VOLUME 27 NUMBER 33 NOVEMBER 20 2009

JOURNAL OF CLINICAL ONCOLOGY

O R I G I N A L

R E P O R T

Mobile Phone Use and Risk of Tumors: A Meta-Analysis

Seung-Kwon Myung, Woong Ju, Diana D. McDonnell, Yeon Ji Lee, Gene Kazinets, Chih-Tao Cheng,
and Joel M. Moskowitz
From the Smoking Cessation Clinic,
Center for Cancer Prevention and
Detection; Division of Cancer Prevention, National Cancer Control
Research Institute, National Cancer
Center, Goyang; Department of
Obstetrics and Gynecology, School of
Medicine, Ewha Womans University;
Department of Family Medicine,
Seoul National University Hospital,
Seoul, Republic of Korea; and Center
for Family and Community Health,
School of Public Health, University of
California, Berkeley, Berkeley, CA.
Submitted December 19, 2008;
accepted June 9, 2009; published
online ahead of print at www.jco.org on
October 13, 2009.
Written on behalf of the Korean MetaAnalysis (KORMA) Study Group.
Supported in part by the Centers for
Disease Control and Prevention through
Cooperative Agreement No.
U48/DP000033 (D.D.M., G.K., J.M.M.).
The contents of the article are solely
the responsibility of the authors and do
not necessarily represent the official
views of the Centers for Disease
Control and Prevention.
Authors disclosures of potential conflicts of interest and author contributions are found at the end of this
article.
Corresponding author: Seung-Kwon
Myung, MD, MS, 111 Jungbalsan-ro,
Ilsandong-gu, Goyang, Gyeonggi-do,
410-769, Republic of Korea; e-mail:
msk@ncc.re.kr.
The Appendix is included in the
full-text version of this article,
available online at www.jco.org.
It is not included in the PDF version
(via Adobe Reader).
2009 by American Society of Clinical
Oncology
0732-183X/09/2733-5565/$20.00
DOI: 10.1200/JCO.2008.21.6366

Purpose
Case-control studies have reported inconsistent findings regarding the association between
mobile phone use and tumor risk. We investigated these associations using a meta-analysis.
Methods
We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in August 2008. Two
evaluators independently reviewed and selected articles based on predetermined selection criteria.
Results
Of 465 articles meeting our initial criteria, 23 case-control studies, which involved 37,916
participants (12,344 patient cases and 25,572 controls), were included in the final analyses.
Compared with never or rarely having used a mobile phone, the odds ratio for overall use was 0.98
for malignant and benign tumors (95% CI, 0.89 to 1.07) in a random-effects meta-analysis of all 23
studies. However, a significant positive association (harmful effect) was observed in a randomeffects meta-analysis of eight studies using blinding, whereas a significant negative association
(protective effect) was observed in a fixed-effects meta-analysis of 15 studies not using blinding.
Mobile phone use of 10 years or longer was associated with a risk of tumors in 13 studies
reporting this association (odds ratio 1.18; 95% CI, 1.04 to 1.34). Further, these findings were
also observed in the subgroup analyses by methodologic quality of study. Blinding and methodologic quality of study were strongly associated with the research group.
Conclusion
The current study found that there is possible evidence linking mobile phone use to an increased
risk of tumors from a meta-analysis of low-biased case-control studies. Prospective cohort studies
providing a higher level of evidence are needed.
J Clin Oncol 27:5565-5572. 2009 by American Society of Clinical Oncology

