ArticlePDF Available

Evaluation of Mobile Phone and Cordless Phone Use and Glioma Risk Using the Bradford Hill Viewpoints from 1965 on Association or Causation

Authors:

Abstract and Figures

Objective. Bradford Hill’s viewpoints from 1965 on association or causation were used on glioma risk and use of mobile or cordless phones. Methods. All nine viewpoints were evaluated based on epidemiology and laboratory studies. Results. Strength: meta-analysis of case-control studies gave odds ratio (OR) = 1.90, 95% confidence interval (CI) = 1.31–2.76 with highest cumulative exposure. Consistency: the risk increased with latency, meta-analysis gave in the 10+ years’ latency group OR = 1.62, 95% CI = 1.20–2.19. Specificity: increased risk for glioma was in the temporal lobe. Using meningioma cases as comparison group still increased the risk. Temporality: highest risk was in the 20+ years’ latency group, OR = 2.01, 95% CI =1.41–2.88, for wireless phones. Biological gradient: cumulative use of wireless phones increased the risk. Plausibility: animal studies showed an increased incidence of glioma and malignant schwannoma in rats exposed to radiofrequency (RF) radiation. There is increased production of reactive oxygen species (ROS) from RF radiation. Coherence: there is a change in the natural history of glioma and increasing incidence. Experiment: antioxidants reduced ROS production from RF radiation. Analogy: there is an increased risk in subjects exposed to extremely low-frequency electromagnetic fields. Conclusion. RF radiation should be regarded as a human carcinogen causing glioma.
This content is subject to copyright.
Review Article
Evaluation of Mobile Phone and Cordless Phone Use and
Glioma Risk Using the Bradford Hill Viewpoints from 1965 on
Association or Causation
Michael Carlberg and Lennart Hardell
Department of Oncology, Faculty of Medicine and Health, ¨
Orebro University, 701 82 ¨
Orebro, Sweden
Correspondence should be addressed to Michael Carlberg; michael.carlberg@regionorebrolan.se
Received 17 November 2016; Accepted 29 January 2017; Published 16 March 2017
Academic Editor: Steven De Vleeschouwer
Copyright ©  Michael Carlberg and Lennart Hardell. is is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Objective. Bradford Hill’s viewpoints from  on association or causation were used on glioma risk and use of mobile or cordless
phones. Metho ds. All nine viewpoints were evaluatedbas ed onepidemiology and laboratory studies. Results. Strength: meta-analysis
of case-control studies gave odds ratio (OR) = ., % condence interval (CI) = .–. with highest cumulative exposure.
Consistency: the risk increased with latency, meta-analysis gaveinthe+years’latencygroupOR=.,%CI=...
Specicity: increased risk for glioma was in the temporal lobe. Using meningioma cases as comparison group still increased the risk.
Temporality: highest risk was in the + years’ latency group, OR = ., % CI =.–., for wireless phones. Biological gradient:
cumulative use of wireless phones increased the risk. Plausibility: animal studies showed an increased incidence of glioma and
malignant schwannoma in rats exposed to radiofrequency (RF) radiation. ere is increased production of reactive oxygen species
(ROS) from RF radiation. Coherence: there is a change in the natural history of glioma and increasing incidence. Experiment:
antioxidants reduced ROS production from RF radiation. Analogy: there is an increased risk in subjects exposed to extremely
low-frequency electromagnetic elds. Conclusion. RF radiation should be regarded as a human carcinogen causing glioma.
1. Introduction
In Sir Austin Bradford Hill’s classic epidemiology paper
from , “e Environment and Disease: Association or
Causation?,” he warned not to overrate the value of statistical
signicance since it oen leads people to “grasp the shadow
and loose the substance” of what is in the data []. In the
interpretation of epidemiological studies on cancer there may
be no explanation about how the strength of a link between a
cause and an eect can vary from a “scientic suspicion of
risk”toa“strong association”through“reasonably certainty
and to “causality” which requires the strongest evidence. is
continuum in strengths of evidence, which was illustrated in
Bradford Hill’s paper, written at the height of the tobacco and
lung cancer controversy, is not always explained. is means
that the media and the public may assume that “not causal
means “no link,” with mobile phone use and brain tumour
risk as one example.
In the Interphone study on mobile phone use and brain
tumours an increased risk for glioma was found among the
heaviest mobile phone users []. In an editorial accompany-
ing the Interphone results published in the International Jour-
nal of Epidemiology [], the main conclusion of the results
was described as “both elegant and oracular...(which) toler-
ates diametrically opposite readings.” ey also pointed out
several methodological reasons why the Interphone results
were likely to have underestimated the risks, such as the
short latency period since rst exposures became widespread;
less than % of the Interphone cases had more than 
years of exposure. “None of the today’s established carcino-
gens, including tobacco, could have been rmly identied as
increasing risk in the rst 10 years or so since rst exposure.
e concluding sentences from the Interphone study were
oracular:Overall, no increase in risk of either glioma or
meningioma was observed in association with use of mobile
phones. ere were suggestions of an increased risk of glioma,
Hindawi
BioMed Research International
Volume 2017, Article ID 9218486, 17 pages
https://doi.org/10.1155/2017/9218486
BioMed Research International
and much less so meningioma, at the highest exposure levels,
for ipsilateral exposures and, for glioma, for tumours in the
temporal lobe. However, biases and errors limit the strength of
the conclusions we can draw from these analyses and prevent
acausalinterpretation.” is allowed the media to report
opposite conclusions.
Due to the widespread use of wireless phones (mobile
and cordless phones) an evaluation of the scientic evidence
on the brain tumour risk was necessary. us, in May 
the International Agency for Research on Cancer (IARC)
at WHO evaluated at that time published studies. e
scientic panel reached the conclusion that radiofrequency
(RF) radiation from mobile phones, and from other devices,
including cordless phones, that emit similar nonionizing
electromagnetic eld (EMF) radiation in the frequency range
 kHz–GHz, is a Group B, that is, a “possible,” human
carcinogen [, ]. e IARC decision on mobile phones was
basedmainlyoncase-controlhumanstudiesbytheHardell
group from Sweden [–] and the IARC Interphone study
[, , ]. ese studies provided supportive evidence of
increased risk for brain tumours, that is, glioma and acoustic
neuroma.
No doubt the IARC decision started a worldwide spinning
machine to question the evaluation, perhaps similar to the
one launched by the tobacco industry when IARC was study-
ing and evaluating passive smoking as a carcinogen in the
s []. Sowing confusion and manufacturing doubt is a
well-known strategy used by the tobacco and other industries
[–]; see also Walker [].
A fact sheet from WHO issued in June  shortly
aer the IARC decision in May  stated that “to date, no
adverse health eects have been established as being caused
by mobile phone use” []. is statement contradicted the
IARC evaluation and was not based on evidence at that time
on a carcinogenic eect from RF radiation and was cer-
tainly remarkable since IARC is part of WHO. Furthermore
WHO wrote that “currently, two international bodies have
developed exposure guidelines for workers and for the general
public, except patients undergoing medical diagnosis or treat-
ment. ese guidelines are based on a detailed assessment of
the available scientic evidence.” ese organizations were
the International Commission on Non-Ionizing Radiation
Protection (ICNIRP) and the Institute of Electrical and
Electronics Engineers (IEEE).
ICNIRP is a private organization (NGO) based in Ger-
many that selects its own members. eir source of funding is
not declared. IEEE is the world’s most powerful federation of
engineers. e members are or have been employed in
companies or organizations that are producers or users of
technologies that depend on radiation frequencies, such as
power companies, the telecom industry, and military orga-
nizations. IEEE has prioritized international lobbying eorts
for decades especially aimed at the WHO.
e IARC conclusion was soon also questioned by, for
example, some members of ICNIRP []. e article by
Swerdlow et al. appeared online  July , one month aer
theIARCdecision,andconcludedthat“the trend in the
accumulating evidence is increasingly against the hypotheses
that mobile phone use can cause brain tumours in adults.”
Soon aer that other persons aliated with ICNIRP,
Repacholi and associates, made a review on wireless phone
use and cancer risks. e paper appeared online October ,
 [], with similar conclusions as the Swerdlow et al.
paper [].
e exposure guideline by ICNIRP was established in
[]andwasbasedonlyonthermal(heating)eects
from RF-EMF neglecting nonthermal biological eects. It
wasupdatedin[]andstatedthat“it is the opinion
of ICNIRP that the scientic literature published since the 1998
guidelines has provided no evidence of any adverse eects below
the basic restrictions and does not necessitate an immediate
revision of its guidance on limiting exposure to high frequency
electromagnetic elds. ...erefore, ICNIRP reconrms the
1998 basic restrictions in the frequency range 100 kHz–300 GHz
until further notice.” e guideline still provided by ICNIRP
forRFradiationistoW/m
2depending on frequency. It
should be noted that the ICNIRP guideline is used in most
Europeancountriesaswellasinmanyothercountries.Unfor-
tunately it is based on old data with no acknowledgment of
cancer eects or nonthermal biological eects from RF-EMF
exposure.
ere are a vast number of scientic articles that show
nonthermal adverse health eects from RF radiation. ese,
as well as thermal eects, have been evaluated in several
reports. In contrast to ICNIRP the BioInitiative Reports from
 [], updated in  [], based the evaluation of
health hazards also on nonthermal health eects from RF
radiation. e BioInitiative  Report, with updated ref-
erences, dened the scientic benchmark for possible health
risksasto𝜇W/m2. Considering also chronic exposure
and sensitivity among children the precautionary target level
was proposed to one-tenth of this, – 𝜇W/m2[].
e guideline in the BioInitiative Report obviously con-
tradicts the one proposed by ICNIRP. e ICNIRP exposure
level has been vigorously propagated by that organization in
order to harmonize guidelines worldwide. With few excep-
tionsithasbeenasuccessfulstoryandmostcountrieshave
adopted the ICNIRP guideline. is gives a “green card” to
roll out the technology with increasing RF radiation exposure
to the population, for example, using wireless Internet access
inschools[],sincethehighexposurelevelintheguideline
by ICNIRP is rarely compromised. us, the exposure target
level in the BioInitiative Report is not acknowledged by,
for example, the Swedish Radiation Safety Authority (SSM).
