• Embed Doc
  • Copy Link
  • Readcast
  • Collections
  • CommentGo Back
Download
 
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 andDetection; Division of Cancer Preven-tion, National Cancer ControlResearch Institute, National CancerCenter, Goyang; Department ofObstetrics and Gynecology, School ofMedicine, Ewha Womans University;Department of Family Medicine,Seoul National University Hospital,Seoul, Republic of Korea; and Centerfor Family and Community Health,School of Public Health, University ofCalifornia, Berkeley, Berkeley, CA.Submitted December 19, 2008;accepted June 9, 2009; publishedonline ahead of print at www.jco.org onOctober 13, 2009.Written on behalf of the Korean Meta-Analysis (KORMA) Study Group.Supported in part by the Centers forDisease Control and Prevention throughCooperative Agreement No.U48/DP000033 (D.D.M., G.K., J.M.M.).The contents of the article are solelythe responsibility of the authors and donot necessarily represent the officialviews of the Centers for DiseaseControl and Prevention.Authors’ disclosures of potential con-flicts of interest and author contribu-tions are found at the end of thisarticle.Corresponding author: Seung-KwonMyung, MD, MS, 111 Jungbalsan-ro,Ilsandong-gu, Goyang, Gyeonggi-do,410-769, Republic of Korea; e-mail:msk@ncc.re.kr.© 2009 by American Society of ClinicalOncology0732-183X/09/2799-1/$20.00DOI: 10.1200/JCO.2008.21.6366
A B S T R A C T
Purpose
Case-control studies have reported inconsistent findings regarding the association betweenmobile 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. Twoevaluators independently reviewed and selected articles based on predetermined selection criteria.
Results
Of 465 articles meeting our initial criteria, 23 case-control studies, which involved 37,916participants (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 0.98for malignant and benign tumors (95% CI, 0.89 to 1.07) in a random-effects meta-analysis of all 23studies. However, a significant positive association (harmful effect) was observed in a random-effects 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 studiesreporting this association (odds ratio
1.18; 95% CI, 1.04 to 1.34). Further, these findings werealso observed in the subgroup analyses by methodologic quality of study. Blinding and method-ologic 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 increasedrisk of tumors from a meta-analysis of low-biased case-control studies. Prospective cohort studiesproviding a higher level of evidence are needed.
J Clin Oncol 27. © 2009 by American Society of Clinical Oncology 
INTRODUCTION
The worldwide use of mobile phones has rapidly increased over the past decade. According to datafrom the International Telecommunication Union,the number of worldwide mobile cellular sub-scribers was 12.2 per 100 inhabitants in 2000 butgrew to 49.5 per 100 inhabitants in 2007.
1
Withthe increasing use of mobile phones (ie, cellularphones and cordless phones), concern has beenraised about the possible carcinogenic effects as aresult of exposure to radiofrequency electromag-netic fields (EMFs) emitted from cellular phonesranging from 800 to 2,000 MHz,
2,3
which fall inthe microwave spectrum. Although some in vitrostudies reported the potential effects of high-frequency EMFs on cell proliferation and activa-tion of oncogene transcription,
4-6
those biologiceffects and mechanisms in developing neo-plasm remain unclear. Overthepastdecade,epide-miologic studies (mainly case-control) also havereported the relationships between the use of mobilephonesandmalignantorbenigntumorssuchasbraintumors, head and neck tumors, non-Hodgkin’s lym-phoma,andtesticularcancer.
7-28
Somecase-controlstudieshavesuggestedaposi-tive(ie,harmful)associationbetween the use of mo-bilephonesandtheriskoftumors,
7,10-12,15-18,23,25,27
whereasothercase-controlstudieshavereportednosignificantassociation.
8,9,11,13,14,19-22,24,26,28
Also,theonly retrospective cohort study reported no evi-dence for the association among either short-termorlong-termusers.
29,30
Regarding the conflicting scientific evidence,three meta-analyses reported no association or aslight increased risk.
31-33
However, these meta-analyses involved only brain tumors. In the currentstudy, we investigated the associations between theuseofmobilephonesandtheriskoftumors,includ-ing both malignant and benign conditions, via ameta-analysisofcase-controlstudies.
 J
OURNAL OF
C
LINICAL
O
NCOLOGY
O R I G I N A L R E P O R T
© 2009 by American Society of Clinical Oncology
1
 
http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2008.21.6366The latest version is at Published Ahead ofPrint on October 13, 2009 as 10.1200/JCO.2008.21.6366
 
