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.

We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in August 2008. Two evaluators independently reviewed and selected articles based on predetermined selection criteria.

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 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 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.

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.

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 high-frequency EMFs on cell proliferation and activation of oncogene transcription,46 those biologic effects and mechanisms in developing neoplasm remain unclear. Over the past decade, epidemiologic 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-Hodgkin's lymphoma, and testicular cancer.728

Some case-control studies have suggested a positive (ie, harmful) association between the use of mobile phones and the risk of tumors,7,1012,1518,23,25,27 whereas other case-control studies have reported no significant association.8,9,11,13,14,1922,24,26,28 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.3133 However, these meta-analyses 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.

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 meta-analyses.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 Woolf's (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 Begg's funnel plot and Egger's test. If publication bias exists, Begg's funnel plot is asymmetric or the P value is less than .05 by Egger's 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 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.

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 articles3757 were excluded because of several reasons, as shown in Figure 1. The remaining 23 case-control studies from 22 articles728 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).

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 studies7,12,1416,18,23 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 studies17,2022,2428 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 (Begg's funnel plot was symmetric; Egger's test, P for bias = .21; Fig 3).

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.

Table

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

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 Selection (score)
Comparability (score)
Exposure (score)
Total Score
Adequate Definition of Patient Cases Representativeness of Patient Cases Selection of Controls Definition of Controls Control for Important Factor or Additional Factor Ascertainment of Exposure (blinding) Same Method of Ascertainment for Participants Nonresponse Rate*
Hardell et al7 1 1 1 0 1 1 1 1 7
Muscat et al8 1 0 0 1 2 0 1 0 5
Inskip et al9 1 0 0 1 2 0 1 0 5
Stang et al10 (hospital based) 1 1 0 0 2 1 1 0 6
Stang et al10 (population based) 1 1 1 0 2 1 1 0 7
Auvinen et al11 1 1 1 1 1 1 0 1 0 6
Auvinen et al11 2 1 1 1 1 1 0 1 0 6
Hardell et al12 1 1 1 0 2 1 1 0 7
Warren et al13 1 1 0 1 1 0 1 0 5
Hardell et al14 1 1 1 0 1 1 1 1 7
Hardell et al15 1 1 1 0 2 1 1 1 8
Hardell et al16 1 1 1 0 2 1 1 0 7
Schoemaker et al17 1 1 1 1 2 0 1 0 7
Hardell et al18 1 1 1 0 2 1 1 1 8
Linet et al19 1 1 1 1 2 0 1 0 7
Lönn et al20 1 1 1 0 2 0 1 0 6
Schüz et al21 1 1 1 0 2 0 1 0 6
Takebayashi et al22 1 1 1 0 2 0 1 0 6
Hardell et al23 1 1 1 0 2 1 1 1 8
Hours et al24 1 1 1 0 2 0 1 0 6
Lahkola et al25 1 1 1 0 2 0 1 0 6
Lahkola et al26 1 1 1 0 1 0 1 0 5
Sadetzki et al27 1 1 1 0 1 0 1 0 5
Takebayashi et al28 1 1 1 0 2 0 1 0 6

*When there was no significant difference in the response rate between both groups by using a χ2 test (P > .05), one point was awarded.

†Total score could range from 0 to 9 points.

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.