Many persons at the SSM expert panel are also members
of ICNIRP which might be a conict of interests since they
would rarely compromise the ICNIRP view; critical opinions
are not heard. As a matter of fact the Ethical Board at
the Karolinska Institute in Stockholm, Sweden, concluded
already in  that being a member of ICNIRP may be a
conict of interests that should be stated in scientic publi-
cations (Karolinska Institute Diary Number --),
which is however not done to our knowledge.
An association between use of wireless phones and glioma
has not been acknowledged by several scientic bodies in
spite of the IARC classication in May . is is exempli-
edbelow.Infact,ascanbeseeninTablethesamepersons
may appear in dierent expert groups. is would hardly
BioMed Research International
T : Members of WHO Monograph core group and their involvement in dierent other groups.
Name WHO ICNIRP UK/AGNIR SSM SCENIHR
Simon Mann X X X
Maria Feychting X X X X
Gunnhild Oedal X X
Eric van Rongen X X X
Maria Rosaria Scar X XXX
Denis Zmirou X
Former.
WHO: World Health Organization.
ICNIRP: International Commission on Non-Ionizing Radiation Protection.
AGNIR: Advisory Group on Non-Ionising Radiation.
SSM: Str˚
als¨
akerhetsmyndigheten (Swedish Radiation Safety Authority).
SCENIHR: Scientic Committee on Emerging and Newly Identied Health Risks.
make any substantial dierence in the opinion between these
groups. ey may in fact cite themselves by claiming that
various organizations have come to similar conclusion. It is
striking how ICNIRP has inltrated the WHO Monograph
core group making it less likely that the conclusions in that
Monograph will dier from ICNIRP’s conclusions.
ICNIRP (2011). See conclusions at page  [].
e limited duration of data yet available, which
ismainlyforupto10yearsofexposureand
to a lesser extent for a few years beyond this,
also leave uncertainty because of the potential for
long lag period eects, especially for meningioma
which is generally slower growing than glioma.
e possibility of a small or a longer term eect
thus cannot be ruled out. Nevertheless, while one
cannot be certain, the trend in the accumulating
evidence is increasingly against the hypothesis that
mobile phone use causes brain tumours.
AGNIR; Health Protection Agency (2012). See conclusions at
page  [].
In conclusion, despite methodological shortcom-
ings, the available data do not suggest a causal
association between mobile phone use and fast
growing tumours such as malignant glioma in
adults.
Exposure from Mobile Phones, Base Stations, and Wireless Net-
works: A Statement by the Nordic Radiation Safety Authorities
(2013).Seepage[].
e overall data published in the scientic liter-
ature to date do not show adverse health eects
from exposure of radiofrequency electromagnetic
eldsbelowtheguidelinesorlimitsadoptedin
the Nordic countries...Since 2011, a number of
epidemiological studies on mobile phone use and
risk of brain tumours and other tumours of the
head have been published. e overall data on
brain tumour and mobile phone use do not show
an eect on tumour risk.
Health Canada (2015) [31].
Myth: e International Agency for Research on
Cancer (IARC) classied radiofrequency energy as
potentially carcinogenic. is means that I will get
cancer due to my exposure to RF energy.
Fact:eIARCdidnotndadirectlinkbetween
RF energy exposure and cancer.
In 2011, the International Agency for Research on
Cancer (IARC), which is part of the World Health
Organization, classied radiofrequency electro-
magneticeldsaspossiblycarcinogenictohumans
(Group 2B), based on an increased risk for glioma,
a malignant type of brain cancer, associated with
wireless phone use. However, the vast majority of
research to date does not support a link between
RF energy exposure and cancers in humans.
IET: e Institution of Engineering and Technology, UK (2014;
Updated 2016).Seepage[].
BEPAGhasconcludedinthisreportthatthe
balance of scientic evidence to date does not
indicate that harmful eects occur in humans due
to low-level exposure to EMFs. Our examination
of the peer-reviewed literature published in the last
two years has not justied a change in the overall
conclusions published in our previous report in
May 2014.
SCENIHR: Scientic Committee on Emerging and Newly
Identied Health Risks (2015).Seepage[].
Overall, the epidemiological studies on RF EMF
exposure do not indicate an increased risk of brain
tumours, and do not indicate an increased risk for
other cancers of the head and neck region, or other
malignant diseases including childhood cancer.
And looking further down at the same page, we nd the
following.
BioMed Research International
A working group at the International Agency for
Research on Cancer (IARC) within the Mono-
graph programme on the evaluation of carcino-
genic risks to humans classied the epidemiolog-
ical evidence for glioma and acoustic neuroma
as limited and therefore evaluated RF elds as a
possible human carcinogen (IARC, 2013). Based
on studies published since that assessment (update
of the Danish cohort study, the UK cohort study,
further case-control studies, the case-control study
on mobile phones and brain tumours in children
and adolescents, the consistency checks of brain
tumour incidence rates using data from the Nordic
countries and the US), the evidence for glioma has
become weaker.
SSM: Swedish Radiation Safety Authority (2015).Seepage
[].
However, in previous reports the Scientic Coun-
cil of SSM has concluded that studies of brain
tumours and other tumours of the head (vestibu-
lar schwannoma, salivary gland), together with
national cancer incidence statistics from dierent
countries, are not convincing in linking mobile
phone use to the occurrence of glioma or other
tumours of the head region among adults. Recent
studies described in this report do not change
this conclusion although these have covered longer
exposure periods. Scientic uncertainty remains
for regular mobile phone use for time periods
longer than 15 years.
Health Council of the Netherlands Mobile Phones and Cancer,
Part 3. Update and Overall Conclusions from Epidemiological
and Animal Studies (2016).Seepage[].
e available data do not allow drawing conclu-
sions on whether there is an association between
an increased carcinogenic risk and any form of
accumulation of exposure, for instance expressed
in the total call time, or the total amount of
energy deposited by the electromagnetic elds
generated by the phone in the head or in any other
body part....However,itispossiblethatsome
individuals would like to reduce their exposure,
despite the conclusion of the Committee that there
is no consistent evidence for an increased risk for
tumoursinthebrainandotherregionsinthehead
associated with mobile phone use.
SSM: Swedish Radiation Safety Authority (2016).Seepage
[].
Regardingmobilephoneuseandbraintumour
risk, little new data was published and several
papers deal with reanalyses of already published
data. As a consequence, little has changed in the
rating of the evidence.
It should be noted that SSM has never acknowledged
an increased risk for brain tumours associated with use of
wireless phones.
We published in  an article on using the Bradford Hill
viewpoints for brain tumour risk and use of wireless phones
[].Weconcludedthatbasedontheseaspects“glioma
and acoustic neuroma should be considered to be caused
by RF-EMF emissions from wireless phones and regarded as
carcinogenic to humans.” Since then the scientic literature
in this area has expanded considerably. Furthermore, as
exemplied above, aer the IARC evaluation in May ,
several committees have evaluated the evidence on health
risks associated with use of mobile phones. It should also
be noted that these reports are not published in the peer-
reviewed scientic literature and few physicians if at all are
members of these groups. ere seems also to be conict of
interests among these members. It is thus pertinent to make a
new scientic evaluation using the Bradford Hill viewpoints
including the most recent publications.
2. Methods
Sir Austin Bradford Hill used nine viewpoints in his Presi-
dent’s Address on circumstances that may “pass from observed
association to a verdict of causation[]. Our research group
has for long time studied RF radiation and health risks. is
has included continuous surveillance of data bases on new
studies, especially PubMed, but also personal communica-
tions with updated references from other researchers in this
area. is article is partly based on our previous publication
[] and a presentation at the Royal Society of Medicine,
London, October , .
Statistical methods to calculate odds ratios (OR) and %
condence intervals (CIs), to visualize risks using restricted
cubic splines, and to calculate trends in incidence using
joinpoint regression analysis, are presented in our dierent
cited articles. Random-eects model was used for all meta-
analyses using StataSE . (Stata/SE . for Windows; Stata
Corp., College Station, TX, USA).
3. Results
3.1. Strength. e rst viewpoint discussed by Hill is strength
of an association. Table  gives results for highest cumulative
use in hours for mobile phones. Note that in our study
cordless phones were included in the wireless category [].
ehighestgroupofcumulativeuseinCoureauetal.[]
was  h (th percentile) as compared to Interphone
[] , h (th percentile). e results in Hardell and
Carlberg [] were recalculated using the same category for
highest cumulative exposure as in Interphone []. e meta-
analysis yielded OR = ., % CI = .–.. e results
are consistent with a statistically signicant increased risk for
glioma.estudybyTurneretal.[]wasareanalysisof
only parts of the Interphone data and was not included in this
meta-analysis.
Strength of association is also supported by a -country
studyaspartofInterphoneongliomariskinrelationto
estimated RF brain tumour dose from mobile phones []. In
BioMed Research International
T  : Strength. Numbers of cases (Ca), controls (Co), and odds ratio (OR) with % condence interval (CI) for glioma in case-control
studies in the highest category of cumulative use in hours for mobile phone use.
Ca/Co OR % CI
Interphone 2010
Cumulative use , h / . .–.
Coureau et al. 2014
Cumulative use  h / . .–.
Hardell and Carlberg 2015
Cumulative use , h /  . .–.
Tur n er et al. 2 0 1 6 (In terpho ne)
Cumulative use , h / . .–.
Meta-analysis
Cumulative use , h∗∗ / . .–.
Based on Interphone [], Coureau et al. [], and Hardell and Carlberg [].
∗∗ h used for Coureau et al.
Random-eects model used for all meta-analyses, based on test for heterogeneity in the overall group (“all mobile”).
T  : Consistency. Numbers of cases (Ca), controls (Co), and odds ratio (OR) with % condence interval (CI) for glioma and latency in
three dierent case-control studies, Interphone  (mobile phone) [], Coureau et al.  (mobile phone) [], and Hardell and Carlberg
 (wireless phones) [].
Interphone
Appendix 2Coureau et al.

Hardell and Carlberg
 Meta-analysis
Ca/Co OR
(% CI) Ca/Co OR
(% CI) Ca/Co OR
(% CI) Ca/Co OR
(% CI)
Unex posed/ (.)
/ (.)
/, (.)
/, (.)
Latency
– years∗∗ / .
(.–.) / .
(.–.) / .
(.–.) /,.
(.–.)
– years / .
(.–.) / .
(.–.) / .
(.–.) /, .
(.–.)
+ years / .
(.–.) / .
(.–.) /, .
(.–.) /,.
(.–.)
Unexposed Interphone Appendix 2: latency –. years; unexposed in Coureau et al.: not regular user; unexposed Hardell and Carlberg: no use + latency
year.