Copyright 2009 by American Society of Clinical Oncology
Copyright © 2009 by the American Society of Clinical Oncology. All rights reserved.Information downloaded from jco.ascopubs.org and provided by National Cancer Center on October 13, 2009 from .
 
METHODS
Literature Search 
We searched MEDLINE (PubMed; 1968 to August 2008), EMBASE(1977toAugust2008),andtheCochraneCentralRegisterofControlledTrials(CENTRAL) in the Cochrane Library (1953 to August 2008) using commonkeywords related to mobile phones and tumor or cancer. The keywords wereas follows: “mobile phones,” “cellular phones,” or “cordless phones” and“tumors” or “cancer.” We also reviewed the bibliographies of relevantarticles to locate additional publications. The language of publication wasnot restricted.
Selection Criteria
Weincludedepidemiologicstudiesthatmetallofthefollowingcriteria:case-control study (to date, no randomized controlled trials and only oneretrospective cohort study published in four different articles have been re-ported; therefore, we included only case-control studies in this study); inves-tigatedtheassociationsbetweentheuseofmobilephones,cellularphones,orcordlessphonesandmalignantorbenigntumors;reportedoutcomemeasureswith adjusted odds ratios and 95% CIs, crude odds ratios and 95% CIs, orvaluesincellsofa2
2table(fromwhichoddsratioscouldbecalculated).If data were duplicated or shared in more than one study, the first published ormorecomprehensivestudywasincludedintheanalysis.
Selection of Relevant Studies 
Twooftheauthors(S.-K.M.andW.J.)independentlyevaluatedeligibil-ity of all studies retrieved from the databases based on the predeterminedselection criteria. Disagreements between evaluators were resolved by discus-sionorinconsultationwithathirdauthor(D.D.M.).
Assessment of Methodologic Quality 
We assessed the methodologic quality of included studies based on theNewcastle-Ottawa Scale (NOS) for quality of case-control studies in meta-analyses.
34
AstarsystemoftheNOS(range,0to9stars)hasbeendevelopedfortheassessment.Inthecurrentstudy,weconsideredastudyawarded7ormorestars as a high-quality study because standard criteria have not been estab-lished.Themeanvalueforthe23studiesassessedwas6.3stars.
Main and Subgroup Analyses 
Weinvestigatedtheassociationbetweentheuseofmobilephones(use
v 
never or rarely use, if possible) and the overall risk of all tumors by usingadjusted 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 crudedata), methodologic quality (high or low quality), type of tumor, malignancy of tumor (malignant or benign), type of mobile phone (analog or digital),lateralityoftumor(ipsilateralorcontralateral),andtypeofcase-controlstudy (hospital based or population based). Furthermore, we investigated the asso-ciation between long-term mobile phone use (
10 years) and the risk of tumors,includingsubgroupanalysesbythefactorslistedearlier.
Statistical Analyses 
Tocomputeapooledoddsratiowith95%CI,weusedtheadjustedoddsratio and 95% CIs reported in each article whenever possible. We examinedheterogeneity in results across studies using Higgins I
2
, which measures thepercentage of total variation across studies.
35
We considered an I
2