INTRODUCTION

The worldwide use of mobile phones has rapidly

increased over the past decade. According to data
from the International Telecommunication Union,
the number of worldwide mobile cellular subscribers was 12.2 per 100 inhabitants in 2000 but
grew to 49.5 per 100 inhabitants in 2007.1 With
the increasing use of mobile phones (ie, cellular
phones and cordless phones), concern has been
raised about the possible carcinogenic effects as a
result of exposure to radiofrequency electromagnetic fields (EMFs) emitted from cellular phones
ranging from 800 to 2,000 MHz,2,3 which fall in
the microwave spectrum. Although some in vitro
studies reported the potential effects of highfrequency EMFs on cell proliferation and activation of oncogene transcription,4-6 those biologic
effects and mechanisms in developing neoplasm remain unclear. Over the past decade, epide-

miologic studies (mainly case-control) also have

reported the relationships between the use of mobile
phones and malignant or benign tumors such as brain
tumors, head and neck tumors, non-Hodgkins lymphoma, and testicular cancer.7-28
Some case-control studies have suggested a positive (ie, harmful) association between the use of mobile phones and the risk of tumors,7,10-12,15-18,23,25,27
whereas other case-control studies have reported no
significant association.8,9,11,13,14,19-22,24,26,28 Also, the
only retrospective cohort study reported no evidence for the association among either short-term
or long-term users.29,30
Regarding the conflicting scientific evidence,
three meta-analyses reported no association or a
slight increased risk.31-33 However, these metaanalyses involved only brain tumors. In the current
study, we investigated the associations between the
use of mobile phones and the risk of tumors, including both malignant and benign conditions, via a
meta-analysis of case-control studies.
2009 by American Society of Clinical Oncology

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5565

Myung et al

METHODS
Literature Search
We searched MEDLINE (PubMed; 1968 to August 2008), EMBASE
(1977 to August 2008), and the Cochrane Central Register of Controlled Trials
(CENTRAL) in the Cochrane Library (1953 to August 2008) using common
keywords related to mobile phones and tumor or cancer. The keywords were
as follows: mobile phones, cellular phones, or cordless phones and
tumors or cancer. We also reviewed the bibliographies of relevant
articles to locate additional publications. The language of publication was
not restricted.
Selection Criteria
We included epidemiologic studies that met all of the following criteria:
case-control study (to date, no randomized controlled trials and only one
retrospective cohort study published in four different articles have been reported; therefore, we included only case-control studies in this study); investigated the associations between the use of mobile phones, cellular phones, or
cordless phones and malignant or benign tumors; reported outcome measures
with adjusted odds ratios and 95% CIs, crude odds ratios and 95% CIs, or
values in cells of a 2 2 table (from which odds ratios could be calculated). If
data were duplicated or shared in more than one study, the first published or
more comprehensive study was included in the analysis.
Selection of Relevant Studies
Two of the authors (S.-K.M. and W.J.) independently evaluated eligibility of all studies retrieved from the databases based on the predetermined
selection criteria. Disagreements between evaluators were resolved by discussion or in consultation with a third author (D.D.M.).
Assessment of Methodologic Quality
We assessed the methodologic quality of included studies based on the
Newcastle-Ottawa Scale (NOS) for quality of case-control studies in metaanalyses.34 A star system of the NOS (range, 0 to 9 stars) has been developed for
the assessment. In the current study, we considered a study awarded 7 or more
stars as a high-quality study because standard criteria have not been established. The mean value for the 23 studies assessed was 6.3 stars.
Main and Subgroup Analyses
We investigated the association between the use of mobile phones (use v
never or rarely use, if possible) and the overall risk of all tumors by using
adjusted data as a main analysis. We also performed subgroup analyses by
whether the status of patient cases and controls was blinded at interview
(blinded or not blinded/no description), research group (adjusted or crude
data), methodologic quality (high or low quality), type of tumor, malignancy
of tumor (malignant or benign), type of mobile phone (analog or digital),
laterality of tumor (ipsilateral or contralateral), and type of case-control study
(hospital based or population based). Furthermore, we investigated the association between long-term mobile phone use ( 10 years) and the risk of
tumors, including subgroup analyses by the factors listed earlier.
Statistical Analyses
To compute a pooled odds ratio with 95% CI, we used the adjusted odds
ratio and 95% CIs reported in each article whenever possible. We examined
heterogeneity in results across studies using Higgins I2, which measures the
percentage of total variation across studies.35 We considered an I2 value of
greater than 50% as indicative of substantial heterogeneity.
When substantial heterogeneity was not observed, the pooled estimate
calculated based on the fixed-effects model was reported using the Woolfs
(inverse variance) method. When substantial heterogeneity was observed, the
pooled estimate calculated based on the random-effects model was reported
using the DerSimonian and Laird method.36
We evaluated publication bias of the studies included in the final analysis
using Beggs funnel plot and Eggers test. If publication bias exists, Beggs
funnel plot is asymmetric or the P value is less than .05 by Eggers test. Also, a
meta-regression analysis was performed to assess the effect of subgroups and
study characteristics, such as research group, year of publication, type of
tumor, and study design, on the study results. Blinding and methodologic
5566