∗∗– years in Coureau et al.
case-case analyses comparing tumours in the highest exposed
area with tumours located elsewhere the OR for glioma in the
highest exposed area was highest in the group with longest
use,+years,yieldingOR=.,%CI=...
In a case-control study on brain tumours among patients
aged – years at the time of diagnosis an elevated risk was
found based on operator recorded use of mobile phone; OR
= ., % CI = .–. in the longest latency group >.
years[].eresultwasbasedononlyexposedcasesand
 exposed controls. Type of brain tumour was not reported
among these cases.
3.2. Consistency. Similar results should be found by dierent
research groups and in dierent populations. e Interphone
study group included  dierent countries, whereas Coureau
et al. [] covered four areas in France and Hardell and
Carlberg [] covered Sweden. It should be noticed that there
was no overlapping of subjects between our studies and the
Swedish part of Interphone. In these three dierent studies
there is a consistent nding of increased glioma risk increas-
ing with latency, Table . e highest OR was found with
the longest latency, + years. Meta-analysis gave OR = .,
% CI = .–. in the longest latency group. e result
was based on  exposed cases and , exposed controls.
Inclusion criteria for cases and controls diered between
Interphone [] and our study []. us we included subjects
– years in contrast to Interphone including the age
group – years. Furthermore Interphone disregarded use
of cordless phones in contrast to our studies assessing use
of wireless phones: mobile phones and cordless phones. We
analyzed our material in the age group – years and
included use of cordless phones in the “unexposed” group in
our study for the time period – []. is yielded
similar results for glioma in both studies, for example, in
Interphone ipsilateral cumulative mobile phone use , h
OR = ., % CI = .–. and in our study OR = .,
% CI = .–.; contralateral use OR = ., % CI =
.–. and OR = ., % CI = .–., respectively.
BioMed Research International
T  : Specicity. Distribution of average specic absorption rate
(SAR): %.
 MHz , MHz
Right
(i) Brainstem .
(ii) Cerebellum  
(iii) Frontal  
(iv) Occipital
(v) Parietal
(vi) Temporal  
Total .% .%
Le .% .%
Based on Cardis et al. [].
Similar results were also found for glioma in the temporal
lobe; see Table 2in Hardell et al. [].
3.3. Specicity. Specicity deals with specic exposure and
particularsitesandtypesofthedisease.Hereweanalyzeonly
RF radiation. According to one study the temporal lobe is
mostly exposed during use of the handheld mobile phone; see
Table  []. us, highest glioma risk would be expected for
tumours in the temporal lobe.
Table  shows highest risk in the temporal lobe in studies
from three research groups. Results are given for the highest
groupofcumulativeuseforgliomainthetemporallobewith
similar ndings.
As also discussed above under Strength, Cardis et al. []
gave results for glioma in the highest exposed area of the brain
based on estimated RF radiation dose. OR increased with
time since start of mobile phone use yielding highest risk in
the + latency group.
e Interphone study included  countries during the
study period –. e major results were published
aeradelayofyearsin[].Inanewpublicationthe
intracranial distribution of glioma in relation to RF radiation
from mobile phones was analyzed []. Tumour localization
forregularmobilephoneuserswasanalyzedinrelation
to distance from preferred ear for mobile phone use. Five
categories for the distance were used with . mm as the
reference category (𝛼=.).e𝛼values represent the change
in risk of observing a tumour within the given interval in
comparison with the baseline intensity. 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. e highest risk was found in the group with the closest
distance (– mm) yielding 𝛼= ., % CI = .–..
Tumour size, duration of phone use, cumulative phone use,
and cumulative number of calls were analyzed. Although no
statistically signicant dierences were found overall, higher
risks with decreasing distance were found in the upper levels
of these dichotomized covariates; see Table  showing results
for the shortest distance group (– mm).
Our case-control studies included all types of brain
tumours reported to the Swedish Cancer Register regardless
of tumour type []. Assessment of exposure was used
without knowledge of tumour type. We found no consistent
evidence of increased risk for meningioma associated with
use of wireless phones. In one analysis, meningioma cases
(𝑛= ,) were used as the reference entity to glioma cases
(𝑛=1,). Table  shows a statistically signicant increased
risk for glioma associated with ipsilateral use of all phone
types. Ipsilateral mobile phone use gave OR = ., % CI
= .–., and ipsilateral cordless phone OR = ., % CI
= .–.. us the association between RF radiation and
brain tumour risk was specic for glioma.
3.4. Temporality. e temporal association between expo-
sure and disease is important. Both initiation and promo-
tion/progression of the disease are of relevance. Table  shows
highestriskinthegroupwithlongestlatency(timefromrst
exposure to disease). Our study is the only one with results
for latency > years for wireless phone use yielding OR =
., % CI = .–.. Also Interphone [] and Coureau et
al. [] showed increasing risk with latency.
We used restricted cubic splines to visualize the relation-
ship between latency and cumulative ipsilateral use of mobile
phone. e results for latency and ipsilateral mobile phone
use show that there was an increased OR with short latency
and aer some decline an increasing risk with longer latency
(nonlinearity, 𝑝 = 0.01); see Figure  []. is nding is
dierent from the result for contralateral mobile phone use;
see Figure  (nonlinearity, 𝑝 = 0.76). e results were sim-
ilar for cordless phone use, data not in gures (ipsilateral,
nonlinearity, 𝑝 = 0.04; contralateral, nonlinearity, 𝑝 = 0.26).
It should be noted that contralateral use was dened as >%
use on the opposite side of the head compared to the tumour
localization. us, in spite of being coded as contralateral
exposure some ipsilateral tumour exposure (less than %)
may have occurred. ese results are in contrast to menin-
gioma risk with OR close to unity regardless of latency,
Figure ; see also Specicity above.
3.5. Biological Gradient. Sir Bradford Hill mentioned that if
the association shows a biological gradient, dose-response, it
should be more carefully considered. Interphone [] included
, cases and , controls in the analysis. In the last decile
of cumulative exposure , h a statistically signicant
increased risk for glioma was found, OR = ., % CI =
.–.; see Table . In the other categories of cumulative
useadecreasedriskwasfound.Biasandconfounding
were discussed as potential reasons for that. Analyzing only
subjects with regular use of a mobile phone yielded OR = .,
% CI = .–. in the group with highest cumulative use.
ere was an age dierence between cases and controls in the
Interphone material and furthermore cases and the matched
controls were interviewed at dierent time periods, controls
usuallylaterthancases.isisproblematicformobilephones
with rapid penetration of the use in the population. In an
alternative analyses cases and controls nearest in age and time
for interview were included []. e association between
mobile phone use and glioma was strengthened thereby. us
among regular users in the th decile (, h) cumulative
usegaveOR=.,%CI=...
BioMed Research International
T  : Specicity. Numbers of cases (Ca), controls (Co), and odds ratio (OR) with % condence interval (CI) for glioma and all mobile
phone use and in the temporal lobe for mobile phone use , h, in three dierent case-control studies [, , ].
Interphone  Coureau et al.

Hardell, Carlberg

All ,/,.
(.–.) / .
(.–.) /, .
(.–.)
Tempor a l l o be, , h / .
(.–.) /.
(.–.) / .
(.–.)
 h.
T  : Specicity. Estimated elevation in brain tumour risk (𝛼)and
% condence interval (CI) in shortest distance group – mm
compared to reference category . mm from preferred ear to
tumour center. Based on Grell et al. [].
Covariate 𝛼% CI
Tumour s i z e
 cm3. .–.
> cm3. .–.
Duration of phone use
< years . .–.
 years . .–.
Cumulative phone use
< hours . .–.
 hours . .–.
Cumulative number of calls
<, . .–.
, . .–.
0.5
1.5
2.0
1.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
8.0
Odds ratio
4 6 8 10 12 14 16 18 20 22 24 26 282
Mobile phone, ipsilateral, latency (years)
F : Restricted cubic spline plot of the relationship between
latency of ipsilateral mobile phone use and glioma. e solid line
indicates the OR estimate and the broken lines represent the % CI.
Adjustment was made for age at diagnosis, gender, socioeconomic
index (SEI), and year for diagnosis. Population based controls were
used [].
Also Coureau et al. [] found highest risk in the highest
group of cumulative use, h,withOR=.,%CI=
.–. with a statistically signicant trend (𝑝 = 0.02); see
Table.eresultswerebasedonparticipatingcasesand
 participating controls.
0.5
1.5
1.0
2.0
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
8.0
Odds ratio
4 6 8 101214161820222426282
Mobile phone, contralateral , latency (years)
F : Restricted cubic spline plot of the relationship between
latency of contralateral mobile phone use and glioma. e solid line
indicates the OR estimate and the broken lines represent the % CI.
Adjustment was made for age at diagnosis, gender, socioeconomic
index (SEI), and year for diagnosis. Population based controls were
used [].
0.5
1.5
1.0
2.0
2.5
3.0
3.5
4.0
4.5
5.0
Odds ratio
4 6 8 101214161820222426282
Wireless phone, latency (years)
F : Restricted cubic spline plot of the relationship between
latency of wireless phones and meningioma. e solid line indicates
theORestimateandthebrokenlinesrepresentthe%CI.
Adjustment was made for age at diagnosis, gender, socioeconomic
index (SEI), and year for diagnosis.
We divided cumulative use in hours of wireless phones
into quartiles. e results were based on , responding
glioma cases and , responding controls []. For both
mobile and cordless phones the highest risk was found in
BioMed Research International
T  : Specicity. Odds ratio (OR) and % condence interval (CI) for glioma (𝑛= ,) and meningioma cases (𝑛= ,) as the reference
entity. Numbers of exposed cases (Ca) and controls (Co) are given. Adjustment was made for age at diagnosis, gender, socioeconomic index
(SEI), and year for diagnosis [].
Ipsilateral Contralateral
Ca/Co OR % CI Ca/Co OR % CI
Analogue / . .–. / . .–.
Digital (G) / . .–. / . .–.
Digital (UMTS, G) / . .–. / . .–.
Mobile phone, total / . .–. / . .–.
Cordless phone / . .–. / . .–.
T  : Te m p o r a l i t y . Odds ratio (OR) and % condence interval (CI) for latency and glioma risk in three dierent case-control studies,
Interphone  (mobile phone) [], Coureau et al.  (mobile phone) [], and Hardell and Carlberg  (wireless phones) [].