value of greaterthan50%asindicativeofsubstantialheterogeneity.When substantial heterogeneity was not observed, the pooled estimatecalculated based on the fixed-effects model was reported using the Woolf’s(inversevariance)method.Whensubstantialheterogeneitywasobserved,thepooled estimate calculated based on the random-effects model was reportedusingtheDerSimonianandLairdmethod.
36
Weevaluatedpublicationbiasofthestudiesincludedinthefinalanalysisusing Begg’s funnel plot and Egger’s test. If publication bias exists, Begg’sfunnelplotisasymmetricorthe
P 
valueislessthan.05byEgger’stest.Also,ameta-regression analysis was performed to assess the effect of subgroups andstudy characteristics, such as research group, year of publication, type of tumor, and study design, on the study results. Blinding and methodologicquality were excluded because of multicollinearity with research group. Weused Stata SE version 10.0 software package (StataCorp, College Station, TX)forstatisticalanalysis.
RESULTS
Identification of Relevant Studies 
Figure 1 shows a flow diagram of how we identified relevantstudies.Atotalof465articleswereidentifiedbysearchingthreedata-bases and hand-searching relevant bibliographies. We excluded 135duplicatearticlesandanadditional287articlesthatdidnotsatisfytheselection criteria. After reviewing the full texts of the remaining 43articles, 21 articles
37-57
were excluded because of several reasons, asshown in Figure 1. The remaining 23 case-control studies from 22articles
7-28
wereincludedinthefinalanalysis(thestudybyAuvinenetal
11
wasconsideredastwoindividualcase-controlstudies).
Characteristics of Studies Included in the Final Analysis 
In the 23 case-control studies, we identified a total of 37,916participants (12,344 patient cases and 25,572 controls). For studiesreporting age and sex, the mean age was 52.6 years (range, 18 to 90 years),and51%oftheparticipantswerewomen.Appendix Table A1 (online only) shows the general characteris-tics of the 23 case-control studies (22 articles) included in the finalanalysis. The percentage of study participants who reported havingused a mobile phone was 43.5% among the patient cases and 45.2%amongthecontrols(datanotshowninAppendixTableA1).
Identified studies from the databases using keywords and bibliographies ofrelevant articles (N = 465):PubMed (n = 255), EMBASE (n = 183), Cochrane Library (n = 25),and bibliographies (n = 2)Articles remaining after excluding duplicates (n = 330)Remaining articles (n = 43), full text reviewExclude duplicate articles (n = 135)Exclude according to selection criteria (n = 287)23 case-control studies among 22 articles* included in the final analysisExcluded articles (n = 21):Shared an identical population (n = 8)Included totally or partly in another article (n = 10)Letter, comments, or correspondence (n = 3)
Fig 1.
Flow diagram for identification of relevant case-control studies. (*) Onearticle (Auvinen et al
11
) was divided into two studies because it involved twodifferent types of tumors.
Myung et al
2
© 2009 by American Society of Clinical Oncology
J
OURNAL OF
C
LINICAL
O
NCOLOGY
Copyright © 2009 by the American Society of Clinical Oncology. All rights reserved.Information downloaded from jco.ascopubs.org and provided by National Cancer Center on October 13, 2009 from .
 