2009 by American Society of Clinical Oncology

quality were excluded because of multicollinearity with research group. We

used Stata SE version 10.0 software package (StataCorp, College Station, TX)
for statistical analysis.

RESULTS

Identification of Relevant Studies

Figure 1 shows a flow diagram of how we identified relevant
studies. A total of 465 articles were identified by searching three databases and hand-searching relevant bibliographies. We excluded 135
duplicate articles and an additional 287 articles that did not satisfy the
selection criteria. After reviewing the full texts of the remaining 43
articles, 21 articles37-57 were excluded because of several reasons, as
shown in Figure 1. The remaining 23 case-control studies from 22
articles7-28 were included in the final analysis (the study by Auvinen et
al11 was considered as two individual case-control studies).
Characteristics of Studies Included in the
Final Analysis
In the 23 case-control studies, we identified a total of 37,916
participants (12,344 patient cases and 25,572 controls). For studies
reporting age and sex, the mean age was 52.6 years (range, 18 to 90
years), and 51% of the participants were women.
Appendix Table A1 (online only) shows the general characteristics of the 23 case-control studies (22 articles) included in the final
analysis. The percentage of study participants who reported having
used a mobile phone was 43.5% among the patient cases and 45.2%
among the controls (data not shown in Appendix Table A1).

Identified studies from the databases using keywords and bibliographies of

relevant articles (N = 465):
PubMed (n = 255), EMBASE (n = 183), Cochrane Library (n = 25),
and bibliographies (n = 2)

Exclude duplicate articles (n = 135)

Articles remaining after excluding duplicates (n = 330)

Exclude according to selection criteria (n = 287)

Remaining articles (n = 43), full text review

Excluded articles (n = 21):

Shared an identical population (n = 8)
Included totally or partly in another article (n = 10)
Letter, comments, or correspondence (n = 3)

23 case-control studies among 22 articles* included in the final analysis

Fig 1. Flow diagram for identification of relevant case-control studies. (*) One
article (Auvinen et al11) was divided into two studies because it involved two
different types of tumors.
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Meta-Analysis of Mobile Phone Use and Risk of Tumor

Study

OR (95% CI)

Studies using blinding (n = 8)

Hardell et al (1999)
Stang et al (2001)
Hardell et al (2002)
Hardell et al (2004)
Hardell et al (2005, I)
Hardell et al (2005, N)
Hardell et al (2006)
Hardell et al (2007)
Subtotal (I2 = 54.7%)

Weight (%)

0.98 (0.69 to 1.41)

2.80 (1.00 to 7.90)
1.15 (0.99 to 1.33)
1.02 (0.75 to 1.38)
1.06 (0.87 to 1.31)
1.40 (1.03 to 1.90)
1.90 (1.30 to 2.70)
1.00 (0.80 to 1.20)
1.17 (1.02 to 1.36)

3.74
0.72
7.04
4.42
6.03
4.40
3.65
6.07
36.08

0.85 (0.60 to 1.20)

0.90 (0.70 to 1.10)
1.30 (0.90 to 1.80)
1.30 (0.40 to 4.70)
0.60 (0.20 to 1.90)
0.90 (0.70 to 1.10)
1.00 (0.70 to 1.30)
0.80 (0.54 to 1.20)
0.91 (0.75 to 1.11)
0.73 (0.43 to 1.23)
0.93 (0.69 to 1.27)
0.78 (0.68 to 0.91)
0.76 (0.65 to 0.89)
0.87 (0.68 to 1.13)
0.87 (0.63 to 1.22)
0.85 (0.80 to 0.91)

