Remember The Criticisms of this Study When it is Later “Updated” for the Media Again

The following is criticism by independent experts on the recent Danish study “Use of mobile phones and risk of brain tumours: update of Danish cohort study,” published in the British Medical Journal, which incorrectly claims to have found no link between cell phone use and tumors.

Joel Moskowitz, Ph.D.
Berkeley, CA
Reply to the NYT article by Tara Parker-Pope  “No Cellphone-Cancer Link in Large Study”

This is a poor excuse for a cohort study. In our review of the literature on mobile phone use and tumor risk published in the Journal of Clinical Oncology in 2009, we dismissed the results of this study due to its numerous shortcomings. The current paper which includes more followup data on a smaller sample has more problems than the earlier paper. The study mis-classifies cell phone subscribers and non-subscribers which attenuates the association between subcribership and cancer risk. Moreover, the study did not assess the amount or type (e.g. hands-free use) of cell phone use or control for potential risk (e.g., cordless phone use) or protective factors (e.g., allergies).

In our review of the research, we found that the higher quality case-control studies displayed a significant association between mobile phone use and brain tumor risk, especially on the side of the head where the phone was used, after 10 years of phone use, and among heavier users.

Of great concern to many public health and medical researchers is the fact that there is little data available on the long-term effects of cell phone use among children. A recent paper shows that children’s brains absorb about twice the radiation as adults’ brains.

A dozen nations and the European Union have issued precautionary warnings about the need to reduce cell phone radiation exposure. Recommendations often include hands-free use among adults and limited use among children.

For more information about our research see a recent Q&A I did with Dr. David Katz for the Huffington Post: http://www.huffingtonpost.com/david-katz-md/cell-phone-health-risks_b_86….

Devra L. Davis, PhD, MPH
Cancer Epidemiologist and President of Environmental Health Trust

Unsurprising, biased and misleading.

From the way it was set up originally, this deeply flawed study was designed to fail to find an increased risk of brain tumors tied with cellphone use.   In order for any study of a relatively rare disease like brain tumors to find a change in risk, millions must be followed for decades.  By extending an earlier analysis on the same group of cellphone users this new report provides unsurprising, biased and misleading conclusions. It uses no direct information on cell phone use, fails to consider recent and rapidly changing nature of and exposure to microwave radiation from cellphones, cordless phones and other growing sources, and excludes those who would have been the heaviest users—namely more than 300,000 business people in the 1990s who are known to have used phones four times as much as those in this study.

Statistical significance tests are tools used in science to help understand the chance that a finding is real.  In fact,  the article reports a significant increased risk of a very rare form of glioma of the cerebral ventricle based on eight cases (2.58, 1.08-6. 1) but the authors chose to make no mention of this significant finding.  In this instance despite the small number the finding is significant.

Statistical analyses provide tools, but do not provide rules, for interpreting evidence. This means that findings can be important even when they do not reach significance statistically.   In this report, the authors reject all other findings of borderline significance completely.  In  a study of relatively rare diseases such as brain tumor, the failure to obtain statistical significance should not be confused with a lack of public health importance.  In fact, most of the reported numbers of brain tumors in this article give estimated risks where the result goes from below 1 ( a negative result meaning no increased risk), to above 1 (a positive result indicating in some instances a doubled or greater risk).

All of the few well-designed case-control studies of this issue have found significantly increased risk. Thus, these borderline findings of increased risk may well signal an important association.”

Mona Nilsson
Investigative Journalist

The writer of the editorial commentary “Mobile telephones and brain tumours”, Ahlbom from Sweden’s Karolinska Institute has come under increased scrutiny himself for conflicts of interest. Mona Nilsson has documented a number of these conflicts. Ahlbom recently lost significant credibility when he was dismissed from the WHO’s IARC Expert Panel in May.  Nilsson reported that he had failed to disclose links to the telecom industry.

Ahlbom has been a member of the Board of his brother’s telecom consulting company, Gunnar Ahlbom AB. He also did not declare his industry affiliation to the Swedish Radiation Protection Authority, where he resigned after this disclosure.  Ahlbom is a member of the International Commission on Nonionizing Radiation Protection (ICNRIP), an industry loyal organisation, and participated in setting the ICNIRP radiation exposure limits in 1998.  These standards assume that the only biological impact of microwave radiation from cellphones is heat and fail utterly to take into effect non-thermal biological effects thereby greatly underestimating risk.

Nilsson says the authors also claim that almost 90% of the Swedish population had been using mobile phones for at least 7 years by 2009.

However typical usage was very low in 2002 because of relatively high prices per minute, compared to today as shown in a graph from the Swedish Post and Telecommunications Authority. The red curve is Millions of mobile phone minutes.