All > y latency > y latency
Interphone (2010)
Mobile phone .
(.–.)
.
(.–.)
Coureau et al. (2014)
Mobile phone .
(.–.)
.
(.–.)
(i) Last decile of cumulative duration ( h)
(a)  y censorship .
(.–.)
(b)  y censorship .
(.–.)
Hardell and Carlberg (2015)
Wireless phone .
(.–.)
.
(.–.)
.
(.–.)
Mobile phone .
(.–.)
.
(.–.)
.
(.–.)
Regular use, –. y latency = OR ..
T  : Biological Gradient. Numbers of cases (Ca), controls (Co), and odds ratio (OR) with % condence interval (CI) for cumulative
use of mobile phone in hours and glioma risk in Interphone [].
Cumulative call time (hours) Ca/Co OR (% CI)
Never regular user ,/, (.)
< / . (.–.)
–. / . (.–.)
–. / . (.–.)
–. / . (.–.)
–. / . (.–.)
–. / . (.–.)
–. / . (.–.)
–. / . (.–.)
–,. / . (.–.)
, / . (.–.)
,/ . (.–.)
Regular use < h = OR . (ref).
thefourthquartilewithastatisticallysignicanttrend;see
Table .
3.6. Plausibility. One aspect on association or causality is if
the disease is biologically plausible. e IARC evaluation in
May  [, ] concluded that there is “limited evidence in
experimental animals for the carcinogenicity of radiofrequency
radiation”;seepage[].
Eects on tumour susceptibility in mice exposed to a
UMTS (universal mobile telecommunications system) test
BioMed Research International
T  : Biological Gradient. Numbers of cases (Ca), controls (Co), and odds ratio (OR) with % condence interval (CI) for cumulative
duration of calls (hours) in Coureau et al. [].
Cumulative duration of calls (hours) Ca/Co OR (% CI)
No use / (.)
< / . (.–.)
– / . (.–.)
– / . (.–.)
– / . (.–.)
 / . (.–.)
𝑝value global test .
T : Biological Gradient. Numbers of cases (Ca), controls (Co), and odds ratio (OR) with % condence interval (CI) for cumulative
duration of calls (hours) of wireless phones in quartiles in Hardell and Carlberg [].
Quartile
Mobile phone Cordless phone Wireless phone
OR, CI
(Ca/Co)
OR, CI
(Ca/Co)
OR, CI
(Ca/Co)
First quartile, all
.
.–.
(/)
.
.–.
(/)
.
.–.
(/)
Second quartile, all
.
.–.
(/)
.
.–.
(/)
.
.–.
(/)
ird quartile, all
.
.–.
(/)
.
.–.
(/)
.
.–.
(/)
Fourth quartile, all
.
.–.
(/)
.
.–.
(/)
.
.–.
(/)
𝑝,trend <. <. <.
Firstquartileh;secondquartileh;thirdquartile,h;fourthquartile>, h.
signal from fetal time for up to  months were studied by
Tillmann et al. []. Animals were exposed to UMTS
elds with intensities of , ., and W/m2.elow-
dose group, . W/m2, was subjected to additional prenatal
ethylnitrosourea (ENU) treatment. e ENU-treated group
and UMTS-exposed at . W/m2showed an increased lung
tumour rate and an increased incidence of lung carcinomas as
compared to the controls treated with ENU only. e authors
concluded that the study showed a cocarcinogenic eect of
lifelong UMTS exposure in female mice subjected to pre-
treatment with ENU. is study was included in the IARC
evaluation.
e results by Tillmann et al. [] gained further interest
based on the results in a follow-up study published in 
[]. e exposure levels were  (sham), ., ., and
 W/kg SAR. Numbers of tumours of the lungs and livers and
malignant lymphoma in exposed animals were statistically
signicant higher than in sham-exposed controls. A tumour-
promoting eect from RF radiation was found at low to mod-
erate levels (. and . W/kg SAR), well below exposure
limits for users of mobile phones [].
A report was released from e National Toxicology Pro-
gram (NTP) under the National Institutes of Health (NIH)
in USA on the largest ever animal study on cell phone RF
radiation and cancer []. An increased incidence of glioma
in the brain and malignant schwannoma in the heart was
found in rats. Acoustic neuroma or vestibular schwannoma
is a similar type of tumour as the one found in the heart,
although benign. ese results have gained considerable
interest since epidemiological human studies have in addition
to glioma also found an increased risk for acoustic neuroma,
also called vestibular schwannoma [].
Inastudypublishedinexposureto,MHzRF
radiation induced oxidative DNA base damage in a mouse
spermatocyte-derived cell line []. ere was a concomitant
increase in reactive oxygen species (ROS). is eect was mit-
igated by cotreatment with the antioxidant 𝛼-tocopherol. e
authors concluded that RF radiation with insucient energy
for the direct induction of DNA strand breaks can give
genotoxicity through oxidative DNA base damage.
Yakymenko et al. [] showed in a review of  studies
investigating oxidative eects of low-intensity RF radiation in
livingcellsthatexposuredownto,𝜇W/m2[] and
with SAR values down to  𝜇W/kg [, ] could increase
oxidativestressinthecells.Itshouldbenotedthatthe
guideline for mobile phone SAR is  W/kg. e  W/kg
guideline is in any  g of tissue while in the US (FCC
guideline) the exposure limit value is . W/kg in g of tissue.
 BioMed Research International
T  : Coherence. Hazard ratio (HR) and % condence interval (CI) for survival of patients with glioma and use of wireless phones,
study period – [].
Latency > years Glioma Glioblastoma multiforme
HR % CI HR % CI
Wireless phone . .–. . .–.
Mobile phone . .–. . .–.
Cordless phone . .–. . .–.
T  : Coherence. Hazard ratio (HR) and % condence interval (CI) for survival of patients with glioblastoma multiforme and use of
wireless phones in dierent age groups, study period – [].
Mobile phone Cordless phone Wireless phone
𝑛, exp HR % CI 𝑛,exp HR %CI 𝑛, exp HR % CI
Glioblastoma multiforme (𝑛=926)
Age, rst use
< years old  . .–. . .–.  . .–.
– years old  . .–.  . .–.  . .–.
 years old  . .–.  . .–.  . .–.
Certainly these results on oxidative stress are of concern since
ROS are of crucial importance in carcinogenesis.
3.7. Coherence. Hill points out that an association would be
strengthened if an exposure changes the biology and natural
history of the disease. One interesting gene is the p53 protein.
It is a transcription factor that plays a vital role in regulating
cell growth, DNA repair, and apoptosis, and p53 mutations
areinvolvedindiseaseprogression.Inastudyitwasfound
that use of mobile phones for  hours a day was associated
with increased risk for the mutant type of p53 gene expression
in the peripheral zone of glioblastoma multiforme, the most
malignant glioma type. Furthermore, this mutation increase
was statistically signicant correlated with shorter overall
survival time [].
We analyzed survival of , glioma patients in our
– and – case-control studies []. Use of
wireless phones in the > years’ latency group (time since
rst use) gave a reduced survival yielding hazard ratio (HR)
= ., % CI = .–. for glioma; see Table . For
glioblastoma multiforme (high-grade glioma; 𝑛 = 926)
mobile phone use yielded HR = ., % CI = .–.
andcordlessphoneuseHR=.,%CI=.in
thesamelatencycategory.ehazardratioforglioblastoma
multiforme increased statistically signicant per year of
latency for wireless phones, HR = ., % CI = .–.,
and of borderline statistical signicance per  h cumulative
use, HR = ., % CI = .–.. e hazard ratio was
highest in the age group < years for rst use of a wireless
phone; see Table .
In contrast for low-grade astrocytoma (grades I-II; 𝑛=
228) decreased HR (increased survival) was found for mobile
phone use HR = ., % CI = .–. and cordless phone
use HR = ., % CI = .–., and for wireless phones
in total statistically signicant decreased HR = ., % CI =
.–.. e reason for the survival benet for cases with
astrocytoma grades I-II associated with use of both mobile
andcordlessphonesisunclear.However,surgeryiscrucial
for survival in patients with low-grade astrocytoma that may
transform to high-grade glioma in the long term. An earlier
treatment gives a better prognosis. Tumour promotion from
RF radiation might give earlier symptoms leading to surgery.
For  (%) of the  cases with low-grade astrocytoma it
was possible to calculate tumour volume based on CT/MRI
scans []. is gave for cases exposed to wireless phones
(𝑛 = 121)medianvolume=.cm
3(mean = ., range
= .–.) compared with unexposed cases (𝑛=23)
median volume = . cm3(mean = ., range = .–.).
Although the dierence was not statistically signicant (p,
Wilcoxon rank-sum test = .), these results indicate tumour
promotion from RF radiation since the median tumour
volume was .% larger in exposed cases. is might cause
tumour awareness and earlier surgery.
Also for glioblastoma multiforme the median tumour
volume was larger in exposed cases (𝑛 = 346)thanin
unexposed cases (𝑛 = 112), . versus . cm3,that
is, .% larger volume, p,Wilcoxonrank-sumtest=.
[]. is tumour type is extremely malignant with median
survival in the range of  months in spite of surgery and
radio- and chemotherapy []. us early detection does not
signicantly change the prognosis.
It has been suggested that overall incidence data on brain
tumours for countries may be used to qualify or disqualify
theassociationbetweenmobilephonesandbraintumours
observed in case-control studies. During recent years such
opinions have been published by dierent study groups.
However, it must be stressed that descriptive epidemiology
with no individual exposure data is of less value than results in
analytical epidemiology such as case-control studies. Studies
should primarily be aimed at investigating incidence in
the most exposed part of the brain, the temporal lobe.
Of special interest is the incidence of the most malignant
glioma type, glioblastoma multiforme. We have discussed this
in previous publications, for example, [, ]. In England
BioMed Research International 
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
Glioblastoma multiforme age-standardized incidence rate
(UK Oce of National Statistics data for England)
All C71 primary
malignant tumours
All GBM
GBM other brain sites
GBM frontal and
temporal lobes
ASR ESP2013 Rate/100k people
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
F : Graphical data on age-standardized incidence rate of
glioblastoma multiforme in England –. Data provided by
Alasdair Philips. A detailed analysis is under publication.
increasing incidence of glioblastoma multiforme, especially
in the frontal and temporal lobes, during – has been
found; see Figure . Of interest is that a real increase in the
incidence of glioblastoma multiforme in frontal and temporal
lobes and cerebellum was reported in USA [].