3.87
5.66
3.87
0.52
0.62
5.66
4.36
3.28
6.18
2.26
4.42
7.07
6.88
5.19
4.07
63.92

0.98 (0.89 to 1.07)

100.00

Studies not using blinding (n = 15)

Muscat et al (2000)
Inskip et al (2001)
Auvinen et al (2002, A)
Auvinen et al (2002, B)
Warren et al (2003)
Schoemaker et al (2005)
Linet et al (2006)
Lonn et al (2006)
Schuz et al (2006)
Takebayashi et al (2006)
Hours et al (2007)
Lahkola et al (2007)
Lahkola et al (2008)
Sadetzki et al (2008)
Takebayashi et al (2008)
Subtotal (I2 = 0.0%)
Heterogeneity between groups: P < .001
Overall (I2 = 59.7%)

.2

.5

Overall Use of Mobile Phones and Risk of Tumors

As shown in Figure 2, the overall use of mobile phones (use v
never or rarely use) was not significantly associated with the risk of
tumors in a random-effects model meta-analysis of all 23 case-control
studies (odds ratio 0.98; 95% CI, 0.89 to 1.07). However, a significant positive association (ie, harmful effect) was observed in eight
studies 7,12,14-16,18,23 and one study by another group10) using blinding
(odds ratio 1.17; 95% CI, 1.02 to 1.36), whereas a significant negative association (ie, protective effect) was observed in 15 studies (nine
INTERPHONE-related studies17,20-22,24-28 and six studies by other
groups8,9,11,13,19) not using blinding (odds ratio 0.85; 95% CI, 0.80
to 0.91). No publication bias was observed in the selected studies
(Beggs funnel plot was symmetric; Eggers test, P for bias .21; Fig 3).

log OR

-1

Eggers test: P for bias = .21

-2
0

.2

.4

.6

Standard error of log OR

Fig 3. Beggs funnel plots and Eggers test for identifying publication bias
(P .21) in a meta-analysis of case-control studies7-28 (n 23). OR, odds ratio.
www.jco.org

Fig 2. Overall use of mobile phones and

the risk of tumors in a random-effects
model meta-analysis of case-control
studies7-28 by the use of blinding at an
interview for exposure measurements
(n 23). OR, odds ratio; Hardell et al
(2005, I) indicates reference 15; Hardell et
al (2005, N) indicates reference 16.

Table 1 shows the methodologic quality of studies included in the

final analysis. The range of quality scores was 5 to 8; the average score
was 6.3. The high-quality studies (score of 7) included all seven of
the studies by Hardell et al, one INTERPHONE-related study, and two
studies by other groups. The low-quality studies (score of 7) included eight INTERPHONE-related studies and six studies by
other groups.
A subgroup meta-analysis by research group showed a significant
positive association for the seven studies reported by Hardell et al but
a significant negative association for nine INTERPHONE-related
studies (Table 2). When using crude data, a significant association was
not found in any of the 23 studies or in subgroup analyses by research group.
Subgroup meta-analyses by methodologic quality of study revealed a significant positive association in the high-quality studies
(odds ratio 1.09; 95% CI, 1.01 to 1.18), whereas a negative association was observed in the low-quality studies. In subgroup metaanalyses by malignancy of tumor, no significant association was
observed for malignant tumors. However, a significant negative association was observed for benign tumors. Neither the use of analog
phones nor the use of digital phones was associated with the risk of
tumors. The ipsilateral use of mobile phones (ie, on the same side of
the head where the tumor exists) was marginally associated with the
risk of tumors in the 12 studies reporting tumor laterality.
Mobile Phone Use of 10 Years or Longer and Risk
of Tumors
Among the 23 studies, there was a significant positive association between mobile phone use of 10 years or longer and the risk
of tumors in a fixed-effects meta-analysis of 13 studies reporting
this association (odds ratio 1.18; 95% CI, 1.04 to 1.34; Fig 4;
Appendix Table A2, online only). As for blinding, a fixed-effects
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Myung et al