Table

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

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 23 0.98 0.89 to 1.07 59.7 Random effects
Research group
    Hardell et al* 7 1.15 1.01 to 1.32 52.1 Random effects
    INTERPHONE 9 0.83 0.77 to 0.89 0 Fixed effects
    Other groups 7 0.99 0.86 to 1.14 30.6 Fixed effects
Research group (crude data) 23 0.97 0.87 to 1.08 73.6 Random effects
    Hardell et al 7 1.14 0.96 to 1.35 71.0 Random effects
    INTERPHONE 9 0.88 0.75 to 1.03 79.8 Random effects
    Other groups 7 0.90 0.79 to 1.03 22.6 Fixed effects
Methodologic quality
    High (low bias: ≥ 7 points)* 10 1.09 1.01 to 1.18 46.3 Fixed effects
        Hardell et al* 7 1.15 1.00 to 1.32 52.1 Random effects
        INTERPHONE 1 0.90 0.70 to 1.10 NA NA
        Other group 2 1.02 0.75 to 1.38 0 Fixed effects
    Low (high bias: < 7 points) 14 0.85 0.79 to 0.91 5.7 Fixed effects
        INTERPHONE 8 0.82 0.76 to 0.88 0 Fixed effects
        Other groups 6 0.97 0.83 to 1.14 24.2 Fixed effects
Malignancy of tumor
    Malignant 15 1.00 0.89 to 1.13 52.0 Random effects
        Hardell et al 6 1.11 0.96 to 1.29 50.5 Random effects
        INTERPHONE 4 0.78 0.67 to 0.91 0 Fixed effects
        Other groups 5 0.97 0.80 to 1.18 19.6 Fixed effects
    Benign 15 0.87 0.80 to 0.95 20.7 Fixed effects
        Hardell et al 4 1.17 0.97 to 1.42 3.8 Fixed effects
        INTERPHONE 8 0.81 0.73 to 0.90 0 Fixed effects
        Other groups 3 0.82 0.61 to 1.11 0 Fixed effects
Type of mobile phone
    Analog 12 0.96 0.87 to 1.07 49.9 Fixed effects
        Hardell et al 7 1.04 0.89 to 1.22 34.5 Fixed effects
        INTERPHONE 3 0.84 0.72 to 0.96 0 Fixed effects
        Other groups* 2 1.55 1.08 to 2.2 0 Fixed effects
    Digital 14 0.95 0.84 to 1.08 55.8 Random effects
        Hardell et al 7 1.10 0.97 to 1.24 12.7 Fixed effects
        INTERPHONE 5 0.78 0.71 to 0.85 0 Fixed effects
        Other groups 2 0.93 0.55 to 1.59 0 Fixed effects
Laterality of tumor
    Ipsilateral 12 1.22 0.99 to 1.51 85.9 Random effects
        Hardell et al* 4 1.80 1.24 to 2.62 84.9 Random effects
        INTERPHONE 8 1.00 0.91 to 1.10 37.0 Fixed effects
    Contralateral 11 0.94 0.77 to 1.15 82.3 Random effects
        Hardell et al 3 1.31 0.74 to 2.31 93.0 Random effects
        INTERPHONE 8 0.81 0.74 to 0.89 48.2 Fixed effects
Type of case-control study
    Hospital based (all other groups) 4 0.89 0.74 to 1.07 0.0 Fixed effects
    Population based 20 0.99 0.89 to 1.09 61.8 Random effects
        Hardell et al* 7 1.15 1.01 to 1.32 52.1 Random effects
        INTERPHONE 9 0.83 0.77 to 0.89 0 Fixed effects
        Other groups 4 1.14 0.91 to 1.43 0 Fixed effects

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

*Statistically significant positive association.

†Statistically significant negative association.

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 meta-analyses 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 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.7,12,1416,18,23 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.

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.

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. 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.

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 INTERPHONE-related studies.

Besides blinding and methodologic quality of studies, we should consider two potential biases regarding the differences we found by research groups—recall bias and selection bias, both of which have been described in detail elsewhere.57 In a validation study of short-term 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, reported 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-analyses3133 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 al7,12,1416,18,23 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 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,6,6163 the effect of high-frequency EMF exposure on health is still controversial.6470

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 al7,12,1416,18,23 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, especially among users of 10 or more years. Furthermore, we found a large discrepancy in the association between mobile phone use and tumor risk by research group, which is confounded with the methodologic quality of the research. Our findings should be confirmed in prospective cohort studies to provide a higher level of evidence.

© 2009 by American Society of Clinical Oncology

Written on behalf of the Korean Meta-Analysis (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.

The author(s) indicated no potential conflicts of interest.

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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Table

Table A1. Characteristics of Studies Included in the Final Meta-Analysis of Mobile Phone Use and Risk of Tumors

Table A1. Characteristics of Studies Included in the Final Meta-Analysis of Mobile Phone Use and Risk of Tumors