No increasing incidence of brain tumours has been
recorded in the Swedish Cancer Register. We have discussed
themanyshortcomingsinthereportingofnewcaseselse-
where []. Using the Swedish Inpatient Register (IPR) we
foundanincreasingrateofpatientswithD=tumourof
unknowntypeinthebrainorCNSwithjoinpointin;
see Figure . A joinpoint was found in  for increasing
death rate of D in the Swedish Causes of Death Register,
Figure . No histopathology is available for these cases but
they may represent glioblastoma multiforme based on results
in IPR with joinpoint in  and the short survival for these
patients.
In an ecological study from England annual incidence
ofbraintumoursinthetemporalandparietallobeswas
modelledbasedonpopulation-levelcovariates.estudy
period was –. Malignant brain tumours in the
temporal lobe increased faster than would be expected. Using
a latency period of  years this increase was related to the
penetration of mobile phone use. is corresponded to an
additional increase of % (% credible interval %; %)
or  (% CI –) additional cases annually []. e
author concluded that the ndings were in agreement with
mobile phones and other wireless equipment being causing
factors.
3.8. Experiment. Sir Bradford Hill discussed in his paper
if prevention has an eect on the risk. Relating to wireless
phones no such community experiment exists. Antioxidants
such as melatonin, vitamin C, and vitamin E (𝛼-tocopherol)
may alleviate the generation of ROS [, ]. ere are
however no studies if persons taking antioxidants and using
wireless phones have a reduced risk for glioma.
12
10
8
6
4
2
0
1997 1999 2001 2003 2005
Year
2009 2011 20132007
Number of patients per 100,000
Inpatient care, D43, all: 1 joinpoint
Observed
1998–2007 APC = 0.17
2007–2013 APC = 4.25
F : Joinpoint regression analysis of number of patients per
, inhabitants according to the Swedish National Inpatient
Register for both genders combined, all ages during –
diagnosed with D = tumour of unknown type in the brain or CNS
[]. Statistically signicant trend.
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
Million minutes, mobile phones
Death rate, D43 (all)
Joinpoint regression, D43
0
5000
10000
15000
20000
25000
30000
Million minutes
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Death rate per 100,000
F : Number of outgoing mobile phone minutes in mil-
lions during – and joinpoint regression analysis of age-
standardized death rates per , inhabitants according to the
SwedishCausesofDeathRegisterforallagesduring
diagnosed with D = tumour of unknown type in the brain or CNS
[].
Mobile phones were introduced in Sweden in the early
s. First, it was very common to use the phone in a car with
external antenna without any use outside the car. In our rst
study period – a number of cases and controls had
only used the mobile phone in a car with external antenna.
In addition one control reported always use of a hands-free
 BioMed Research International
T : Analogy. Odds ratio (OR) and % condence interval (CI) for glioblastoma multiforme for occupational exposure to ELF-
EMF in time windows; – years and + years before diagnosis. Unconditional logistic regression, adjusted for age at diagnosis, gender,
socioeconomic index (SEI), and year of diagnosis. Exposure the year before diagnosis was excluded (“-year lag”). Numbers of exposed cases
(Ca) and controls (Co) are given [].
Cumulative exposure (𝜇T-year s) Glioblastoma multiforme (𝑛 = 687)
Ca/Co OR % CI
1–14 years’ time window
<. / .
.– <. / . .–.
.– <. / . .–.
.– <. / . .–.
.+ / . .–.
p, linear trend <.
15+ years’ time window
<. / .
.– <. / . .–.
.– <. / . .–.
.– <. / . .–.
.+ / . .–.
p, linear trend .
device []. ey were regarded as unexposed to RF radiation.
BraintumourriskinthisgroupwascalculatedtocrudeOR=
., % CI = .–..
3.9. Analogy. e last viewpoint by Bradford Hill is analogy.
Is there some evidence with another similar exposure? One
analogy would be glioma risk associated with extremely low-
frequency electromagnetic elds (ELF-EMF). In  IARC
classied ELF-EMF as “possibly carcinogenic to humans,”
Group B based on an increased risk for childhood leukemia
[]. More recently a pooled analysis showed about twofold
increased risk for childhood leukemia at exposure level above
.–. 𝜇T [], further supporting a carcinogenic potential
from ELF-EMF.
ELF-EMF is generated by alternating electric currency
and humans may be exposed both during leisure time and
in dierent occupational settings. In an evaluation of epi-
demiological ndings on exposure to ELF-EMF it was con-
cluded regarding glioma that an increased risk was seen in
electric and electronics industries [].
Based on occupational history it was possible to calculate
ELF-EMF job exposure for cases and controls using a job-
exposure matrix (JEM) both in Interphone [] and in our
studies [].
In the international Interphone study glioma was asso-
ciated with occupational ELF-EMF exposure in recent time
windows whereas no increased risk was found for menin-
gioma []. e authors concluded that such exposure may
playaroleinlatestagecarcinogenesisofglioma.
e results in our studies were based on , glioma
cases and , population based controls []. Cumulative
exposure (th percentile versus <th percentile) in-
creased the risk for glioblastoma multiforme in -year time
windows (data not in table) up to  years; see Table  for
time windows – and + years.
With longer latency periods (+ years) no statisti-
cally signicant increased risk and trend were found. For
low-grade glioma no statistically signicant increased risk
was seen in the dierent time windows. In conclusion
this study showed an increased risk in late stage (promo-
tion/progression) of glioblastoma multiforme for occupa-
tional ELF-EMF exposure.
4. Discussion
In this review we considered all nine viewpoints by Bradford
Hill on association or causation regarding use of wireless
phones and glioma risk. It is an update of our article from 
on this issue [] since more scientic evidence has emerged
since then. As discussed above aer the IARC evaluation in
 concluding RF radiation to be “possibly carcinogenic” to
humans several organizations have stated that the association
has been weaker or even no consistent evidence for an
increased risk for brain tumours. is has in part been based
on a much criticized Danish cohort study on persons with
mobile phone subscriptions and assumed mobile phone use
with funding from the telecom industry []. e study
was not based on sound epidemiological principles and had
several methodological limitations mainly due to poor expo-
sure assessment that render it to be uninformative at best [].
Some of the many shortcomings include the following.
() Corporate subscribers of mobile phones (,
people), which are likely to have been heavy users,
were classied as “unexposed.”
() Mobile phone subscription holders not using the
phone were classied as “exposed.”
() Users of cordless phones not using a mobile phone
were classied as “unexposed.”
BioMed Research International 
() Nonsubscribers using the mobile phone were classi-
ed as “unexposed.”
() Persons with a mobile phone subscription later than
 were classied as “unexposed.”
() No individual exposure data were assessed (e.g., on
cumulative exposure or side of head mostly used).
() No operator-veried data on years of subscription
were assessed.
ese limitations are likely to have led to an underes-
timate of any risk in this study. One would expect consid-
erable misclassication of mobile phone use both among
subscribers and the reference population since no new sub-
scribers were included in the exposed cohort aer . We
stated that “aer reviewing the four publications on the Danish
cohort study, one might rightly wonder whether this cohort was
initially set up to show no increased risk.A similar conclusion
was made by IARC in the  evaluation, thus stating that
using the “reliance on subscription to a mobile-phone provider,
asasurrogateformobilephoneuse,couldhaveresultedin
considerable misclassication in exposure assessment”[].e
Danish cohort study should no longer be cited as scientic
evidence on no increased risk for glioma among mobile
phone users.
A study in UK published in  has been included
in the no risk paradigm []. Use of mobile phones was
assessed in about % of a cohort of women established
for other purposes during –. Only baseline data
collectedatonetimebetweenandwereusedwith
the questions: “About how oen do you use a mobile phone?”
(never, less than once a day, every day) and “For how long have
you used one?” (total years of use). In , the participants
were asked how much they did talk on a mobile phone and
how many years they had used the phone. However, these
later data were not used in the analysis. Of those reporting no
useofamobilephoneatbaseline,%reportedsuchusein
. e incidence of brain tumours was assessed in 
and the average follow-up was only  years. No increased
incidence of glioma was found (𝑛 = 571 cases). For acoustic
neuroma (𝑛=96cases), there was an increase in risk with
long term use versus never use (+ years: relative risk (RR)
= ., % CI = .–., 𝑝= .), the risk increasing with
duration of use (trend among users, 𝑝= .). No data were
available on handedness for mobile phone use or tumour
localization in the brain. Use of cordless phones was ignored.
is study had poor assessment of exposure and has the
same shortcomings as the Danish cohort study. Benson et al.
gave in a letter to the Editor updated follow-up data to 
[]. ey found no longer a statistically signicant increased
risk for acoustic neuroma. However, these results were based
on the same baseline data as previously and similarly lack
scientic precision in the assessment of exposure. Due to the
many shortcomings this study should not be cited as evidence
of no increased risk for glioma among mobile phone users.
Not all are careful in the evaluation of scientic evidence
on RF radiation and glioma risk. Repacholi et al. in their
article published on line  included the Danish cohort
study in the review on glioma risk []. ey stated that
they included also cordless phone use although no results
were presented from the German part of Interphone claimed
to have assessed cordless phone use. We have found in our
studies a consistent increased glioma risk associated with
use of cordless phones []. However, Repacholi et al. stated
that “most of the studies from the Hardell group report an
association whereas other studies do not. e reason for this is
unclear.” One reason is that the other studies like Interphone
didnotreportuseofcordlessphonesthusdiminishingthe
risk towards unity []. In fact, the results in the Hardell
group studies are similar to Interphone and Coureau et al.;
seeTables,,,and.Repacholietal.consideredtheHill
viewpoints thereby excluding some of the viewpoints and
modifying others. ey concluded that “in summary, none of
the Hill criteria support a causal relationship between wireless
phone use and brain cancers or other tumors in the areas of
the head that most absorb the RF energy from wireless phones.
Accordingly, the conclusions and recommendations of WHO
[2011]provideadequateprotectivemeasures,andtheICNIRP
guidelines limiting exposure to RF elds [ICNIRP, 1998, 2009b]
continue to provide a sound, science-based standard for public
health policy regarding the use of wireless phones by adults.”
Obviously this conclusion is not based on an understanding
and thorough evaluation of Hill’s viewpoints. At best it
might be an example of misunderstanding scientic evidence
withoutbasicknowledgeinpathologyandoncology.e
practice to misuse Hill’s viewpoints (misinterpreted as criteria
for causation) has been discussed by Kundi [].