Table 1. Methodologic Quality of Studies Included in the Final Analysis Based on the Newcastle-Ottawa Scale for Assessing the Quality of Case-Control Studies

Study
Hardell et al7
Muscat et al8
Inskip et al9
Stang et al10 (hospital based)
Stang et al10 (population
based)
Auvinen et al11 (1)
Auvinen et al11 (2)
Hardell et al12
Warren et al13
Hardell et al14
Hardell et al15
Hardell et al16
Schoemaker et al17
Hardell et al18
Linet et al19
Lnn et al20
Schz et al21
Takebayashi et al22
Hardell et al23
Hours et al24
Lahkola et al25
Lahkola et al26
Sadetzki et al27
Takebayashi et al28

Selection (score)

Comparability
(score)

Adequate
Definition
of Patient Representativeness Selection
Definition
Cases
of Patient Cases
of Controls of Controls

Control for
Important
Factor or
Additional
Factor

Exposure (score)
Same Method
of
Ascertainment Ascertainment
of Exposure
for
Nonresponse Total
Score
(blinding)
Participants
Rate

1
1
1
1

1
0
0
1

1
0
0
0

0
1
1
0

1
2
2
2

1
0
0
1

1
1
1
1

1
0
0
0

7
5
5
6

1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1

1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1

1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1

0
1
1
0
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
0

2
1
1
2
1
1
2
2
2
2
2
2
2
2
2
2
2
1
1
2

1
0
0
1
0
1
1
1
0
1
0
0
0
0
1
0
0
0
0
0

1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1

0
0
0
0
0
1
1
0
0
1
0
0
0
0
1
0
0
0
0
0

7
6
6
7
5
7
8
7
7
8
7
6
6
6
8
6
6
5
5
6

When there was no significant difference in the response rate between both groups by using a 2 test (P .05), one point was awarded.
Total score could range from 0 to 9 points.

meta-analysis of the seven blinded studies showed a positive association, whereas a fixed-effects meta-analysis of the six unblinded
studies showed no significant association.
In the subgroup meta-analyses by methodologic quality, a significant positive association was found in the eight high-quality studies
but not in the seven low-quality studies. With regard to tumor malignancy, mobile phone use of 10 years or longer was significantly positively associated with the risk of benign tumors but not with the risk of
malignant tumors.
The use of analog phones for 10 years or longer was positively
associated with the risk of tumors. However, further subgroup analyses by research group showed a significant association only in the
studies by Hardell et al.7,12,14-16,18,23 Regarding the laterality of tumors
and mobile phone use of 10 years or longer, a significantly increased
odds ratio was identified for ipsilateral use but not for contralateral use.
Overall Mobile Phone Use and the Risk of
Brain Tumors
As shown in Appendix Table A3 (online only), no significant
association was observed in a meta-analysis of 15 studies involving
brain tumors. For meningiomas, a preventive effect was observed,
and this effect was largely a result of a decreased odds ratio in
INTERPHONE-related studies.
5568

2009 by American Society of Clinical Oncology

A significant negative association was found in a meta-analysis of

studies involving benign brain tumors, and this was largely a result of
a decreased odds ratio in the INTERPHONE-related studies. No association between mobile phone use and tumor risk was observed in
both analog phone users and digital phone users. With regard to
research group, blinding, and methodologic quality, similar findings
to those of the subgroup analyses were observed (ie, a significant
association in the studies by Hardell et al, a negative association in
INTERPHONE-related studies, and no association in the studies by
other groups).
Overall Mobile Phone Use and the Risk of
Other Tumors
Appendix Table A4 (online only) shows the findings of the subgroup analyses of studies involving tumors other than brain tumors.
Unlike brain tumors, all of the subgroup meta-analyses based on
various factors showed no significant associations between overall
mobile phone use and the risk of other tumors.
Meta-Regression Analysis
A meta-regression analysis showed that only the variable indicating research group was significantly associated with the study results
(P .001). No significant association was observed for year of publication, type of tumor, or study design.
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Meta-Analysis of Mobile Phone Use and Risk of Tumor

