Evaluation of mobile phone and cordless phone use and glioma risk

In a recent article published in a scientific journal we evaluated use of wireless phones (mobile phones and cordless phones; DECT) and glioma risk. Glioma is a brain tumour that is one of the most common types. We used the Sir Austin Bradford Hill nine viewpoints on association or causation published in 1965 at the height of the debate on smoking and lung cancer risk. The same method can be used for other environmental agents and cancer risk.

As Bradford Hill pointed out not all nine viewpoints need to be fulfilled. The current knowledge may not exist in certain aspects. However, certain aspects such as first exposure before the onset of the disease and a dose-response relationship should exist.

Our evaluation was based on human epidemiological studies and findings in laboratory studies on animals and in cell cultures. Our conclusion was all nine viewpoints by Bradford Hill are fulfilled and that glioma is caused by radiofrequency (RF) radiation:

The nine Bradford Hill viewpoints on association or causation regarding RF radiation and glioma risk seem to be fulfilled in this review. Based on that we conclude that glioma is caused by RF radiation. Revision of current guidelines for exposure to RF radiation is needed.

RF radiation as a human carcinogen was evaluated by the International Agency for Research on Cancer (IARC) at WHO in May 2011. The conclusion was that such exposure is a possible human carcinogen, Group 2B according to the definition by WHO. The scientific evidence has increased since then and RF radiation should now be regarded as a human carcinogen, Group 1. An updated new evaluation by IARC is urgently needed.

We discuss in our article scientific controversy in this area including industry influence and ties between researchers and industry. A key player is the International Commission on Non-Ionizing Radiation (ICNIRP), a private NGO based in Germany that selects its own members and that does not publish funding sources. The ICNIRP guideline for RF radiation is extremely high and only based on short time thermal (heating) effects. Non-thermal effects are disregarded, that is a vast majority of studies on negative health effects from RF radiation not based on tissue heating. This gives in practice a ‘green card’ to roll out this technology since the high ICNIRP guideline is rarely compromised. Several governmental organizations in different countries have adopted the high ICNIRP level for exposure.

A new Health Criteria (Monograph) on RF radiation and health is under production by WHO. As discussed previously this document is biased towards the no-risk paradigm thereby neglecting published health risks from RF radiation. It has turned out that almost all persons in the core group for the WHO Monograph are present or former members of ICNIRP, see Table.

 

Table. Members of WHO Monograph core group and their involvement in other groups

Name WHO ICNIRP UK/AGNIR SSM SCENIHR
Simon Mann X X X
Maria Feychting X X X X*
Gunnhild Oftedal X X
Eric van Rongen X X X
Maria Rosaria Scarfi X X* X X
Denis Zmirou X

*former

WHO: World Health Organization

ICNIRP: International Commission on Non-Ionizing Radiation Protection

AGNIR: Advisory Group on Non-Ionising Radiation

SSM: Strålsäkerhetsmyndigheten (Swedish Radiation Safety Authority)

SCENIHR: Scientific Committee on Emerging and Newly Identified Health Risks

 

Thus, this fact – being member of both ICNIRP and the core group – is a serious conflict of interest. One would rarely expect that the core group members would present an evaluation that is in conflict with their own evaluation in ICNIRP. It has been requested that these persons should be replaced by experts with no conflict of interest, a most reasonable viewpoint.

As a matter of fact the Ethical Board at the Karolinska Institute in Stockholm, Sweden, concluded already in 2008 that being a member of ICNIRP may be a conflict of interest that should be stated in scientific publications (Karolinska Institute Diary Number 3753-2008-609). This is not done as far as can be seen in publications by ICNIRP persons such as members of the WHO core group.

The fifth generation (5G) of RF radiation is now under establishment. This is done without proper dosimetry or studies on potential health effects. The major media attention is a ‘love song’ to all possibilities with this technology such as so called self-driving cars, internet of things etc. Consequences for human health and environment such as wild life and vegetation are not discussed. Politicians, governmental agencies and media are responsible for the skewed debate. The layman is not informed about opposite opinions on this development. Health effects from RF radiation in media is a ‘no issue’ at least in Sweden but also in most other countries.

More results from Interphone confirm glioma risk associated with use of mobile phones

The Interphone study on use of mobile phones and brain tumour risk included 13 countries during the study period 2000 – 2004. The major results were published after a delay of 6 years in 2010. In the last decile of cumulative exposure > 1,640 h a statistically significant increased risk for glioma was found, OR = 1.40, 95 % CI =1.03-1.89. In the other categories of cumulative use a decreased risk was found. Bias and confounding were discussed as potential reasons for that. Analysing only subjects with regular use of a mobile phone yielded OR = 1.82, 95 % CI = 1.15-2.89 in the group with highest cumulative use.