In contrast to the Repacholi et al. publication [] we have
used the original Hill viewpoints without modication or
exclusions.atwouldgiveamoredecentandtrueevaluation
basedontheseviewpoints.Regardingstrength Hill wrote
that “we must not be too ready to dismiss a cause-and-eect
hypothesis merely on the ground that the observed association
appears to be slight.” Our analysis showed doubled risk
for glioma in the group with highest cumulative exposure;
seeTable.ussimilarresultswerefoundindierent
populations by dierent study groups.
Regarding consistency, Bradford Hill wrote that the
observed association has been “repeatedly observed by dier-
ent persons, in dierent places, circumstances and times.” As
canbeseeninTableconsistencywasfoundnotonlyfor
cumulative use but also for latency.
Specicity is a “strong argument in favour of causation
according to Hill. Ipsilateral exposure to RF radiation in
the temporal lobe is the area with highest exposure to RF
radiation. ere is a consistent nding of increased risk
foruseofthewirelessphoneonthesamesideasthe
tumour occurred. is risk is conrmed in analysis of glioma
risk in the temporal lobe, and also using distance to the
mobile phone and estimated total cumulative specic energy
in J/kg []. Furthermore the risk is specic for glioma using
meningioma cases as the comparison group in the same study
[].
e temporal relationship of the association is important.
us, exposure should precede the disease outcome. In
carcinogenesis also latency (time from exposure to glioma
diagnosis) is of relevance. Clearly OR increased with latency
in the case-control studies with highest risk in the + group
 BioMed Research International
[]. e maximum latency was shorter in Interphone [] and
Coureau et al. [] but still yielded highest risk.
Abiological gradient,dose-response,shouldbefound.In
the case-control studies a statistically signicant trend with
increasing call time in hours was reported by Coureau et
al.[]andinourstudy[].InInterphoneastatistically
signicant increased risk was only found in the th decile
of cumulative use , hours. Also restricting the analysis
tosubjectswithregularmobilephoneusegavehighestrisk
inthesamegroup,OR=.,%CI=...Notrend
analysis was reported; see Appendix 2[]. In the alternative
post hoc matching of cases and controls in Interphone
(closest in age and time for interview) the th decile of
cumulativeusegaveOR=.,%CI=..[].
For plausibility Hill stated that “it will be helpful if the
causation we suspect is biologically plausible. But this is a
feature I am convinced we cannot demand. What is biologically
plausible depends upon the biological knowledge of the day.
By now there are studies showing a cocarcinogenic and
tumour-promoting eect from RF radiation. One postulated
mechanism would be generation of ROS that can give base-
pair damage of DNA. ese eects have been shown in several
experimental studies with RF radiation levels well below
current guideline for exposure during use of mobile phones.
For coherence thenaturalhistoryandbiologyofthe
disease are evaluated. One interesting aspect is the increased
risk for the mutant type of the p53 geneexpressioninglioblas-
toma multiforme associated with use of mobile phones [].
e mutation is involved in disease progression and shorter
survival was found in patients with the mutant gene. is
nding is of large interest in relation to our result showing
shorter survival in patients using mobile or cordless phones
[]. e age group < years for rst use of the wireless
phonehadthehighesthazardratio,thatis,thestrongest
reduction in survival. e tumour volume was larger in
glioma cases using wireless phones compared with nonusers.
It should also be noted that 𝛼was higher in larger glioma
tumours with shortest distance from preferred ear to tumour
center which might be an eect of tumour promotion [].
Several studies have shown an increasing incidence of glioma,
especially glioblastoma multiforme in the temporal lobe.
esefactsshowachangeinthenaturalhistoryofthedisease.
Itisdiculttoperformanexperiment for a rare disease
like glioma. us, the risk would be studied among persons
that have stopped use of wireless phones and analyze a
possible risk reduction over time as seen for lung cancer
risk in ex-smokers. Such a cohort study is in practice almost
impossible to perform, especially for a rare disease like
brain tumour. Some indirect evidence might be found by
the nding in our study that use of mobile phone in a
car with external antenna and no other use of a wireless
phone(noexposuretoRFradiation)gavenoincreasedbrain
tumour risk []. is nding, as well as the alleviation of
ROS production from RF radiation by antioxidants, might be
proxies for experiment.
e last viewpoint by Hill is analogy.Isthereglioma
risk with similar exposure? ELF-EMF has been classied as
possibly human carcinogen,GroupBbyIARCin[].
Based on occupational ELF-EMF exposure an increased risk
for glioma has now been found in two case-control studies
[, ].
5. Conclusion
e nine Bradford Hill viewpoints on association or causation
regarding RF radiation and glioma risk seem to be fullled 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.
Disclosure
e funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the
manuscript.
Competing Interests
e authors declare that there is no conict of interests
regarding the publication of this paper.
Authors’ Contributions
Both authors have read and approved the nal manuscript.
Acknowledgments
e study was supported by grants from Mr. Brian Stein,
Cancer-och Allergifonden, Cancerhj¨
alpen, and Pandora-
Foundation for Independent Research, Berlin, Germany.
References
[] A. B. Hill, “e environment and disease: association or cau-
sation?” JournaloftheRoyalSocietyofMedicine,vol.,no.,
pp. –, .
[] Interphone Study Group, “Brain tumour risk in relation to
mobile telephone use: results of the INTERPHONE interna-
tional case-control study,International Journal of Epidemiol-
ogy,vol.,pp.,.
[] R. Saracci and J. Samet, “Commentary: call me on my mobile
phone...or better not?—a look at the INTERPHONE study
results,” International Journal of Epidemiology,vol.,no.,pp.
–, .
[] R.Baan,Y.Grosse,B.Lauby-Secretanetal.,“Carcinogenicityof
radiofrequency electromagnetic elds,e Lancet Oncology,
vol.,no.,pp.,.
[] IARC Monographs on the Evaluation of Carcinogenic Risks
to Humans, Non-Ionizing Radiation, Part 2: Radiofrequency
Electromagnetic Fields, vol. , International Agency for
Research on Cancer, Lyon, France, , http://monographs
.iarc.fr/ENG/Monographs/vol/mono.pdf.
[] L. Hardell, ˚
A. N¨
asman, A. P˚
ahlson,A.Hallquist,andK.
Hansson Mild, “Use of cellular telephones and the risk for
brain tumours: A Case-control Study,International Journal of
Oncology,vol.,no.,pp.,.
[]L.Hardell,K.HanssonMild,A.P
˚
ahlson, and A. Hallquist,
“Ionizing radiation, cellular telephones and the risk for brain
BioMed Research International 
tumours,European Journal of Cancer Prevention,vol.,no.,
pp. –, .
[]L.Hardell,A.Hallquist,K.HanssonMild,M.Carlberg,A.
P˚
ahlson, and A. Lilja, “Cellular and cordless telephones and the
risk for brain tumours,European Journal of Cancer Prevention,
vol. , no. , pp. –, .
[] L.Hardell,K.HanssonMild,andM.Carlberg,“Furtheraspects
on cellular and cordless telephones and brain tumours,Inter-
national Journal of Oncology,vol.,no.,pp.,.
[] L. Hardell, M. Carlberg, and K. Hansson Mild, “Pooled analysis
of two case-control studies on use of cellular and cordless
telephones and the risk for malignant brain tumours diagnosed
in –,International Archives of Occupational and Envi-
ronmental Health,vol.,no.,pp.,.
[] L. Hardell, M. Carlberg, and K. Hansson Mild, “Pooled analysis
of two case-control studies on the use of cellular and cordless
telephones and the risk of benign brain tumours diagnosed
during –,International Journal of Oncology,vol.,
no. , pp. –, .
[] L. Hardell, M. Carlberg, and K. Hansson Mild, “Mobile phone
use and the risk for malignant brain tumors: a case-control
study on deceased cases and controls,Neuroepidemiology,vol.
,no.,pp.,.
[] L. Hardell, M. Carlberg, and K. Hansson Mild, “Pooled analysis
of case-control studies on malignant brain tumours and the use
of mobile and cordless phones including living and deceased
subjects,International Journal of Oncology,vol.,no.,pp.
–, .
[] Interphone Study Group, “Acoustic neuroma risk in relation to
mobile telephone use: results of the INTERPHONE interna-
tional case-control study,Cancer Epidemiology,vol.,pp.
–, .
[] E. Cardis, B. K. Armstrong, J. D. Bowman et al., “Risk of
brain tumours in relation to estimated RF dose from mobile
phones: results from ve interphone countries,Occupational
and Environmental Medicine,vol.,no.,pp.,.
[] E. K. Ong and S. A. Glantz, “Tobacco industry eorts subverting
International Agency for Research on Cancers second-hand
smoke study,e Lancet,vol.,no.,pp.,.
[] D. Michaels, Doubt is eir Product. How Industry’s Assault on
Science reatens Your Health,OxfordUniversityPress,New
Yo r k , N Y, U S A ,     .
[] T.O.McGarityandW.E.Wagner,Bending Science. How Special
Interests Corrupt Public Health Research,HarvardUniversity
Press, London, UK, .
[] N. Oreskes and E. M. Conway, Merchants of Doubt: How a
Handful of Scientists Obscured the Truth on Issues from Tobacco
Smoke to Global Warming,BloomsburyPress,NewYork,NY,
USA, .
[] M. J. Walker, Ed., Corporate Ties that Bind. An Examination
of Corporate Manipulation and Vested Interest in Public Health,
Skyhorse Publishing, New York, NY, USA, .
[] World Health Organization, “Electromagnetic elds and
public health: mobile phones,” Fact Sheet no. , ,
http://www.who.int/mediacentre/factsheets/fs/en/.
[] A. J. Swerdlow, M. Feychting, A. C. Green, L. Kheifets, and D. A.
Savitz,“Mobilephones,braintumors,andtheinterphonestudy:
where are we now?” EnvironmentalHealthPerspectives,vol.,
no. , pp. –, .
[] M. H. Repacholi, A. Lerchl, M. R¨
o¨
osli et al., “Systematic review
of wireless phone use and brain cancer and other head tumors,
Bioelectromagnetics,vol.,no.,pp.,.
[] International Commission on Non-Ionizing Radiation Protec-
tion, “Guidelines for limiting exposure to time-varying electric,
magnetic, and electromagnetic elds (up to  GHz),Health
Physics,vol.,pp.,.