Table 2. Mobile Phone Use (v never or rarely use) and the Risk of Tumors in Subgroup Meta-Analyses
Factor

No. of Studies

Summary OR

95% CI of OR

Heterogeneity, I2 (%)

Model Used

All
Research group
Hardell et al
INTERPHONE
Other groups
Research group (crude data)
Hardell et al
INTERPHONE
Other groups
Methodologic quality
High (low bias: 7 points)
Hardell et al
INTERPHONE
Other group
Low (high bias: 7 points)
INTERPHONE
Other groups
Malignancy of tumor
Malignant
Hardell et al
INTERPHONE
Other groups
Benign
Hardell et al
INTERPHONE
Other groups
Type of mobile phone
Analog
Hardell et al
INTERPHONE
Other groups
Digital
Hardell et al
INTERPHONE
Other groups
Laterality of tumor
Ipsilateral
Hardell et al
INTERPHONE
Contralateral
Hardell et al
INTERPHONE
Type of case-control study
Hospital based (all other groups)
Population based
Hardell et al
INTERPHONE
Other groups

23

0.98

0.89 to 1.07

59.7

Random effects

7
9
7
23
7
9
7

1.15
0.83
0.99
0.97
1.14
0.88
0.90

1.01 to 1.32
0.77 to 0.89
0.86 to 1.14
0.87 to 1.08
0.96 to 1.35
0.75 to 1.03
0.79 to 1.03

52.1
0
30.6
73.6
71.0
79.8
22.6

Random effects
Fixed effects
Fixed effects
Random effects
Random effects
Random effects
Fixed effects

10
7
1
2
14
8
6

1.09
1.15
0.90
1.02
0.85
0.82
0.97

1.01 to 1.18
1.00 to 1.32
0.70 to 1.10
0.75 to 1.38
0.79 to 0.91
0.76 to 0.88
0.83 to 1.14

46.3
52.1
NA
0
5.7
0
24.2

Fixed effects
Random effects
NA
Fixed effects
Fixed effects
Fixed effects
Fixed effects

15
6
4
5
15
4
8
3

1.00
1.11
0.78
0.97
0.87
1.17
0.81
0.82

0.89 to 1.13
0.96 to 1.29
0.67 to 0.91
0.80 to 1.18
0.80 to 0.95
0.97 to 1.42
0.73 to 0.90
0.61 to 1.11

52.0
50.5
0
19.6
20.7
3.8
0
0

Random effects
Random effects
Fixed effects
Fixed effects
Fixed effects
Fixed effects
Fixed effects
Fixed effects

12
7
3
2
14
7
5
2

0.96
1.04
0.84
1.55
0.95
1.10
0.78
0.93

0.87 to 1.07
0.89 to 1.22
0.72 to 0.96
1.08 to 2.2
0.84 to 1.08
0.97 to 1.24
0.71 to 0.85
0.55 to 1.59

49.9
34.5
0
0
55.8
12.7
0
0

Fixed effects
Fixed effects
Fixed effects
Fixed effects
Random effects
Fixed effects
Fixed effects
Fixed effects

12
4
8
11
3
8

1.22
1.80
1.00
0.94
1.31
0.81

0.99 to 1.51
1.24 to 2.62
0.91 to 1.10
0.77 to 1.15
0.74 to 2.31
0.74 to 0.89

85.9
84.9
37.0
82.3
93.0
48.2

Random effects
Random effects
Fixed effects
Random effects
Random effects
Fixed effects

4
20
7
9
4

0.89
0.99
1.15
0.83
1.14

0.74 to 1.07
0.89 to 1.09
1.01 to 1.32
0.77 to 0.89
0.91 to 1.43

0.0
61.8
52.1
0
0

Fixed effects
Random effects
Random effects
Fixed effects
Fixed effects

Abbreviations: OR, odds ratio; NA, not applicable.

Statistically significant positive association.

Statistically significant negative association.