There was an age difference between cases and controls in the Interphone study and furthermore cases and the matched controls were interviewed at different time periods, controls usually later than cases. This is problematic for mobile phone use with rapid penetration of the use in the population. In a recently published alternative analysis, cases and controls nearest in age and time for interview were included. The association between mobile phone use and glioma was strengthened thereby. Thus, among regular users in the 10th decile (> 1,640 h) cumulative use gave OR = 2.82, 95 % CI = 1.09-7.32. The authors concluded that there was ‘stronger positive association among long-term users and those in the highest categories of cumulative call time and number of calls.’.

Since the IARC evaluation in 2011 on exposure to radiofrequency radiation form mobile phones, and other devices that emit such radiation, and brain tumour risk additional research has strengthened the association. It is by now time to re-evaluate the scientific evidence on the cancer risk from radiofrequency radiation.

New results from Interphone confirm glioma risk associated with use of mobile phones

The Interphone study included 13 countries during the study period 2000 – 2004. The major results were published after a delay of 6 years in 2010. In a new publication 12 years after the study period, the intracranial distribution of glioma in relation to radiofrequency (RF) radiation from mobile phones was analyzed. Tumour localization for 792 regular mobile phone users was analyzed in relation to distance from preferred ear for mobile phone use.

In Table 2 five categories for the distance were used with > 115.01 mm as the reference category (α = 1.0).  An association with distance from preferred side of mobile phone use to center of tumour was found; the closer the distance the higher the risk. The highest risk was found in the group with the closest distance (0-55 mm) yielding α = 2.37, 95 % Confidence Interval (CI) = 1.56-4.56.

The same association was seen if distance was based on point with highest Specific Absorption Rate (SAR) instead of preferred ear and if using a model assuming that the preferred side of phone use was not exclusively used (“mixing proportion”). The latter model generated higher risk estimates than the other two but with wider confidence intervals.

In Table 3 tumour size, duration of phone use, cumulative phone use, cumulative number of calls were analyzed. Although not statistically significant, higher risks with decreasing distance were found in the upper levels of these dichotomized covariates.

α and 95 % CI in shortest distance group 0-55 mm from preferred ear to tumour center

Tumour size                        α                    95 % CI

≤18 cm3                              1.96               1.51 – 3.66

18 cm3                                4.09               1.90 – 12.0

Duration of phone use

<6 years                              2.02               1.31 – 4.28

≥6 years                              3.27               1.92 – 11.3

Cumulative phone use

<200 hours                          1.57                1.29 – 3.36

≥200 hours                          4.06                2.03 – 11.6

Cumulative number of calls

<4,000                                 1.55                  1.25 – 3.42

≥4,000                                 3.56                 2.05 – 9.88

The authors concluded that ‘Taken together, our results suggest that ever using a mobile phone regularly is associated with glioma localization in the sense that more gliomas occurred closer to the ear on the side of the head where the mobile phone was reported to have been used the most. However, this trend was not related to amount of mobile phone use, making it less likely that the association observed is caused by a relationship between mobile phone use and cancer risk.’

The first part although correct is misleading. The correct statement would be that the risk was highest for glioma closer to the ear as would be expected based on the exposure to RF radiation. The last sentence should have indicated that although not statistically significant, the risk was highest in the group with longest duration of phone use, highest cumulative phone use and number of calls. This is a pattern one would expect if there is an association between mobile phone use and glioma.

A similar tendency to not correctly downplaying the association is found in the abstract: ‘The association was independent of the cumulative call time and cumulative number of calls.’ Since many persons read only the abstract, as also presented in PubMed, correct presentation of the results including αs and 95 % CIs would have been more relevant.

The correct interpretation of this study is simply that it confirms an increased risk for glioma associated with mobile phone use.

 

Footnote: The α values represent the change in risk of observing a tumor within the given interval in comparison with the baseline intensity.

Letter to WHO regarding brain tumour risk associated with exposure to radiofrequency fields

We have previously commented on the many scientific mistakes in the WHO draft Monograph on radiofrequency fields and health effects. Since there has not been any reaction we have sent the following letter asking for revision. A similar letter was send to IARC asking for new cancer risk evaluation.

