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Archive for the ‘Bradford Hill’ Category

I en ny artikel publicerad i en vetenskaplig tidning har vi utvärderat sambandet mellan användning av trådlösa telefoner (mobiltelefoner och trådlösa bordstelefoner; DECT) och gliom, d.v.s. en av de vanligaste typerna av hjärntumörer. Vi använde oss av de synpunkter på ett orsakssamband som publicerades 1965 av Sir Austin Bradford Hill i England. Han utarbetade 9 ”kriterier” som användes i kontroversen rökning och lungcancer. Samma metod kan även användas för att utvärdera sambandet mellan andra miljögifter och cancer.

Kravet är inte att alla kriterier behöver uppfyllas, eftersom kunskapsläget för tillfället kan vara bristfälligt inom ett visst område, som Bradford Hill påpekade. Dock gäller vissa förhållanden, t.ex. att exponeringen bör föregå sjukdomen, det bör finnas ett dos-effektsamband, d.v.s. att högre exponering ger en högre risk, och att det bör finnas stöd i experimentella studier.

Vår utvärdering grundas på studier på människa och laboratoriestudier på djur och i cellkulturer. Vår slutsats är att de synpunkter som Bradford Hill publicerat om ett orsakssamband är uppfyllda och att gliom orsakas av den radiofrekventa (RF) strålningen från trådlösa telefoner:

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.

Sambandet utvärderades av International Agency for Research on Cancer (IARC) vid WHO i maj 2011. Slutsatsen blev att RF strålning är möjligen cancerframkallande för människan (Grupp 2B enligt deras definition). Det vetenskapliga stödet för ett samband har därefter ökat betydligt och RF strålning bör nu anses vara en cancerrisk för människan (Grupp 1). Ny utvärdering av IARC är nödvändig.

I vår nya artikel beskriver vi även vetenskapliga kontroverser inom området med starkt inflytande från industrin, som givetvis inte vill påvisa några risker. En nyckelspelare är International Commission on Non-Ionizing Radiation (ICNIRP), en privat organisation i Tyskland som utser sina egna medlemmar och som inte öppet deklarerar sina bidragsgivare. ICNIRP är industrivänlig och har dessutom ett stort inflytande inom WHO. ICNIRP anger mycket hög riktlinje (guideline) för RF strålning vilket i praktiken ger grönt kort för olika typer av apparater/prylar som avger RF strålning. Detta möjliggörs genom att ICNIRP grundar sitt ’gränsvärde’ på enbart uppvärmning och bortser från alla resultat som inte beror på uppvärmning av vävnad, så kallad ‘non-thermal’ effekt. Det innebär att ICNIRP bortser från en mycket stor del av den vetenskapliga litteraturen inom området.

Vid WHO pågår arbetet med ett nytt kriteriedokument om RF strålning och hälsa. Tyvärr är nästan samtliga personer som har det huvudsakliga ansvaret (core group) för monografin medlemmar av ICNIRP, se tabell nedan. Detta är en intressekonflikt som tyvärr inte har åtgärdats av WHO. Det har kommit krav på att dessa personer bör bytas ut, vilket är rimligt.

 

Medlemmar inom WHO för nytt kriteriedokument om RF strålning och hälsa och deras medlemskap i ICNIRP och andra grupper

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

 

Etikprövningsnämnden vid Karolinska Institutet i Stockholm bedömde redan 2008 att medlemskap i ICNIRP kan utgöra en intressekonflikt och bör anges då en medlem av ICNIRP uttalar sig om hälsorisker av den radiofrekventa strålningen t ex från trådlösa telefoner, basstationer och annan trådlös kommunikation (Karolinska Institute Diary Number 3753-2008-609). Detta beslut tycks ignoreras helt.

Den femte generationen, 5G, av RF strålning står för dörren. Den så kallade utvecklingen går med expressfart utan att vi har debatt i media, bland beslutsfattare eller allmänhet om konsekvenser för människa och miljö. Teknikfixering och telekomindustrins vinstintresse är pådrivande utan att negativa effekter diskuteras.

 

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Det första utkastet till monografi om hälsoeffekter av radiofrekventa fält från WHO innehåller många sakfel som vi påpekat tidigare. Vi har nu påtalat detta på nytt och skickat till WHO brev enligt nedan. IARC har fått samma brev med begäran om ny utvärdering av cancerrisker.

 

 

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

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Upprop till IARC med begäran att RF-EMF ska anses orsaka cancer, Grupp 1. Den som önskar stödja detta upprop kan följa denna länk.  Medborgarförslaget kan läsas nedan. Närmare 5 000 personer runt om i världen stödjer uppropet för närvarande. Uppropet är fortfarande öppet för de som önskar stödja det.

Joint Statement

We—the undersigned organizations, doctors, and scientists—wholeheartedly support the scientific findings of a connection between cancer and RF/EMF radiation. For the sanctity of human life, especially our children, we respectfully request that:

  • WHO/IARC immediately conducts the appropriate scientific review within IARC to move RF/EMF radiation from its current class 2B to class 1, known carcinogen based on review of the complete scientific database.
  • As is the policy of the WHO with Smoking/Cancer related issues, we respectfully request that the WHO and IARC not permit any conflicts of interests amongst the scientists, doctors, policy making/administrating officials, or anyone serving in any other capacity determining classifications of carcinogenicity and policy decisions regarding EMFs and Cancer.
  • Specifically we respectfully request that any scientist, doctor, policy making/administrating official, or anyone serving in any capacity in WHO and IARC not receive now or in the near future any monetary compensation from the wireless industry or any company that produces products that emit or receive RF radiation or benefit from such products or companies – in the form of research grants, consulting fees or any other form of compensation including payments to any relative of the scientist or colleague in close association.

