partly with Danish phone company funding.

    (accessed 12/30/09)According to Bloomberg Financial News (Mobile Phones Don't Cause Brain Cancer of Leukemia, Study Finds; 2/26/02), the International Institute for Epidemiology completed a study that cost $373,000 and was funded in part by Denmark's largest phone company, Tele Danmark A/S, which is partially owned by SBC Communications, and the second-largest mobile phone service in Denmark, Sonofon A/S, owned by Telenor AS and BellSouth Corp.

    Based on the evolving science at hand, in May of this year the IARC expert committee (2) determined that cellphones and other wireless radiation should be classified as possible carcinogens. In reaching that conclusion, IARC expressly rejected earlier reports from the same Danish cohort used by Frei et al, noting a number of methodological flaws in the original design which also afflict this updated analysis. Reflecting the emerging evidence, a growing number of the world's leading experts are issuing calls for protective policies.

    Two leaders of the World Health Organization Interphone study Elisabeth Cardis, PhD, of Barcelona's Centre for Research in Environmental Epidemiology and Siegal Sadetzki, M.D., M.P.H., of Tel Aviv's Gertner Institute for Epidemiology and Health Policy , advise the following (7):

    " While more studies are needed to confirm or refute these results, indications of an increased risk (of brain cancer) in high and long -term users from interphone and other studies are of concern... even a small risk at the individual level could eventually result in a considerable number of tumors and become an important public-health issue. Simple and low cost measures, such as the use of text messages, hands free kits, and/or the loudspeaker mode of the phone could substantially reduce exposure to the brain from mobile phones. Therefore, until definitive scientific answers are available, the adoption of such precautions, particularly among young people, is advisable."

    We concur.

    Selected References

    1. Schuz J, et al. (2006) Cellular telephone use and cancer risk: update of a nationwide Danish cohort. JNCI 2006. 98:1707-13.

    2. WHO IARC Monograph Working Group, Carcinogenicity of radiofrequency electromagnetic fields. Lancet Oncol. 2011 Jul;12(7):624-6.

    3. Frei P, et al, (2010) Classification of personal exposure to radio frequency electromagnetic fields (RF-EMF) for epidemiological research: Evaluation of different exposure assessment methods., Environ Int 2010 Oct;36(7):714-20

    4. Gandhi O, et al (2011) Exposure Limits: the underestimation of absorbed cellphone radiation, especially in children Electromag Biol & Med. Early Online: 1-18.2011.

    5. Levis et al (2011) Mobile phones and head tumours. The discrepancies in cause-effect relationships in the epidemiological studies--how do they arise? Env Helth, 2011, 10:59

    6. Barlow et al (1998) The completeness of the Swedish Cancer Register

    Acta Oncologica, 2009; 48: 27_33

    7. Cardis E and Sadetzki S, Indicationsn of Possible Brain-Tumour Risk in Mobile-Phone Studies: Should we be Concerned? Occup Environ Med 2011;68:169-171 doi:10.1136/oem.2010.061358

    APPENDIX:

    INCREASED AGE-ADJUSTED INCIDENCE IN BRAIN TUMOURS

    MALES AND FEMALES IN FINLAND AND NORWAY

    Finnish National Cancer Registry, as reported in NORDCAN, Association of the Nordic Cancer Registries ? All Rights Reserved. 27.10.2011

    Finland: Brain Tumour Incidence

    Finland: Mortality

    Norway: Brain Tumour Incidence

    Norway: Mortality

Competing interests: None declared

Devra L Davis, Director

Ronald B. Herberman, Yael Stein

Environmental Health Trust

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The study by Frei et al provides evidence that overall risk of cerebral malignancies is no higher in mobile phone users than those who do not use mobile phones. Two important confounding factors need to be considered. Firstly, data on mobile phone usage is limited to duration of subscription. This does not differentiate between "heavy" users who may spend several hours on the phone each day and "light" users who make very few calls. Secondly, it does not differentiate between the different devices/manufacturers of each phone. Design differences between manufacturers may influence risk. The authors' conclusions should therefore be interpreted with these confounders in mind.