 

World Health Organization                                                              4 August, 2015

 

Dr Margaret Chan, Director General

World Health Organization

Avenue Appia 20, 1211 Geneva 27

Geneva, Switzerland

 

Emelie van Deventer, Team Leader

Radiation Programme Department of Public Health,

Environmental and Social Determinants of Health,

World Health Organization

Geneva, Switzerland

 

Dear Ms. Margaret Chan

Dear Ms. Emelie van Deventer

 

Further Comments on the WHO draft: Radio Frequency fields: Environmental Health Criteria Monograph

On 15 December, 2014 we submitted comments on the WHO draft on radio frequency fields and health. Since we have not got a satisfactory reply from WHO, not seen a revision of the draft, and adding to that more published studies that reinforce the increased risk for certain brain tumours associated with use of wireless phones we want to submit the following, additional comments.

The brain is the primary target organ for exposure to radiofrequency electromagnetic fields (RF-EMF) during the use of the handheld wireless phone. This has given concern of an increased risk for brain tumours. The carcinogenic effect of RF-EMF on humans was evaluated at a meeting during 24 – 31 May 2011 at the International Agency for Research on Cancer (IARC) at WHO in Lyon, France. One of us (LH) was part of the expert group. The Working Group categorised RF-EMF from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields in the frequency range 30 kHz–300 GHz, as a Group 2B, i.e. a possible, human carcinogen (http://monographs.iarc.fr/ENG/Monographs/vol102/mono102.pdf).

Since then more studies have been published that strengthen the association between use of wireless phones (mobile and cordless phones) and increased risk for brain tumours. We have performed long-term research in this area and in the following we give a short up-dated summary of our findings based on research since the 1990’s. In our publications relevant information can be found also on other studies, as well as discussions of the current scientific evidence.

Glioma:

Glioma is a malignant brain tumour (“brain cancer”), and the most common type is glioblastoma multiforme with a poor prognosis. We have published a statistically significant increased risk for glioma among users of both mobile and cordless phones. The risk increased with latency (time from first use of the phone until tumour diagnosis) and cumulative number of hours for use. Highest risk was found in the area of the brain with highest exposure to RF-EMF. All these results are of biological relevance; that is what would be expected for a causal association. The full paper can be read here:

http://www.pathophysiologyjournal.com/article/S0928-4680(14)00064-9/pdf

Meningioma:

Menigioma is mostly a benign brain tumour and accounts for about 30 % of all intracranial tumours. The incidence is approximately 2-times higher in women than in men. No conclusive evidence of an association between use of mobile and cordless phones and meningioma was found in our study. However, taking the long latency periods that have been reported for the increased meningioma risk associated with exposure to ionizing radiation it is still too early to make a definitive risk assessment. Results for even longer latency periods of wireless phone use than in our study are desirable, see more details here:

http://www.spandidos-publications.com/or/33/6/3093

Acoustic neuroma:

Acoustic neuroma or Vestibular Schwannoma is a rare benign tumour in the eighth cranial nerve that leads from the inner ear to the brain. It grows slowly and does not undergo malignant transformation, but may give compression of vital brain stem centres. Tinnitus and hearing problems are usual first symptoms of acoustic neuroma. We published a clear, statistically significant, association between use of mobile and cordless phones and acoustic neuroma. The risk increased with time since first use. For use of both mobile and cordless phones the risk was highest in the longest latency group. Tumour volume increased per 100 hours of cumulative use and year of latency for wireless phones indicating tumour progression from RF-EMF. The whole study can be read here:

http://www.spandidos-publications.com/ijo/43/4/1036

Brain tumour prognosis:

A causal association would be strengthened if use of wireless phones has an impact on the survival of glioma patients. We analyzed survival of 1,678 glioma patients in our case-control studies 1997-2003 and 2007-2009. Use of wireless phones in the > 20 years latency group (time since first use) yielded increased hazard ratio (HR) = 1.7, 95 % confidence interval (CI) = 1.2-2.3 for glioma, i.e. decreased survival. Increased HR was found for use of both mobile and cordless phones. Highest HR was found for cases with first use before the age of 20 years. These results strengthen a causal association between use of wireless phones and glioma. The publication can be read here:

http://www.mdpi.com/1660-4601/11/10/10790

Risk in different age groups of first use:

In our glioma study we found highest risk for subjects with first use of mobile or cordless phone before the age of 20, see Table 8 in the publication:

http://www.pathophysiologyjournal.com/article/S0928-4680(14)00064-9/pdf

We published similar results for acoustic neuroma and use of mobile phones, see Table 21.2:

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.433.7480&rep=rep1&type=pdf

Children and adolescents are more exposed to RF-EMF than adults due to thinner skull bone, higher conductivity in the brain tissue, and a smaller head. The developing brain is also more vulnerable than in adults and it is still developing until about 20 years of age. The finding of higher risk in young persons is worrying, not the least due to the high prevalence of use of wireless phones in children and adolescents.