 We respectfully request that these conflicts be vehemently policed and monitored to maintain the integrity of the classifications, assure absolute transparency and ensure safety of the public.

According to Dr. Lennart Hardell, MD, PhD, and oncologist:

”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.” http://www.ncbi.nlm.nih.gov/pubmed/24192496

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Den 9 maj 2014 publicerades resultaten av en ny fransk studie om sambandet mellan användning av mobiltelefon och risken för hjärntumörer. Det är en fall-kontroll studie och ingår i CERENAT. Undersökningen bekräftar en statistiskt säkerställd ökad risk för de personer som är de tyngsta användarna av mobiltelefoner. Livslång kumulativ användning > 896 timmar gav oddskvot (OR) = 2,89, 95 % konfidensintervall (CI) = 1,41-5,93. Antal samtal > 18 360 gav OR = 2,10, 95 % CI = 1,03-4,31. För personer som använt sin mobiltelefon första gången minst 5 år före diagnosen av gliom ökade risken ytterligare till OR = 5,30, 95 % CI = 2,12-13,23.

Studien visar ökad risk för analoga telefoner; OR = 3,75, 95 % CI = 0,97-14,43, men även för endast digital typ; OR = 2,71, 95 % CI = 1,03-7,10. Risken är högre för tumörer i tinningloben av hjärnan, yrkesmässig användning och i stadsmiljö. Tyvärr inkluderades inte användning av trådlös bordstelefon (DECT) vilket leder till underskattning av risken eftersom även dessa telefoner vid handhållen användning ger exponering till hjärnan av radiofrekventa elektromagnetiska fält (RF-EMF).

Studien inkluderade även meningiom, en godartad hjärntumör. Statistiskt säkerställd ökad risk påvisades för kumulativ användning > 896 timmar med OR = 2,57, 95 % CI = 1,02-6,44. Överlag var dock resultaten för meningiom inte lika entydiga som för gliom för ett samband för användning av mobiltelefoner.

Artikeln redovisar viktiga fynd som starkt bidrar till slutsatsen att gliom orsakas av exponering för RF-EMF. Den styrker resultatet av vår tidigare bedömning om ett orsakssamband om de så kallade Hillkriterierna används.

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Sir Austin Bradford Hill gav i ett berömt tal år 1965 synpunkter på sambandet mellan tobaksrökning och lungcancer. Epidemiologiska studier kan visa en ökad risk på en association men inte att exponeringen i fråga orsakar den åkomma som undersöks, t.ex. cancer.

Bradford Hill presenterade 9 synpunkter, ofta kallade för kriterier, för ett orsakssamband. Han påpekade dock att inte alla villkor behöver vara uppfyllda för att en exponering skall anses orsaka en sjukdom.

Vi har använt oss av dessa villkor för att bedöma om exponering för radiofrekventa fält (mikrovågor) från mobiltelefoner och trådlösa bordstelefoner (DECT) kan orsaka hjärntumörer. Vi finner därvid att de flesta kriterier är uppfyllda och att radiofrekventa fält skall anses orsaka vissa former av hjärntumörer (elakartade och acusticusneurinom). Detta motsvarar Grupp 1 enligt IARC vid WHO ”Sufficient evidence in humans”.

Vår artikel har publicerats efter sedvanlig granskning i den vetenskapliga tidningen Reviews on Environmental Health (DOI 10.1515/reveh-2013-0006). Nedan ges en engelsk sammanfattning av artikeln.

Lennart Hardell and Michael Carlberg

Using the Hill viewpoints from 1965 for evaluating

strengths of evidence of the risk for brain tumors

associated with use of mobile and cordless

phones

Abstract

Background: Wireless phones, i.e., mobile phones and

cordless phones, emit radiofrequency electromagnetic

fields (RF-EMF) when used. An increased risk of brain

tumors is a major concern. The International Agency for

Research on Cancer (IARC) at the World Health Organization

(WHO) evaluated the carcinogenic effect to humans

from RF-EMF in May 2011. It was concluded that RF-EMF

is a group 2B, i.e., a “possible”, human carcinogen. Bradford

Hill gave a presidential address at the British Royal

Society of Medicine in 1965 on the association or causation

that provides a helpful framework for evaluation of

the brain tumor risk from RF-EMF.

Methods: All nine issues on causation according to Hill

were evaluated. Regarding wireless phones, only studies

with long-term use were included. In addition, laboratory

studies and data on the incidence of brain tumors were

considered.

Results: The criteria on strength, consistency, specificity,

temporality, and biologic gradient for evidence of

increased risk for glioma and acoustic neuroma were

fulfilled. Additional evidence came from plausibility and

analogy based on laboratory studies. Regarding coherence,

several studies show increasing incidence of brain

tumors, especially in the most exposed area. Support for

the experiment came from antioxidants that can alleviate

the generation of reactive oxygen species involved in

biologic effects, although a direct mechanism for brain

tumor carcinogenesis has not been shown. In addition,

the finding of no increased risk for brain tumors in subjects

using the mobile phone only in a car with an external

antenna is supportive evidence. Hill did not consider all

the needed nine viewpoints to be essential requirements.

Conclusion: 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.

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