Increased risk for glioma associated with mobile phone use in Interphone Canada

Probabilistic multiple-bias modelling applied to the Canadian data from the INTERPHONE study of mobile phone use and risk of glioma, meningioma, acoustic neuroma, and parotid gland tumors.

Momoli F, Siemiatycki J, McBride ML, Parent MÉ, Richardson L, Bedard D, Platt R, Vrijheid M, Cardis E, Krewski D.

Abstract

We undertook a re-analysis of the Canadian data from the thirteen-country INTERPHONE case-control study (2001-2004), which evaluated the association between mobile phone use and risk of brain, acoustic neuroma, and parotid gland tumors. The main publication of the multinational INTERPHONE study concluded that “biases and errors prevent a causal interpretation”. We applied a probabilistic multiple-bias model to address possible biases simultaneously, using validation data from billing records and non-participant questionnaires as information on recall error and selective participation. Our modelling sought to adjust for these sources of uncertainty and to facilitate interpretation. For glioma, the odds ratio comparing highest quartile of use (over 558 lifetime hours) to non-regular users was 2.0 (95% confidence interval: 1.2, 3.4). The odds ratio was 2.2 (95% confidence interval: 1.3, 4.1) when adjusted for selection and recall biases. There was little evidence of an increase in the risk of meningioma, acoustic neuroma, or parotid gland tumors in relation to mobile phone use. Adjustments for selection and recall biases did not materially affect interpretation in our Canadian results.

The article can be found here.

Comment:

It is noteworthy that statistically significant increased risk was found already at 558+ hours of cumulative use corresponding to 9 min per day during 10 years. This amount is much lower than now used for wireless phones. Total Interphone showed for cumulative call time, 1640 hours or more, odds ratio 1.40 (95% confidence interval 1.03–1.89) for glioma. This corresponds to less than half an hour per day (27 min) during 10 years.

Interphone Canada confirms the increased risk for glioma associated with use of wireless phones, see our recent review, Carlberg, Hardell 2017.

Advertisements

Acoustic neuroma and mobile phone use – another legal decision in Italy

This time a person in Florence who developed acoustic neuroma after long-term use of mobile phone has been awarded economic compensation (articles only available in Italian; google translations to English available here and here). The worker had used his company mobile phone for 10 years, 2-3 hours per day. INAIL (The National Institute for Insurance against Accidents at Work) was again the organisation that was ordered to pay compensation by court order.

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

Letter to New York Times

Ms. Margaret Sullivan, Public Editor                                       July 24, 2015

Ms. Carol Pogas, Reporter

The New York Times

Regarding: Cellphone Ordinance Puts Berkeley at Forefront of Radiation Debate http://www.nytimes.com/2015/07/22/us/cellphone-ordinance-puts-berkeley-at-forefront-of-radiation-debate.html?_r=0

Published online July 21, 2015

Dear Ms. Sullivan and Ms. Pogas,

We have read this article in the New York Times with interest. However, there are several mistakes, and even wrong statements, on the health hazards from exposure to radiofrequency electromagnetic fields (RF-EMF) from cell phones in the article. In the following we want to correct some of the false statements.

The brain is the primary target organ for exposure to 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) 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:

Meningioma 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 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. 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. 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, see more here: http://www.mdpi.com/1660-4601/12/4/3793

Mechanistic aspects:

It is correct that 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

Causality:

To further evaluate strengths of evidence Bradford Hill wrote in the 1960’s a famous article on association or causation at the height of the tobacco and lung cancer controversy. 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 tumor 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. Current guidelines for exposure need to be urgently revised. 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 so called CERENAT study. This is discussed in e.g. our article on glioma risk. 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. It is necessary to give the public correct information on the cancer risk. The precautionary principle should be used to minimize exposure to RF-EMF. Media have an important role to inform in a balanced way. Unfortunately this article in the New York Times is biased towards the no risk assumption. It should be corrected based on facts and not wishful thinking.

 

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.

IARC and asbestos – are there conflicts of interest at a WHO organ?

Recently an article on asbestos and cancer risk was published presenting evidence on former or present persons at IARC depreciating cancer risks from asbestos exposure. One person, Paolo Boffetta, was reported to have been an expert witness for the asbestos industry.

The story on industry infiltration of WHO is described: “In the past, the asbestos industry has succeeded in making inroads inside the World Health Organization (WHO) with the aim of perverting scientific information and promoting continued trade in asbestos, just as the tobacco industry, in the past, infiltrated the WHO. Serious concerns are presently being expressed regarding the fact that the WHO’s International Agency for Research on Cancer (IARC) is putting forth outdated and inaccurate information regarding chrysotile asbestos that minimizes the harm to health that it causes and is collaborating with a discredited institute in Russia and with discredited scientists, who promote use of chrysotile asbestos and deny that it is hazardous to health.” – See more at: http://www.rightoncanada.ca/?p=1761#sthash.PzHXK1Mm.dpuf

The question is if the asbestos story is an isolated occasion or what is on-going at IARC? One recent publication on mobile phones and brain tumour risk is to be considered in that context. Three of the four authors are employees at IARC. Several wrong or misleading facts on brain tumour risk from published studies are presented in the article. Most remarkable is that our recent articles on use of mobile or cordless phones and brain tumour risk are omitted. These publications are well-known to the authors since they were sent to IARC as soon as they were published and even orally presented to one of the authors at IARC, Joachim Schüz. Instead articles of low quality and little value are presented in their paper. Our new articles add further evidence on the increased risk on use of mobile and cordless phones and glioma and acoustic neuroma. So why were they omitted from the IARC article? Are there conflicts of interest at IARC also on this issue?