DISCUSSION

We found that the use of mobile phones was associated with a mild
increased risk of tumors, when compared with never or rare use of
mobile phones, in the meta-analyses of case-control studies that used
blinding or had a high methodologic quality, whereas no significant
association was observed in a meta-analysis of all included studies.
www.jco.org

Also, mobile phone use of 10 years or longer increased the risk of

tumors in a meta-analysis of all the studies reporting this association.
Furthermore, in the subgroup meta-analyses by research group, a
distinct pattern of the findings was observed as follows: a positive
association (ie, harmful effect) in the Hardell et al studies, a negative
association (ie, protective effect) in the INTERPHONE-related studies, and no association in other research groups studies.
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Myung et al

Study

OR (95% CI)

Weight (%)

Studies using blinding (n = 7)

Hardell et al (1999)
Hardell et al (2002)
Hardell et al (2004)
Hardell et al (2005, I)
Hardell et al (2005, N)
Hardell et al (2006)
Hardell et al (2007)
Subtotal (I2 = 35.1%)

1.20 (0.56 to 2.59)

1.36 (0.83 to 2.22)
0.65 (0.27 to 1.59)
1.01 (0.72 to 1.42)
1.40 (0.99 to 1.98)
1.84 (1.34 to 2.53)
1.50 (0.60 to 3.70)
1.35 (1.14 to 1.59)

2.77
6.72
2.07
14.10
13.53
16.10
1.96
57.25

Studies not using blinding (n = 6)

Schoemaker et al (2005)
Lonn et al (2006)
Schuz et al (2006)
Lahkola et al (2007)
Lahkola et al (2008)
Sadetzki et al (2008)
Subtotal (I2 = 0.0%)

1.10 (0.70 to 1.80)

0.92 (0.33 to 2.56)
1.71 (0.87 to 3.37)
0.94 (0.69 to 1.28)
0.85 (0.57 to 1.26)
1.00 (0.48 to 2.09)
0.99 (0.82 to 1.21)

7.29
1.55
3.55
17.03
10.33
3.00
42.75

1.18 (1.04 to 1.34)

100.00

Heterogeneity between groups: P = .021

Overall (I2 = 33.1%)

.2

.5

These findings were strongly related to the fact that all of the
studies by Hardell et al used blinding to the status of patient cases or
controls at the interview and were categorized as having a high methodologic quality when assessed based on the NOS, whereas most of the
INTERPHONE-related studies and studies by other groups did not
use blinding and were thus categorized as having low methodologic
quality. The blinding item is one of the eight items in the NOS.
Nevertheless, we also used the blinding item independently as well as
the NOS as a kind of indicator of the quality assessment for the studies
because the NOS has not been fully validated and the blinding item
was considered an important factor that affects the findings of
each study.
Also, similar findings concerning the research group were observed in subgroup analyses by malignancy of tumor, type of laterality,
type of case-control study, and type of tumor. Regarding type of brain
tumor, a negative association was observed for meningiomas but not
for gliomas and acoustic neuromas, and this negative association
was largely a result of a decreased odds ratio in INTERPHONErelated studies.
Besides blinding and methodologic quality of studies, we should
consider two potential biases regarding the differences we found by
research groupsrecall bias and selection bias, both of which have
been described in detail elsewhere.57 In a validation study of shortterm recall for mobile phone use, Vrijheid et al58 reported that substantial random errors could reduce the power of the INTERPHONE
study to detect an increased risk of brain and parotid gland tumors.
Furthermore, they found that random errors and selection bias could
lead to finding a decreased risk of brain cancer through Monte-Carlo
simulation using the INTERPHONE data.57 These findings may explain why a significant decreased risk for tumor was observed among
mobile phone users in the INTERPHONE-related studies.
To reduce recall and selection biases, a prospective cohort
study is needed. A large nationwide Danish retrospective cohort
study,29,30,59,60 which is the only cohort study published so far, re5570