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 tumorsinarandom-effectsmodelmeta-analysisofall23case-controlstudies (odds ratio
0.98; 95% CI, 0.89 to 1.07). However, a signifi-cant positive association (ie, harmful effect) was observed in eightstudies
7,12,14-16,18,23
andonestudybyanothergroup
10
)usingblinding(oddsratio
1.17;95%CI,1.02to1.36),whereasasignificantnega-tiveassociation(ie,protectiveeffect)wasobservedin15studies(nineINTERPHONE-related studies
17,20-22,24-28
and six studies by othergroups
8,9,11,13,19
)notusingblinding(oddsratio
0.85;95%CI,0.80to 0.91). No publication bias was observed in the selected studies(Begg’sfunnelplotwassymmetric;Egger’stest,
P 
forbias
.21;Fig3).Table1showsthemethodologicqualityofstudiesincludedinthefinalanalysis.Therangeofqualityscoreswas5to8;theaveragescorewas 6.3. The high-quality studies (score of 
7) included all seven of thestudiesbyHardelletal,oneINTERPHONE-relatedstudy,andtwostudies by other groups. The low-quality studies (score of 
7) in-cluded eight INTERPHONE-related studies and six studies by othergroups.Asubgroupmeta-analysisbyresearchgroupshowedasignificantpositiveassociationforthesevenstudiesreportedbyHardelletalbuta significant negative association for nine INTERPHONE-relatedstudies(Table2).Whenusingcrudedata,asignificantassociationwasnot found in any of the 23 studies or in subgroup analyses by re-searchgroup.Subgroup meta-analyses by methodologic quality of study re-vealed a significant positive association in the high-quality studies(oddsratio
1.09;95%CI,1.01to1.18),whereasanegativeassocia-tion was observed in the low-quality studies. In subgroup meta-analyses by malignancy of tumor, no significant association wasobservedformalignanttumors.However,asignificantnegativeasso-ciation was observed for benign tumors. Neither the use of analogphones 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 theriskoftumorsinthe12studiesreportingtumorlaterality.
Mobile Phone Use of 10 Years or Longer and Risk of Tumors 
Among the 23 studies, there was a significant positive associ-ation between mobile phone use of 10 years or longer and the riskof tumors in a fixed-effects meta-analysis of 13 studies reportingthis 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
Overall (I
2
= 59.7%)
Hours
et al (
2007)
Hardell et al (2005, I)Hardell et al (2005, N)
Studies using blinding (n = 8)
Schoemaker et al (2005)Hardell et al (2007
)
Takebayashi et al (
2006)Schuz
et al (
2006)
Warren et al (2003)
Linet
et al (
2006)
Auvinen et al (2002
,
B)Hardell et al (2006
)
Hardell et al (2004
)
Takebayashi et al (2008
)
Sadetzki et al (2008
)
Muscat et al (2000
)
Hardell et al (2002
)
Subtotal (I
2
= 54.7%)
Lahkola et al (2007
)Stang
et al (
2001)
Hardell et al (1999)Lahkola et al (2008
)
Subtotal (I
2
= 0.0%)
Lonn
et al (
2006)
Auvinen et al (2002, A
)
Study
Inskip
et al (
2001)
0.98 (0.89 to 1.07)
0.93 (0.69 to 1.27)1.06 (0.87 to 1.31)1.40 (1.03 to 1.90)
OR (95% CI)
0.90 (0.70 to 1.10)1.00 (0.80 to 1.20)0.73 (0.43 to 1.23)0.91 (0.75 to 1.11)0.60 (0.20 to 1.90)1.00 (0.70 to 1.30)1.30 (0.40 to 4.70)1.90 (1.30 to 2.70)1.02 (0.75 to 1.38)0.87 (0.63 to 1.22)0.87 (0.68 to 1.13)0.85 (0.60 to 1.20)1.15 (0.99 to 1.33)0.78 (0.68 to 0.91)2.80 (1.00 to 7.90)0.98 (0.69 to 1.41)0.76 (0.65 to 0.89)
0.85 (0.80 to 0.91)
0.80 (0.54 to 1.20)1.30 (0.90 to 1.80)0.90 (0.70 to 1.10)
100.00
4.426.034.40
Weight (%)
5.666.07
1.17 (1.02 to 1.36)36.08
2.266.180.624.360.523.654.424.075.193.877.047.070.723.746.88
63.92
3.283.875.661.2.525
Studies not using blinding (n = 15)Heterogeneity between groups:
P 
< .001
Fig 2.
Overall use of mobile phones andthe risk of tumors in a random-effectsmodel meta-analysis of case-controlstudies
7-28
by the use of blinding at aninterview for exposure measurements(n
23). OR, odds ratio; Hardell et al(2005, I) indicates reference 15; Hardell etal (2005, N) indicates reference 16.
    l   o   g    O    R
Standard error of log OR
0.2.4.6-2-101
Egger’s test:
P 
for bias = .21
Fig 3.
Begg’s funnel plots and Egger’s test for identifying publication bias(
P 
.21) in a meta-analysis of case-control studies
7-28
(n
23). OR, odds ratio.
Meta-Analysis of Mobile Phone Use and Risk of Tumor
www.jco.org 
© 2009 by American Society of Clinical Oncology
3
Copyright © 2009 by the American Society of Clinical Oncology. All rights reserved.Information downloaded from jco.ascopubs.org and provided by National Cancer Center on October 13, 2009 from .
of 00

Leave a Comment

You must be to leave a comment.
Submit
Characters: ...
You must be to leave a comment.
Submit
Characters: ...