Brain tumour incidence:

It is not correct to claim that the incidence of brain tumours has not increased in the Scandinavian countries. The age-standardized incidence of brain tumours increased dramatically in Denmark with +41.2 % among men and +46.1 % among women during 2003-2012 (http://www.ssi.dk/Aktuelt/Nyheder/2013/~/media/Indhold/DK – dansk/Sundhedsdata og it/NSF/Registre/Cancerregisteret/Cancerregisteret 2012.ashx).

Due to the well-known under-reporting of brain tumours to the Swedish Cancer Registry we studied brain tumour rates using the Swedish National Inpatient Register and the Causes of Death Register (see http://www.mdpi.com/1660-4601/12/4/3793/htm ). In summary we found a statistically significant increasing rate of not specified brain tumours from 2007 in the Inpatient Register and from 2008 in the Causes of Death Register. Our study indicated that several of these tumours were never reported to the Swedish Cancer Register. The results are in accordance with a reasonable latency period for use of wireless phones, e.g. mobile phones, see Figures 5 and 6 in our publication. Thus, the Swedish Cancer Register data cannot be used to dismiss an increased risk for brain tumours associated with use of wireless phones. On the contrary our study is consistent with an association considering a reasonable tumour induction period.

Mechanistic aspects:

Reactive oxygen species:

RF-EMFs do not cause direct DNA damage. On the other hand numerous studies have shown generation of reactive oxygen species (ROS) that can cause oxidative damage of DNA. This is a well-known mechanism in carcinogenesis for many agents. The broad biological potential of ROS and other free radicals makes radiofrequency radiation a potentially hazardous factor for human health, not only cancer risk but also other health effects. A recent update can be read here:

http://informahealthcare.com/doi/abs/10.3109/15368378.2015.1043557

-Tumour promotion:

Tumour promotion by RF-EMF exposure was reported in 2010 in a study on mice: http://www.ncbi.nlm.nih.gov/pubmed/20545575. These findings were recently replicated and add to the relevance of tumour risk: http://www.ncbi.nlm.nih.gov/pubmed/25749340

-p53:

The p53 protein is a transcription factor that plays a vital role in regulating cell growth, DNA repair and apoptosis, and p53 mutations are involved in disease progression. In a recent study it was found that use of mobile phones for ≥3 hours a day was associated with increased risk for the mutant type of p53 gene expression in the peripheral zone of astrocytoma grade IV (glioblastoma multiforme), and that this increase was statistically significant correlated with shorter overall survival time:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178273/

 These results are in agreement with the decreased survival for patients with astrocytoma grade IV (glioblastoma multiforme) associated with long-term use of mobile phones and cordless phones that we reported in 2014, see above the section on prognosis.

Causality:

To further evaluate strengths of evidence Sir Austin Bradford Hill wrote in the 1960’s a famous article on association or causation at the height of the tobacco and lung cancer controversy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1898525/pdf/procrsmed00196-0010.pdf

Hill offered a list of nine aspects of an association to be considered when deciding if an association is causal. However, he did not request all nine viewpoints to be fulfilled for causality. We used the Hill criteria to evaluate the causality on brain tumour risk from RF-EMF emitted from wireless phones. We concluded that based on the Hill criteria, glioma and acoustic neuroma should be considered to be caused by RF-EMF emissions from wireless phones and regarded as carcinogenic to humans, classifying it as Group 1 according to the IARC classification. See more here:

http://www.degruyter.com/view/j/reveh.2013.28.issue-2-3/reveh-2013-0006/reveh-2013-0006.xml

Conclusion:

Our results are in agreement with other studies such as the international Interphone study and the French CERENAT study. This is discussed in more detail in e.g. our article on glioma risk, see also:

http://www.pathophysiologyjournal.com/article/S0928-4680(12)00110-1/pdf

The so called Danish cohort study on mobile phone users has been taken as evidence of no risk. However, the many shortcomings as reviewed elsewhere makes the study inconclusive regarding assessment of cancer risk. It should not be cited as evidence of no risk, for more details see: http://www.degruyter.com/view/j/reveh.2012.27.issue-1/reveh-2012-0004/reveh-2012-0004.xml?format=INT