Competing interests: None declared

Dorothy M Gujral, Clinical Research Fellow

Royal Marsden Hospital

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Re: Use of mobile phones and risk of brain tumours: update of Danish cohort study. Frei, et al. 343:doi:10.1136/bmj.d6387

In their introduction, Frei et al. [1] state: "So far, the mechanism of potential non-thermal interaction between radio frequency electromagnetic fields (EMFs) and living systems is unknown." This statement does not concur with scientific knowledge.

Mobile phones typically have three types of EMF emissions associated with them: in the GSM system a 900 MHz radio frequency, a 217 Hz pulsing signal and an extremely low frequency magnetic field (ELF MF) associated with the battery [2]. The ELF component has so far been ignored in all epidemiological studies of mobile phone exposure and cancer. During phone use, this ELF component exposures the whole brain to MFs ranging from a few to tens of micro-tesla, above the intensity of power frequency ELF-MFs that have been repeatedly associated with increased risk of brain tumours in adults [3,4].

Animals across a wide range of species detect small changes in the Earth's magnetic field, which is exploited for navigation. Homing pigeons and newts are estimated to have a limiting magnetic detection sensitivity of 0.01 micro-tesla and magnetic compass sensitivity below 0.2 degrees [5]. Two types of magneto-receptor are widely discussed [6, 7], one based on structures of magnetite particles, the other on a chemical compass exploiting the radical pair mechanism, RPM in which low intensity MFs alter the quantum spin state of the unpaired electrons in a free radical pair. Both mechanisms are relevant to the interaction of mobile phone EMFs in humans.

Thus, the human brain contains magnetite particles [8], some up to 600 nm in size, capable at body temperature of transducing both low intensity ELF MFs and microwave EMFs [9, 10].

The RPM forms part of basic spin chemistry [11] in which low intensity MFs can increase the lifetime of free radical pairs by singlet- to-triplet, S-T, interconversion of their quantum spin states. The increased lifetime of free radicals allows increased availability to cause biological damage, for example to DNA. The energy levels involved are some ten million times below thermal energy, the action being of the nature of a quantum mechanical switch.

There is compelling evidence that the avian magnetic compass utilises the RPM acting in the eye on cryptochromes protein molecules [12], best known for their function in controlling circadian rhythms. The magnetic compass can be disrupted by radio frequency fields. In the American cockroach disruption was seen by 1.2 MHz fields at 0.018 micro-telsa [13], well below current ICNIRP public exposure guidelines [14]. There is evidence that human cryptochromes are magneto-sensitive [15] and that ELF MFs disrupt circadian rhythms in man [16].

IARC has recently classifieds radio frequency EMFs as a 2B possible carcinogen, based on the main body of case-control epidemiology and accumulated exposure to mobile phone radiation and increased risk of brain tumours in heavy users [17]. Research into the possible health effects of mobile phones should now concentrate on designing epidemiological studies with more relevant exposure metrics and at investigating further the mechanistic pathways by which exposure may increase the risk of brain tumours and other adverse health outcomes. Meanwhile, precaution against undue exposure is warranted and should be encouraged.

References:

1. Frei P, Poulsen AH, Olsen JH, Schuz J. 2011 Use of mobile phones and risk of brain tumours:update of Danish cohort study. BMJ 2011;343:d6387 doi: 10.1136/bmj.d6387

2. Tuor M, Ebert S, Schuderer J, Kuster N. Assessment of ELF Exposure from GSM Handsets and Development of an Optimized RF/ELF Exposure Setup for Studies of Human Volunteers. Foundation for Research on Information Technologies in Society, Report: BAG Reg. No. 2.23.02.-18/02.001778, Zurich, January 2005.

3. O'Carroll MJ, Henshaw DL. 2008. Aggregating epidemiological evidence: comparing two seminal EMF reviews. Risk Anal 28:225-234.