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Fig 4. Mobile phone use of 10 years or

longer and the risk of tumors in a fixedeffects model meta-analysis of casecontrol studies7,12,14-18,20,21,23,25-27 by
the use of blinding at an interview for
exposure measurements (n 13). OR,
odds ratio; Hardell et al (2005, I) indicates
reference 15; Hardell et al (2005, N) indicates reference 16.

ported that there was no evidence for an association between cellular

telephone use and tumor risk based on standardized incidence ratios
for cancer that were calculated from the cancer prevalence among
cellular telephone subscribers compared with the rates expected
among the general population. However, this study relied on phone
subscription information and did not evaluate actual exposure to
mobile phones.
If we do not consider subgroup meta-analyses by research group
or blinding/methodologic quality of studies, our overall results are
similar to the previous three meta-analyses31-33 evaluating mobile
phone use and the risk of brain tumor, which reported no overall
increased risk of brain tumors among cellular phone users and slightly
increased risk of brain tumors for use of 10 years or longer.
Unlike the previous meta-analyses, however, we found significant associations between mobile phone use and risk of tumors in
low-biased, case-control studies, which were mostly studies by Hardell
et al, when performing subgroup analyses by use of blinding or the
methodologic quality of studies. That is, the methodologic quality of
study and blinding were strongly related to both the research group
and the studies findings. In particular, among the items of the NOS
for assessing the quality of case-control studies, blinding and response
rates between patient cases and controls were the major contributing
factors to differentiate a high-quality study from a low-quality study.
All seven studies by Hardell et al7,12,14-16,18,23 used blinding, and five of
them showed no significant difference in response rates between patient cases and controls, whereas INTERPHONE-related studies and
the other studies, except for the study by Stang et al,10 did not use
blinding and showed a significant difference in response rates.
We feel the need to mention the funding sources for each research group because it is possible that these may have influenced the
respective study designs and results. According to the acknowledgments that appeared in the publications, the Hardell et al group was
supported by grants from the Swedish Work Environment Fund,
Orebro Cancer Fund, Orebro University Hospital Cancer Fund, and
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Meta-Analysis of Mobile Phone Use and Risk of Tumor

so on. Most of the INTERPHONE-related studies were mainly supported by the Quality of Life and Management of Living Resources
program of the European Union and the International Union Against
Cancer; the International Union Against Cancer received funds for
those studies from the Mobile Manufacturers Forum and the Global
System for Mobile Communication Association.
The association between mobile phone use and tumor risk also
remains unresolved in experimental studies using in vivo animal
models or in vitro cancer cell lines. Although it has been established
that low-frequency EMF (microwave) exposure induces biologic
change of cytoplasmic membranes, nuclear levels, and specific gene
levels,6,61-63 the effect of high-frequency EMF exposure on health is
still controversial.64-70
Our study has several limitations. First, it does not provide the
highest level of evidence because only case-control studies were involved. As mentioned previously, recall bias and selection bias might
reduce the quality of mobile phone exposure data and, therefore, cause
a spurious association. Second, we did not explore potential confounding factors in the studies by Hardell et al7,12,14-16,18,23 that reported positive results not found by other study groups. Those issues
need to be explored in future studies.
In sum, in our meta-analyses of case-control studies, we found
evidence linking mobile phone use to an increased risk of tumors,
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AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
The author(s) indicated no potential conflicts of interest.

AUTHOR CONTRIBUTIONS
Conception and design: Seung-Kwon Myung, Woong Ju
Administrative support: Seung-Kwon Myung, Woong Ju
Provision of study materials or patients: Seung-Kwon Myung
Collection and assembly of data: Seung-Kwon Myung, Woong Ju,
Diana D. McDonnell, Yeon Ji Lee, Gene Kazinets, Chih-Tao Cheng
Data analysis and interpretation: Seung-Kwon Myung, Woong Ju,
Diana D. McDonnell, Yeon Ji Lee, Gene Kazinets, Chih-Tao Cheng,
Joel M. Moskowitz
Manuscript writing: Seung-Kwon Myung, Diana D. McDonnell,
Joel M. Moskowitz
Final approval of manuscript: Seung-Kwon Myung

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