[] International Commission on Non-Ionizing Radiation Protec-
tion, “ICNIRP statement on the ‘guidelines for limiting expo-
sure to time-varying electric, magnetic and electromagnetic
elds (up to  GHz)’, Health Physics,vol.,pp.,
.
[] C.SageandD.O.Carpenter,Eds.,BioInitiative Working Group:
BioInitiative Report: A Rationale for a Biologically-based Public
Exposure Standard for Electromagnetic Fields (ELF and RF), Bio-
initiative,  http://www.bioinitiative.org/table-of-contents/.
[] BioInitiative Working Group: BioInitiative, ARationalefora
Biologically-Based Public Exposure Standard for Electromagnetic
Fields (ELF and RF),EditedbyC.SageandD.O.Carpenter,Bio-
initiative, , http://www.bioinitiative.org/table-of-contents/.
[] L. Hedendahl, M. Carlberg, and L. Hardell, “Electromagnetic
hypersensitivity-an increasing challenge to the medical profes-
sion,Reviews on Environmental Health,vol.,no.,pp.
, .
[] Health Protection Agency, Health Eects from Radiofrequency
Electromagnetic Fields. Report of the Independent Advisory
Group on Non-Ionising Radiation, Documents of the Health
Protection Agency. Radiation, Chemical and Environmental
Hazards, , http://webarchive.nationalarchives.gov.uk/
/http://www.hpa.org.uk/webc/HPAwebFile/
HPAweb_C/.
[] Nordic radiation safety authorities. Exposure from mobile
phones, base stations and wireless networks. A statement by
the Nordic radiation safety authorities, , http://www.nrpa
.no/dav/ce.pdf.
[] Health Canada, “Fact Sheet—What is Safety Code ? Environ-
mental and Workplace Health,”  http://www.hc-sc.gc.ca/
ewh-semt/pubs/radiation/radio_guide-lignes_direct/safety_code
__fs-code_securite__fr-eng.php.
[] e Institution of Engineering and Technology, Do Low-Level
Electromagnetic Fields up to 300 GHz Harm Us?,  , http://www
.theiet.org/factles/bioeects/emf-position-page.cfm?type=pdf.
[] Scientic Committee on Emerging Newly Identied Health
Risks, “Opinion on potential health eects of exposure to
electromagnetic elds (EMF),” European Commission, ,
http://ec.europa.eu/health/scientic_committees/emerging/docs/
scenihr_o_.pdf.
[] Swedish Radiation Safety Authority [Str˚
als¨
akerhetsmyn-
digheten],“RecentResearchonEMFandHealthRisk-Tenth
report from SSM’s Scientic Council on Electromagnetic
Fields,”  http://www.stralsakerhetsmyndigheten.se/Global/
Publikationer/Rapport/Stralskydd/  /S SM -Rapport- -.pdf.
[] Health Council of the Netherlands, “Mobile phones and cancer.
Part . Update and overall conclusions from epidemiologi-
cal and animal studies,”  https://ww w.gezondheidsraad.nl/
sites/default/les/_mobilephonescancerpart.pdf.
[] Swedish Radiation Safety Authority [Str˚
als¨
akerhetsmyn-
digheten], “Recent Research on EMF and Health Risk-Eleventh
report from SSM’s Scientic Council on Electromagnetic
Fields, . Including irteen years of electromagnetic
eld research monitored by SSM’s Scientic Council on EMF
and health: How has the evidence changed over time?” 
http://www.stralsakerhetsmyndigheten.se/Global/Publikationer/
Rapport/Stralskydd//SSM_Rapport___webb_.pdf.
 BioMed Research International
[] L. Hardell and M. Carlberg, “Using the Hill viewpoints from
 for evaluating strengths of evidence of the risk for brain
tumors associated with use of mobile and cordless phones,
Reviews on Environmental Health,vol.,no.-,pp.,
.
[] L. Hardell and M. Carlberg, “Mobile phone and cordless phone
use and the risk for glioma—analysis of pooled case-control
studies in Sweden, – and –,Pathophysiology,
vol.,no.,pp.,.
[] G. Coureau, G. Bouvier, P. Lebailly et al., “Mobile phone use
and brain tumours in the CERENAT case-control study,Occu-
pational and Environmental Medicine,vol.,no.,pp.,
.
[] M. C. Turner, S. Sadetzki, C. E. Langer et al., “Investigation of
bias related to dierences between case and control interview
dates in ve INTERPHONE countries,Annals of Epidemiology,
vol. , no. , pp. .e–.e, .
[] D. Aydin, M. Feychting, J. Sch¨
uz et al., “Mobile phone use and
brain tumors in children and adolescents: a multicenter case-
control study,Journal of the National Cancer Institute,vol.,
no. , pp. –, .
[] L. Hardell, M. Carlberg, and K. Hansson Mild, “Re-analysis of
riskforgliomainrelationtomobiletelephoneuse:Comparison
with the results of the Interphone international case-control
study,International Journal of Epidemiology,vol.,no.,pp.
–, .
[] E.Cardis,I.Deltour,S.Mannetal.,“DistributionofRFenergy
emitted by mobile phones in anatomical structures of the brain,
Physics in Medicine and Biology,vol.,no.,pp.,
.
[] K. Grell, K. Frederiksen, J. Sch¨
uz et al., “e intracranial
distribution of gliomas in relation to exposure from mobile
phones: analyses from the INTERPHONE study,American
Journal of Epidemiology,vol.,no.,pp.,.
[] T. Tillmann, H. Ernst, J. Streckert et al., “Indication of cocar-
cinogenic potential of chronic UMTS-modulated radiofre-
quency exposure in an ethylnitrosourea mouse model,Inter-
national Journal of Radiation Biology,vol.,no.,pp.,
.
[]A.Lerchl,M.Klose,K.Groteetal.,“Tumorpromotionby
exposure to radiofrequency electromagnetic elds below expo-
sure limits for humans,Biochemical and Biophysical Research
Communications,vol.,no.,pp.,.
[] M. Wyde, M. Cesta, C. Blystone et al., “Report of Partial
Findings from the National Toxicology Program Carcinogen-
esis Studies of Cell Phone Radiofrequency Radiation in Hsd:
Sprague DawleySD rats (Whole Body Exposures),” Dra -
-. US National Toxicology Program (NTP),  http://
biorxiv.org/content/biorxiv/early////.full.pdf.
[] L. Hardell, M. Carlberg, F. S¨
oderqvist, and K. Hansson Mild,
“Pooled analysis of case-control studies on acoustic neuroma
diagnosed – and – and use of mobile and
cordless phones,International Journal of Oncology,vol.,no.
, pp. –, .
[] C.Liu,W.Duan,S.Xuetal.,“ExposuretoMHzradiofre-
quency electromagnetic radiation induces oxidative DNA base
damage in a mouse spermatocyte-derived cell line,Tox i c o l og y
Letters,vol.,no.,pp.,.
[] I. Yakymenko, O. Tsybulin, E. Sidorik, D. Henshel, O.
Kyrylenko, and S. Kyrylenko, “Oxidative mechanisms of biolog-
ical activity of low-intensity radiofrequency radiation,Electro-
magnetic Biology and Medicine,vol.,no.,pp.,.
[] A. Burlaka, O. Tsybulin, E. Sidorik et al., “Overproduction of
free radical species in embryonal cells exposed to low intensity
radiofrequency radiation,Experimental Oncology,vol.,no.,
pp.,.
[] K.Megha,P.S.Deshmukh,B.D.Banerjee,A.K.Tripathi,and
M. P. Abegaonkar, “Microwave radiation induced oxidative
stress, cognitive impairment and inammation in brain of
Fischer rats,Indian Journal of Experimental Biology,vol.,no.
, pp. –, .
[] K. Megha, P. S. Deshmukh, B. D. Banerjee, A. K. Tripathi, R.
Ahmed,and M. P. Abegaonkar, “Low intensity microwave
radiation induced oxidative stress, inammatory response and
DNAdamageinratbrain,NeuroToxicology,vol.,pp.,
.
[]R.Akhavan-Sigari,M.M.F.Baf,V.Ariabod,V.Rohde,and
S. Rahighi, “Connection between cell phone use, p gene
expression in dierent zones of glioblastoma multiforme and
survival prognoses,Rare Tumors,vol.,no.,articleno.,
.
[] M. Carlberg and L. Hardell, “Decreased survival of glioma
patients with astrocytoma grade IV (glioblastoma multiforme)
associated with long-term use of mobile and cordless phones,
International Journal of Environmental Research and Public
Health,vol.,no.,pp.,.
[] F.T.VertosickJr.,R.G.Selker,andV.C.Arena,“Survivalof
patients with well-dierentiated astrocytomas diagnosed in the
era of computed tomography,Neurosurgery,vol.,no.,pp.
–, .
[] L. Hardell and M. Carlberg, “Mobile and cordless phone use
and brain tumor risk,” in Bioelectromagnetic and Subtle Energy
Medicine,P.J.Rosch,Ed.,CRCPress,BocaRaton,Fla,USA,
.
[] G. Zada, A. E. Bond, Y.-P. Wang, S. L. Giannotta, and D.
Deapen, “Incidence trends in the anatomic location of primary
malignant brain tumors in the United States: –,Worl d
Neurosurgery,vol.,no.-,pp.,.
[] L. Hardell and M. Carlberg, “Increasing rates of brain tumours
in the Swedish National Inpatient Register and the Causes
of Death Register,International Journal of Environmental
Research and Public Health,vol.,no.,pp.,.
[] F. de Vocht, “Inferring the – impact of mobile phone
use on selected brain cancer subtypes using Bayesian structural
time series and synthetic controls,Environment International,
vol. , pp. –, .
[] F. Ozguner, Y. Bardak, and S. Comlekci, “Protective eects of
melatonin and caeic acid phenethyl ester against retinal oxida-
tive stress in long-term use of mobile phone: a comparative
study,Molecular and Cellular Biochemistry,vol.,no.-,pp.
–, .
[]WorldHealthOrganizationInternationalAgencyforRe-
search on Cancer, IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans, Volume 80. Non-Ionizing Radi-
ation, Part I: Static and Extremely Low-Frequency (ELF) Elec-
tric and Magnetic Fields,IARCPress,Lyon,France,,
http://monographs.iarc.f r/ENG/Monographs /vol /mono. pdf.