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Competing interests: None declared

Denis L Henshaw, Emeritus Professor of Human Radiation Effects

School of Chemistry University of Bristol Cantocks Close, Bristol, BS8 1TS

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This update has failed to control for a number of flaws and omissions that severely detracted from the quality of data in the previous paper, published in 2006 [1].

The first flaw in the paper is the ability to correctly identify the mobile phone subscribers between 1987 and 1995. 620,602 early subscribers were validated in their original data set. 200,507 were corporate users whose names were unknown and were excluded, leaving 420,095 'early users'. This update has excluded another 61,692 of the 'early users' resulting in a participation rate of only 58% of identified early subscribers. All of the remaining 42% will be placed in the "non-user" category (the majority of which, by the author's own admissions, will be likely to be the heaviest user group in the data set).

Even for the remaining 58% of identified subscribers, no information was collected pertaining to actual mobile phone usage, using "number of subscription years" as a surrogate. Not only does the paper contain no data on mobile phone subscribers since 1995, it has absolutely no information about actual exposure - despite frequently using the term 'exposure' in the paper. In the 2011 update on the carcinogenicity of radiofrequency electromagnetic fields, the 30 scientist IARC monograph panel were quite critical of the failings in the original paper: "In this study, reliance on subscription to a mobile phone provider, as a surrogate for mobile phone use, could have resulted in considerable misclassification in exposure assessment." [2]

An even more damaging limitation is the exposure classification in the "non-subscriber" part of the cohort, which has been analysed as if it is a group of individuals with no mobile phone exposure. On top of containing the 42% from the originally identified dataset, the proportion of the Danish population that held a mobile phone subscription increased from 10% to 95% between 1995 and 2004. This not only means that a significant majority of the non-subscriber category will be mobile phone users, but many of whom will have used their phone for over 10 years, despite being classified in the study as "non-users". The magnitute of this confounder makes meaningful comparisons in the data impossible.

Finally, the authors made no effort to control for any other forms of RF exposure. The primary author (Frei) has previously demonstrated that about only about 30% of adult microwave exposure now comes from their mobile phone handset use [3], with approximately 30% from cordless phones, 30% base stations and 10% other sources. These other exposures could be highly relevant, as Lennart Hardell has repeatedly shown increases in brain tumours associated with extensive cordless phone use [4], a technology that has been in widespread use since 1995.

It is unclear how this latest paper makes any novel contributions to the existing literature on mobile phones and brain tumours, as it contains significantly worse flaws than either the INTERPHONE group's research or the papers published by Lennart Hardell. The magnitude of the limitations in this research make meaningful analyses and conclusions virtually impossible.

It is also unclear how this study is meant to help doctors and other health professionals make better decisions that will improve outcomes for patients as stated in BMJ's publication mission statement [5].

Sincerely
Alasdair Philips and Graham Lamburn

1. Schuz J, et al. (2006) Cellular telephone use and cancer risk: update of a nationwide Danish cohort. JNCI 2006. 98:1707-13.

2. WHO IARC Monograph Working Group, Carcinogenicity of radiofrequency electromagnetic fields. Lancet Oncol. 2011 Jul;12(7):624-6.

3. Frei P, et al, (2010) Classification of personal exposure to radio frequency electromagnetic fields (RF-EMF) for epidemiological research: Evaluation of different exposure assessment methods., Environ Int 2010 Oct;36(7):714-20

4. Hardell L, Carlberg M, Hansson Mild K. (2011) Pooled analysis of case-control studies on malignant brain tumours and the use of mobile and cordless phones including living and deceased subjects. Int J Oncol. 2011 May;38(5):1465-74. doi: 10.3892/ijo.2011.947. Epub 2011 Feb 17.

5. BMJ website. What does the BMJ publish?



Competing interests: We are both involved in running Powerwatch, a small UK NGO active in the field of EMF exposure and health since 1987. We currently advise a precautionary approach to mobile phone use, especially by children.

Alasdair M Philips, Engineer and scientist

Graham Lamburn

Powerwatch (UK NGO)

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