Alasdair Philips, B.Sc.(Eng), DAgE, Powerwatch UK
Member of the UK Department of Health Stakeholder Group on ELF EMFs and the U.K. Health Protection Agency’s EMF Discussion Group

Of the study’s design,

This study only looks at 7% of the Danish population who had a personal cellphone subscription for at least one year during the period 1987 to 1995. It ignores corporate subscribers (the heaviest users then) and the researchers have no data at all on cellphone use since 1995 so the extra 86% of the population who started to use a cellphone since 1996 were left in the “non subscriber part of the population. This study uses seriously flawed data to make a flawed analysis and should be condemned as misleading spin.

Donald Maisch, PhD,
EMFacts Consultancy
Australia

If anything, this paper is evidence that the peer review process that this paper went through is inadequate. How could the glaring error of excluding corporate subscribers from the analysis be overlooked and the fact that all new subscribers post 1995 were relegated to being considered as non-users. As the old saying goes, “rubbish in rubbish out.”

Denis L Henshaw, PhD,
Emeritus Professor of Human Radiation Effects
University of Bristol in U.K.

This seriously flawed study misleads the public and decision makers about the safety of mobile phone use. I consider that their claims are worthless.

Dariusz Leszczynski PhD
STUK-Radiation and Nuclear Safety Authority, Finland
On his blog Between a Rock and a Hard Place

Now, let’s look at another of the largest studies, the recent update of the Danish Cohort. It is the largest study because the authors started with the population of 723 421 subscription records in Denmark for years of 1982 – 1995. However, their information on exposure of people to mobile phone radiation is even worse than in INTERPHONE. Just as reminder, in INTERPHONE people were asked how much they used phone over the period of up to 10 years, what introduced enormous bias – who remembers how much was talking on the phone not 10 years ago but just a few weeks ago. So, the exposure information in INTERPHONE was, in practice, not reliable if not outright scientifically non-existent.

The Danish Cohort is even worse. The only information that the scientists had was how long a person owned mobile phone subscription with a provider. There was no any estimation of exposure, even as poor as the recollection from memory in INTERPHONE. Such way of gathering ‘exposure data’ in Danish Cohort lead to paradoxes.

In Danish Cohort, 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 analyzed as belonging to the same exposure group when they own the subscription for the same length of time. It means that highly exposed and nearly unexposed persons are mixed up in the same exposure group. Such “data” can certainly not provide any scientifically valid information.

Even though the Danish Cohort study started with over 700 000 mobile phone subscribers, and after some exclusions (about this below) used only 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 worthless because of too low numbers. In practice the tables 1, 2 and 3 are non-informative at all.

Already the two above examples of shortcomings should be enough to preclude publication of Danish Cohort study. However, there is more. There is a big and an unforgivable error in the study design. Such error, that university students should study it as an example how not to do research.  Namely:

From the starting cohort of 723 421 mobile phone subscribers were excluded all corporate subscribers (200 507 subscribers) because the information about them was a “corporate secret”. So, the people who most likely were the heaviest users were excluded from the study. In years 1982 – 1995 using mobile phone was expensive for private persons. But this did not apply to business people and they, due to their professional needs, used extensively mobile phones.  So, the most exposed group was excluded. But hold on, this is an error but it is not the unforgivable error in study design that I mentioned above. It is this, and I quote the fragment of discussion of the Danish Cohort study:

“…Because we excluded corporate subscriptions, mobile phone users who do not have a subscription in their own name will have been misclassified as unexposed…”

It means that some of the highly exposed corporate users who did not have personal phone subscriptions (nobody knows how many)  have ended up as non exposed controls.

Let me give an example how grave this error is:

If a scientist would perform experiments on cells in laboratory and before measuring results would take some of his most exposed cells and mixed them with the unexposed cells and used such mixed sample as control sample, such activity would be condemned and such study would never be published and scientist would have a lot of explaining to do.

The same ‘thing’ has been done, by design, in the Danish Cohort study. It is unbelievable how this study passed through peer-review of appointed reviewers and journal editors.

But, hold on, this is not yet all what is wrong with the control sample in Danish Cohort study. Any person who got subscription after the cut off year of the study (1995) was unexposed by the ‘standards’ of the study. What it means? For example:

Person who was diagnosed in 2007 with brain cancer who had subscription of the phone from 1996 was by the design of the Danish Cohort study an unexposed person who got cancer. Whereas, in reality, this was a person exposed for 11 years who got cancer.

The control sample of Danish Cohort study is an unbelievable rubbish! Pardon my expression but nothing better comes to mind. The authors simply cannot know what it contains. It is a mix of unexposed and exposed persons.

The Danish Cohort study should never been published, and since it was those responsible for publication should explain themselves and the study should be immediately withdrawn, with apologies.

But the reality is (still) different. The ‘botched’ Danish Cohort study, in spite of numerous criticisms published by the same journal as rapid responses, is still a ‘valid’ peer-reviewed article. It seems as if epidemiology would have own set of scientific rules…

But, in real world, it is not uncommon that flawed studies are retracted by either journal editors or the authors themselves. A most extreme case has happened just this September, when journal editor took blame and responsibility for publication of flawed study and resigned from his Editor-in-Chief position.