Study Year of Publication Country and Study Name Study Design Study Period Study Length (years) Type of Tumor Type of Mobile Phone and Exposure Study OR 95% CI Adjustment Exposed
Unexposed
No. of Patient Cases No. of Controls No. of Patient Cases No. of Controls
Hardell et al7 1999 Sweden PCC 1994-1996 2 Malignant and benign brain tumors (gliomas, meningiomas, and acoustic neuromas) Cellular phone (analog and digital); latency period > 1 year v within 1 year Hardell et al7 0.98 0.69 to 1.41 Age, sex, and study region (matched) 78 161 131 264
Muscat et al8 2000 United States HCC 1994-1998 4 Primary brain cancers (gliomas and other malignant brain tumors) Handheld cellular phone; regular past or current use v never use Muscat et al8 0.85* 0.6 to 1.2 Age, years of education, sex, race, study center, proxy subject, and month and year of interview 66 76 403 346
Inskip et al9 2001 United States HCC 1994-1998 4 Malignant and benign brain tumors (gliomas, meningiomas, and acoustic neuromas) Handheld cellular phone; cumulative use of > 100 hours v never or rarely use Inskip et al9 0.9* 0.7 to 1.1 Date of interview, type of respondent, educational level, annual household income, type of health coverage, marital status, religion, history of radiotherapy to the head or neck, and handedness 52 54 637 625
Stang et al10 2001 Germany HCC and PCC 1995-1998 3 Uveal melanomas Mobile phone; possible/probable/certain ever exposure v never exposure Stang et al10 2.8 1.0 to 7.9 Social class with 9 years at school or less 7 25 111 450
Auvinen et al11 2002 Finland PCC 1996 Malignant and benign brain tumors (gliomas and meningiomas) and salivary gland cancers Cellular phone (analog and digital); ever use v never use Auvinen et al11 Brain tumors: 1.3; salivary gland cancers: 1.3 Brain tumors: 0.9 to 1.8; salivary gland cancers: 0.4 to 4.7 Place of residence, occupation, and socioeconomic status Brain tumors: 56; salivary gland cancers: 4 Brain tumors: 223; salivary gland cancers: 18 Brain tumors: 342; salivary gland cancers: 30 Brain tumors: 1,763; salivary gland cancers: 152
Hardell et al12 2002 Sweden PCC 1997-2000 3 Malignant and benign brain tumors (gliomas, meningiomas, pituitary tumors, and acoustic neuromas) Cellular or cordless phone (analog and digital); use v no use Hardell et al12 Analog cellular phone: 1.3*; digital cellular phone: 1.0*; cordless phone: 1.0*; combined OR: 1.15 Analog cellular phone: 1.04 to 1.6; digital cellular phone: 0.8 to 1.2; cordless phone: 0.8 to 1.2; combined OR: 0.99 to 1.33 Use of different types of phones 650 618 779 852
Warren et al13 2003 United States HCC 1995-2000 5 Intratemporal facial nerve tumors Handheld cellular phone; use v no use Warren et al13 0.6 0.2 to 1.9 Age, sex, and race (matched) 5 53 13 88
Hardell et al14 2004 Sweden PCC 1994-2000 6 Malignant and benign salivary gland tumors Cellular or cordless phone; use v no use Hardell et al14 1.02* 0.75 to 1.38 Age and sex 91 352 176 701
Hardell et al15 2005 Sweden PCC 1999-2002 3 Non-Hodgkin's lymphomas Cellular or cordless phone (analog and digital); use v no use Hardell et al15 1.06* 0.87 to 1.31 Age, sex, and year of diagnosis (patient cases) or enrollment (controls) 607 695 303 321
Hardell et al16 2005 Sweden PCC 2000-2003 3 Benign brain tumors (meningiomas, acoustic neuromas, and other benign brain tumors) Cellular or cordless telephone (analog and digital); use v no use Hardell et al16 1.4* 1.03 to 1.9 Age, sex, socioeconomic index, and year of diagnosis 290 459 123 233