In summary there is consistent evidence of increased risk for glioma and acoustic neuroma associated with use of mobile phones and cordless phones. Furthermore, the risk is highest for persons with first use before the age of 20, which is of special concern. Our conclusion is that RF-EMF should be regarded as a human carcinogen. The IARC classification should be updated to at least Group 2A, a probable human carcinogen. Current guidelines for exposure need to be urgently revised. The WHO Monograph draft on this issue is based on selective inclusion of studies and wrong assessment of the evidence of increased risk. Thus the Danish cohort study on mobile phone users and the Swedish Cancer Register data cannot be used as evidence of no increased risk. It is important that the public and decision makers are given correct information about the cancer risk so that they can make decisions based on correct data and take precautions. Otherwise there is an obvious risk of forthcoming increasing impairment of human health and increasing numbers of cancer in the population. We anticipate correction of the Monograph and your reply to this letter no later than 15 September, 2015. If you so wish our research group may of course give a presentation at WHO on this topic.

Yours sincerely,

 

Lennart Hardell, MD, PhD

Department of Oncology

University Hospital

SE-701 85 Örebro

Sweden

 

Michael Carlberg, MSc

Department of Oncology

University Hospital

SE-701 85 Örebro

Sweden

Moving radiofrequency radiation from Group 2B to 1 as a human carcinogen

The carcinogenic effect of radiofrequency electromagnetic fields (RF-EMF) on humans was evaluated at a meeting during 24 – 31 May 2011 at the International Agency for Research on Cancer (IARC) at WHO in Lyon, France. The Working Group categorised RF-EMF from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e. a ‘possible’, human carcinogen.

After that meeting supportive evidence has come from e.g. the French CERENAT study and also our recent publication on glioma. An increased risk for acoustic neuroma associated with use of wireless phones was published by our research group after the meeting giving pooled results of our study periods 1997-2003 and 2007-2009. Also other studies have reported similar findings.

We evaluated the Hill viewpoints on association and causation used in the 1960’s in the debate on lung cancer risk among smokers. Using these viewpoints our summary was that RF-EMF exposure should be a Group 1 carcinogen according to IARC criteria. There is now a petition to support that notion aiming at alerting IARC to classify such exposure to cause human cancer. Those who want to support the petition can follow this link.

New study confirms increased risk for glioma associated with use of mobile phones and cordless phones

We published recently a pooled analysis of our case-control studies on glioma and use of mobile phones and cordless phones. The study has been published in Pathophysiology after pre-review and can be accessed via Internet. The results confirm a statistically significant increased risk for glioma and the risk increases with time from first use of the wireless phone and number of hours for use over the years. The risk is highest on the same side of the brain as the phone has been used, especially in the area with the highest exposure to microwaves, the temporal lobe, which would be expected.

These studies strengthen the 2011 classification by IARC at WHO that the microwave exposure is a ‘Possible human carcinogen’, Group 2B. In fact using the Hill viewpoints on association and causation it should be classified as Group 1, the agent causes human cancer. We have explored that fact in more detail in a previous article. The present results confirm that classification.

Our results have gained interest in many countries after a press release by Reuters and have also been discussed in the Finnish Medical newspaper. However, these worrying results for human health have not been discussed at all in Sweden, so the layman is uniformed about how important it is to avoid such exposure.

New study confirms increased risk for gliomas associated with use of mobile phone

On 9 May 2014 a new French case-control study on mobile phone use and brain tumour risk in the CERENAT study was published online. It confirms an increased risk for gliomas in the heaviest users. Life-time cumulative use > 896 hours produced odds ratio (OR) = 2.89, 95 % confidence interval (CI) = 1.41-5.93. Number of calls (> 18 360 calls) gave OR = 2.10, 95 % CI = 1.03-4.31. Considering a 5-year latency period (5-year censorship) increased the risk further in the last decile of cumulative use to OR = 5.30, 95 % CI = 2.12-13.23.

Increased risk was found for analogue phone use; OR = 3.75, 95 % CI = 0.97-14.43, and digital mobile phone use only; OR = 2.71, 95 % CI = 1.03-7.10. Risks were higher for temporal tumours, occupational and urban mobile phone use. Unfortunately the study did not include use of cordless phones (DECT) which leads to underestimate of the risks since such use was regarded as no exposure to radiofrequency electromagnetic fields (RF-EMF).

The study included also cases with meningioma. A statistically significant increased risk was found for cumulative duration of calls > 896 hours yielding OR = 2.57, 95 % CI = 1.02-6.44. However, overall the results were less consistent for an association than for gliomas.

This study reports important findings that add to the conclusion that gliomas are caused by exposure to RF-EMF. It strengthens the conclusions in our article on causation using the Hill viewpoints on causation and association.