[] L. Kheifets, A. Ahlbom, C. M. Crespi et al., “Pooled analysis
of recent studies on magnetic elds and childhood leukaemia,
British Journal of Cancer,vol.,no.,pp.,.
[] L.Hardell,B.Holmberg,H.Malker,andL.-E.Paulsson,“Expo-
sure to extremely low frequency electromagnetic elds and the
risk of malignant diseases—an evaluation of epidemiological
BioMed Research International 
and experimental ndings,European Journal of Cancer Preven-
tion,vol.,no.,pp.,.
[]M.C.Turner,G.Benke,J.D.Bowmanetal.,“Occupational
exposure to extremely low-frequency magnetic elds and brain
tumor risks in the INTEROCC study,Cancer Epidemiology
Biomarkers and Prevention,vol.,no.,pp.,.
[]M.Carlberg,T.Koppel,M.Ahonen,andL.Hardell,“Case-
control study on occupational exposure to extremely low-
frequency electromagnetic elds and glioma risk,American
Journal of Industrial Medicine,Inpress.
[] M. Kundi, “Failure to detect a link between mobile phone use
and brain tumours in a large Danish cohort study: but ndings
may be due to bias,Ev idence-Based Medicine,vol.,no.,pp.
–, .
[] F. S¨
oderqvist, M. Carlberg, and L. Hardell, “Review of four
publications on the Danish cohort study on mobile phone
subscribers and risk of brain tumors,Re views on Environmental
Health,vol.,no.,pp.,.
[] V.S.Benson,K.Pirie,J.Sch
¨
uz,G.K.Reeves,V.Beral,andJ.
Green, “Mobile phone use and risk of brain neoplasms and
other cancers: prospective study,International Journal of Epi-
demiology,vol.,pp.,.
[] V.S.Benson,K.Pirie,J.Sch
¨
uz,G.K.Reeves,V.Beral,andJ.
Green, “Authors’ response to: the case of acoustic neuroma:
comment on mobile phone use and risk of brain neoplasms and
other cancers,International Journal of Epidemiology,vol.,no.
, article no. , .
[] L. Hardell, M. Carlberg, and K. Hansson Mild, “Methodological
aspects of epidemiological studies on the use of mobile phones
and their association with brain tumors,Open Environmental
Sciences,vol.,pp.,.
[] M. Kundi, “Causality and the interpretation of epidemiologic
evidence,EnvironmentalHealthPerspectives,vol.,no.,pp.
–, .
... During the past 15 years, epidemiological studies have found an increasing association between mobile or cordless phone use and brain tumors in humans (86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98). Moreover, during the past 20 years, statistical studies have found associations between exposure to MT base station antennas and devices, and reported symptoms of un-wellness referred to as 'microwave syndrome' or 'electro-hypersensitivity' (EHS). ...
... It is documented that both such types of human-made EMF-exposure can induce OS (3,34,(36)(37)(38)(39)43,45,109), DNA damage 84,85) and infertility (56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71). It is also documented that the same types of EMF-exposure are linked with increased cancer risk both in humans and experimental animals (72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(110)(111)(112)(113)(114). ...
Article
Full-text available
Exposure of animals/biological samples to human‑made electromagnetic fields (EMFs), especially in the extremely low frequency (ELF) band, and the microwave/radio frequency (RF) band which is always combined with ELF, may lead to DNA damage. DNA damage is connected with cell death, infertility and other pathologies, including cancer. ELF exposure from high‑voltage power lines and complex RF exposure from wireless communication antennas/devices are linked to increased cancer risk. Almost all human‑made RF EMFs include ELF components in the form of modulation, pulsing and random variability. Thus, in addition to polarization and coherence, the existence of ELFs is a common feature of almost all human‑made EMFs. The present study reviews the DNA damage and related effects induced by human‑made EMFs. The ion forced‑oscillation mechanism for irregular gating of voltage‑gated ion channels on cell membranes by polarized/coherent EMFs is extensively described. Dysfunction of ion channels disrupts intracellular ionic concentrations, which determine the cell's electrochemical balance and homeostasis. The present study shows how this can result in DNA damage through reactive oxygen species/free radical overproduction. Thus, a complete picture is provided of how human‑made EMF exposure may indeed lead to DNA damage and related pathologies, including cancer. Moreover, it is suggested that the non‑thermal biological effects attributed to RF EMFs are actually due to their ELF components.
... In 2015, the Swedish team and 13 other countries reported significant risks associated with gliomas from exposure to electromagnetic radiation, which was reclassified by the International Agency for Research on Cancer (IARC) from group 2B (probable) to Group 2A (highest level) (38,39). Researchers found that mobile phone users had an eightfold increased risk of brain tumors among people exposed to electromagnetic radiation in cities (40,41). ...
Article
Full-text available
Purpose: Although classical techniques for image segmentation may work well for some images, they may perform poorly or not work at all for others. It often depends on the properties of the particular image segmentation task under study. The reliable segmentation of brain tumors in medical images represents a particularly challenging and essential task. For example, some brain tumors may exhibit complex so-called "bottle-neck" shapes which are essentially circles with long indistinct tapering tails, known as a "dual tail." Such challenging conditions may not be readily segmented, particularly in the extended tail region or around the so-called "bottle-neck" area. In those cases, existing image segmentation techniques often fail to work well. Methods: Existing research on image segmentation using wormhole and entangle theory is first analyzed. Next, a random positioning search method that uses a quantum-behaved particle swarm optimization (QPSO) approach is improved by using a hyperbolic wormhole path measure for seeding and linking particles. Finally, our novel quantum and wormhole-behaved particle swarm optimization (QWPSO) is proposed. Results: Experimental results show that our QWPSO algorithm can better cluster complex "dual tail" regions into groupings with greater adaptability than conventional QPSO. Experimental work also improves operational efficiency and segmentation accuracy compared with current competing reference methods. Conclusion: Our QWPSO method appears extremely promising for isolating smeared/indistinct regions of complex shape typical of medical image segmentation tasks. The technique is especially advantageous for segmentation in the so-called "bottle-neck" and "dual tail"-shaped regions appearing in brain tumor images.
... The image shape characteristic of a glioma is an unclear contour with, at best, a visible cystic or ring enhancement (20). According to recent animal studies, along with limited epidemiological evidence, radiofrequency radiation leads to an increased risk of brain glioma, especially in the case of mobile phone addiction or long-term cell phone use (21). It is because radiation with low energy can influence the wave frequency of electrons outside the nucleus and the binding force between particles, such as atoms and ions (22). ...
Article
Full-text available
Background The input image of a blurry glioma image segmentation is, usually, very unclear. It is difficult to obtain the accurate contour line of image segmentation. The main challenge facing the researchers is to correctly determine the area where the points on the contour line belong to the glioma image. This article highlights the mechanism of formation of glioma and provides an image segmentation prediction model to assist in the accurate division of glioma contour points. The proposed prediction model of segmentation associated with the process of the formation of glioma is innovative and challenging. Bose-Einstein Condensate (BEC) is a microscopic quantum phenomenon in which atoms condense to the ground state of energy as the temperature approaches absolute zero. In this article, we propose a BEC kernel function and a novel prediction model based on the BEC kernel to detect the relationship between the process of the BEC and the formation of a brain glioma. Furthermore, the theoretical derivation and proof of the prediction model are given from micro to macro through quantum mechanics, wave, oscillation of glioma, and statistical distribution of laws. The prediction model is a distinct segmentation model that is guided by BEC theory for blurry glioma image segmentation. Results Our approach is based on five tests. The first three tests aimed at confirming the measuring range of T and μ in the BEC kernel. The results are extended from −10 to 10, approximating the standard range to T ≤ 0, and μ from 0 to 6.7. Tests 4 and 5 are comparison tests. The comparison in Test 4 was based on various established cluster methods. The results show that our prediction model in image evaluation parameters of P, R, and F is the best amongst all the existent ten forms except for only one reference with the mean value of F that is between 0.88 and 0.93, while our approach returns between 0.85 and 0.99. Test 5 aimed to further compare our results, especially with CNN (Convolutional Neural Networks) methods, by challenging Brain Tumor Segmentation (BraTS) and clinic patient datasets. Our results were also better than all reference tests. In addition, the proposed prediction model with the BEC kernel is feasible and has a comparative validity in glioma image segmentation. Conclusions Theoretical derivation and experimental verification show that the prediction model based on the BEC kernel can solve the problem of accurate segmentation of blurry glioma images. It demonstrates that the BEC kernel is a more feasible, valid, and accurate approach than a lot of the recent year segmentation methods. It is also an advanced and innovative model of prediction deducing from micro BEC theory to macro glioma image segmentation.
... Because they are so widespread and in such constant use, the possible physiological effects of non-thermal emanations from cellular phones and Wi-Fi on the human body have generated concern [3][4][5] and given rise to a large literature including on the physiological consequences in the brain and nervous system; in the reproductive system including sperm formation; in the onset of cancers; and in many other health-related conditions (for recent reviews see e.g. [6][7][8][9]). However, given the wide range of experimental protocols and signal parameters used in the different studies, as well as frequently contradictory results, many of these effects remain controversial and poorly resolved. ...
Article
Full-text available
The modern telecommunications industry is ubiquitous throughout the world, with a significant percentage of the population using cellular phones on a daily basis. The possible physiological consequences of wireless emissions in the GHz range are therefore of major interest, but remain poorly understood. Here, we show that exposure to a 1.8 GHz carrier frequency in the amplitude range of household telecommunications induces the formation of ROS (Reactive Oxygen Species) in human HEK293 cultured cells. The ROS concentrations detected by fluorescent imaging techniques increased significantly after 15 minutes of RF field exposure, and were localized to both nuclear and cytosolic cellular compartments. qPCR analysis showed altered gene expression of both anti-oxidative (SOD, GPX, GPX, and CAT) and oxidative (Nox-2) enzymes. In addition, multiple genes previously identified as responsive to static magnetic fields were found to also be regulated by RF, suggesting common features in response mechanisms. By contrast, many RF effects showed evidence of hormesis, whereby biological responsivity does not occur linearly as a function of signal amplitude. Instead, biphasic dose response curves occur with 'blind' spots at certain signal amplitudes where no measureable response occurs. We conclude that modulation of intracellular ROS can be a direct consequence of RF exposure dependent on signal frequency and amplitude. Since changes in intracellular ROS may have both harmful and beneficial effects, these could provide the basis for many reported physiological effects of RF exposure.