Schoemaker et al17 2005 Five North European countries: Denmark, Finland, Norway, Stockholm, and United Kingdom; followed a protocol of the INTERPHONE Study PCC 1999-2004 5 Benign brain tumors (acoustic neuromas) Mobile phone (analog and digital); regular use v never or nonregular use Schoemaker et al17 0.9* 0.7 to 1.1 Highest educational level and combination of interview year and interview lag time 360 1,934 316 1,612
Hardell et al18 2006 Sweden PCC 2000-2003 3 Malignant brain tumors (gliomas and other malignant tumors) Cellular or cordless phone (analog and digital; use v no use Hardell et al18 1.9* 1.3 to 2.7 Age, sex, socioeconomic index, and the year of diagnosis 254 459 63 233
Linet et al19 2006 United States PCC 1998-2000 2 Non-Hodgkin's lymphomas Cellular phone; lifetime ever use v never use Linet et al19 1.0* 0.7 to 1.3 Age, race, education, and geographic site 317 247 234 215
Lönn et al20 2006 Denmark and Sweden; part of the INTERPHONE Study PCC 2000-2002 2 Malignant and benign parotid gland tumors Mobile phone; regular use v never or rarely use Lönn et al20 0.80* (combined ORs of malignant parotid gland and benign pleomorphic adenoid) 0.54 to 1.20 Age, sex, geographic region, and education 102 603 70 399
Schüz et al21 2006 Germany; part of the INTERPHONE Study PCC 2000-2003 3 Malignant and benign brain tumors (glioma and meningioma) Cellular phone; ever regular use v never use Schüz et al21 0.91* (combined ORs of glioma and meningioma) 0.75 to 1.1 Age, socioeconomic status, and living in a city 242 517 505 977
Takebayashi et al22 2006 Japan; followed a protocol of the INTERPHONE Study PCC 2000-2004 4 Benign brain tumors (acoustic neuromas) Mobile phone (analog and digital); regular use v no use Takebayashi et al22 0.73* 0.43 to 1.23 Education and marital status 51 192 46 138
Hardell et al23 2007 Sweden PCC 1993-1997 4 Testicular cancers (seminomas and nonseminomas) Cellular or cordless phone; use v not use Hardell et al23 1.0* 0.8 to 1.2 Age, year of diagnosis, and cryptorchidism 372 358 516 512
Hours et al24 2007 France; part of the INTERPHONE Study PCC 2001-2003 2 Malignant and benign brain tumors (gliomas, meningiomas, and acoustic neuromas) Mobile phone; regular use v no or nonregular use Hours et al24 0.93* 0.69 to 1.27 Socioeconomic status, smoking status, and marital status 188 257 162 198
Lahkola et al25 2007 5 North European countries: Denmark, Finland, Norway, Sweden, and United Kingdom; followed a protocol of the INTERPHONE Study PCC 2000-2004 4 Malignant brain tumors (gliomas) Mobile phone (analog and digital); regular use v never or nonregular use Lahkola et al25 0.78* 0.68 to 0.91 Education and family history of glioma 867 1,853 629 1,281
Lahkola et al26 2008 5 North European countries: Denmark, Finland, Norway, Sweden, and United Kingdom; followed a protocol of the INTERPHONE Study PCC 2000-2004 4 Benign brain tumors (meningiomas) Mobile phone (analog and digital); regular use v never or nonregular use Lahkola et al26 0.76 0.65 to 0.89 Sex, 5-year age group, region, and county (matched) 573 1,696 631 1,249
Sadetzki et al27 2008 Israel; followed a protocol of the INTERPHONE Study PCC 2001-2003 2 Malignant and benign parotid gland tumors Cellular phone; regular use v nonregular use (< 1 year) Sadetzki et al27 0.87* 0.68 to 1.13 Cigarette smoking 285 691 175 575
Takebayashi et al28 2008 Japan; followed a protocol of the INTERPHONE Study PCC 2000-2004 4 Malignant and benign brain tumors Mobile phone (analog and digital; regular use v no use Takebayashi et al28 0.87* (combined ORs of glioma, meningioma, and pituitary) 0.63 to 1.22 Education and marital status 173 329 139 224