So, what is our problem with mobile phone radiation and brain cancer? What is confusing and messing up and preventing future research by draining funds and providing worthless results?

It’s the epidemiology, stupid!

Devra L. Davis, PhD, MPH
Cancer Epidemiologist and President of Environmental Health Trust
Letter to the Editor of the British Medical Journal in response to “Use of mobile phones and risk of brain tumours: update of Danish cohort study”

(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

L Lloyd Morgan, Sr. Research Fellow
Environmental Health Trust
Letter to the Editor of the British Medical Journal in response to “Use of mobile phones and risk of brain tumours: update of Danish cohort study”

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.

Dorothy M Gujral, Clinical Research Fellow
Royal Marsden Hospital
Letter to the Editor of the British Medical Journal in response to “Use of mobile phones and risk of brain tumours: update of Danish cohort study”

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 evices/manufacturers of each phone. Design differences between manufacturers may influence risk. The authors’ conclusions should therefore be interpreted with these confounders in mind.

Denis L Henshaw, Emeritus Professor of Human Radiation Effects
School of Chemistry University of Bristol Cantocks Close, Bristol, BS8 1TS
Letter to the Editor of the British Medical Journal in response to “Use of mobile phones and risk of brain tumours: update of Danish cohort study”

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 utilizes 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.

4. Kheifets L, Monroe J, Vergara X, Mezei G, Afifi AA. 2008. Occupational electromagnetic fields and leukaemia and brain cancer: An update to two meta-analyses. JOEM 50:677-688.

5. Gould JL. 2010 Animal Navigation: Longitude at Last. Curr Biol 21;R226 DOI: 10.1016/j.cub.2011.01.063

6. Lohmann KJ. 2010. Magnetic-field perception. Nature 464:1140-1142.

7. Phillips JB, Muheim R, Jorge PE. 2110. A behavioral perspective on the biophysics of the light-dependent magnetic compass: a link between directional and spatial perception? J Exp Biol 213, 3247-3255. doi:10.1242/jeb.020792.

8. Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ. 1992. Magnetite biomineralization in the human brain. PNAS USA 89:7683-7687.

9. Vanderstraeten J, Gillis P. 2010. Theoretical Evaluation of Magnetoreception of Power-Frequency Fields. Bioelectromagnetics 31:371- 379.

10. Kirschvink JL. 1996. Microwave Absorption by Magnetite: A Possible Mechanism for Coupling Nonthermal Levels of Radiation to Biological Systems. Bioelectromagnetics 17:187-194.

11. Brocklehurst R, McLauchlan KA 1996. Free radical mechanism for the effects of environmental electromagnetic fields on biological systems. Int J Radiat Biol. 69:3-34.

12. Ritz T, Wiltschko R, Hore PJ, Rodgers CT, Stapput K, Thalau P, Timmel CR, Wiltschko W. 2009. Magnetic compass of birds is based on a molecule with optimal directional sensitivity. Biophys J. 96, 3451-3457. (doi:10. 1016/j.bpj.2008.11.072)

13. V?cha M, P??ov? T,and Mark?ta Kv??alov? M. 2009. Radio frequency magnetic fields disrupt magnetoreception in American cockroach. J Exp Biol. 212;3473-3477.

14. ICNIRP Guidelines 1998: International Commission on Non-Ionizing Radiation Protection: Guidelines for limiting exposure to time-varying electric, magnetic and electromagnetic field (up to 300 GHz). Health Phys 74(4):494-522.

15. Foley LE, Gegear1 RJ, Reppert SM. 2011. Human cryptochrome exhibits light-dependent magnetosensitivity. Nature Comm. DOI: 10.1038/ncomms1364

16. Henshaw DL, Reiter RJ. 2005. Do magnetic fields cause increased risk of childhood leukaemia via melatonin disruption? Bioelectromagnetics Suppl 7:S86-S97.

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

Alasdair M Philips, Engineer and scientist
Powerwatch (UK NGO)
Letter to the Editor of the British Medical Journal in response to “Use of mobile phones and risk of brain tumours: update of Danish cohort study”

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?

Philippe Charlier, MD, PhD Forensic Department, Garches (AP-HP, UVSQ)
Letter to the Editor of the British Medical Journal in response to “Use of mobile phones and risk of brain tumours: update of Danish cohort study”

This important and huge cohort study presents however strong limits. It takes into account only individual subscription holders, without including those who have only one professional cellphone. More, the daily duration of use of the cellphone is not known, the subscribtion holders not having been questioned on that point.


These two limits are important, as it is the intensive use of a cellphone that could cause an increased risk of central nervous system tumour. If Frei et al. do not exclude that an increase in the risk appears for the very large users of cellphones (for example for a use of more than 15 years), further studies with more precise data are necessary before excluding any sanitary risk of mobile phones.

Margaret Meade Glaser, MBA
Board of Directors for the EMR Network
Letter to the Editor of the British Medical Journal in response to “Use of mobile phones and risk of brain tumours: update of Danish cohort study”

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

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