Abbreviations: OR, odds ratio; PCC, population-based case-control study; HCC, hospital-based case-control study.

*Adjusted OR.

Table

Table A2. Mobile Phone Use of 10 Years or Longer (v never or rarely use) and the Risk of Tumors in Subgroup Meta-Analyses

Table A2. Mobile Phone Use of 10 Years or Longer (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* 13 1.18 1.04 to 1.34 33.1 Fixed effects
Research group
    Hardell et al* 7 1.35 1.14 to 1.59 35.1 Fixed effects
    INTERPHONE 6 0.99 0.82 to 1.21 0 Fixed effects
Methodologic quality
    High (low bias: ≥ 7 points)* 8 1.32 1.12 to 1.54 29.1 Fixed effects
        Hardell et al* 7 1.35 1.14 to 1.59 35.1 Fixed effects
        INTERPHONE 1 1.10 0.70 to 1.80 NA NA
    Low (high bias: < 7 points, all INTERPHONE) 5 0.97 0.79 to 1.21 0 Fixed effects
Type of tumor
    Brain tumor* 8 1.24 1.00 to 1.55 50.8 Random effects
        Hardell et al* 4 1.54 1.26 to 1.89 0 Fixed effects
        INTERPHONE 4 1.00 0.81 to 1.22 10.9 Fixed effects
    Other tumors 5 1.00 0.76 to 1.30 0 Fixed effects
        Hardell et al 3 1.00 0.74 to 1.35 0 Fixed effects
        INTERPHONE 2 0.97 0.54 to 1.77 0 Fixed effects
Malignancy of tumor
    Malignant 7 1.15 0.78 to 1.71 58.8 Random effects
        Hardell et al 4 1.42 0.94 to 2.14 54.5 Random effects
        INTERPHONE 3 0.74 0.50 to 1.11 0 Fixed effects
    Benign* 8 1.33 1.11 to 1.58 39.3 Fixed effects
        Hardell et al* 3 1.66 1.32 to 2.09 1.9 Fixed effects
        INTERPHONE 5 0.98 0.75 to 1.28 0 Fixed effects
Type of mobile phone
    Analog* 10 1.34 1.07 to 1.66 29.8 Fixed effects
        Hardell et al* 7 1.52 1.19 to 1.95 0 Fixed effects
        INTERPHONE 3 0.82 0.51 to 1.32 0 Fixed effects
    Digital (all Hardell et al)* 3 1.68 1.01 to 2.81 0 Fixed effects
Laterality of tumor (all INTERPHONE)
    Ipsilateral* 5 1.32 1.02 to 1.70 0 Fixed effects
    Contralateral 4 0.89 0.68 to 1.15 0 Fixed effects

NOTE. All included studies were population-based case-control studies.

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

*Statistically significant positive association.

†Salivary gland tumor, non-Hodgkin's lymphoma, and testicular tumor.

Table

Table A3. Mobile Phone Use (versus never or rarely use) and the Risk of Brain Tumors in Subgroup Meta-Analyses

Table A3. Mobile Phone Use (versus never or rarely use) and the Risk of Brain Tumors in Subgroup Meta-Analyses

Factor No. of Studies Summary OR 95% CI of OR Heterogeneity, I2 (%) Model Used
All brain tumors 15 0.97 0.86 to 1.10 70.3 Random effects
Type of brain tumor
    Gliomas 10 1.09 0.89 to 1.34 67.9 Random effects
        Hardell et al 3 1.37 0.88 to 2.12 68.5 Random effects
        INTERPHONE* 4 0.84 0.75 to 0.96 33.9 Fixed effects
        Other groups 3 1.06 0.76 to 1.48 51.3 Random effects
    Meningiomas* 9 0.83 0.75 to 0.92 11.9 Fixed effects
        INTERPHONE* 4 0.77 0.68 to 0.88 0 Fixed effects
        Other groups 5 0.95 0.80 to 1.13 18.0 Fixed effects
    Acoustic neuromas 6 0.94 0.79 to 1.11 5.4 Fixed effects
        Hardell et al 2 1.38 0.92 to 2.08 0 Fixed effects
        INTERPHONE 3 0.88 0.72 to 1.07 0 Fixed Effecst
        Other groups 1 0.80 0.50 to 1.40 NA NA
Malignancy of brain tumor
    Malignant 7 0.99 0.79 to 1.23 74.1 Random effects
        Hardell et al 3 1.26 0.88 to 1.81 74.9 Random effects
        INTERPHONE* 2 0.77 0.65 to 0.91 0 Fixed effects
        Other groups 2 0.87 0.67 to 1.14 0 Fixed effects
    Benign* 12 0.87 0.80 to 0.95 31.0 Fixed effects
        Hardell et al 3 1.16 0.96 to 1.40 17.5 Fixed effects
        INTERPHONE* 6 0.80 0.72 to 0.89 0 Fixed effects
        Other groups 3 0.82 0.61 to 1.11 0 Fixed effects
Type of mobile phone
    Analog 8 1.02 0.83 to 1.24 62.2 Random effects
    Digital 10 0.92 0.79 to 1.07 62.5 Random effects
Laterality of brain tumor
    Ipsilateral 10 1.23 0.97 to 1.58 88.2 Random effects
    Contralateral 8 0.92 0.74 to 1.15 82.0 Random effects
Research group
    Hardell et al 4 1.29 1.02 to 1.64 64.6 Random effects
    INTERPHONE* 7 0.82 0.76 to 0.89 0 Fixed effects
    Other groups 4 0.96 0.81 to 1.13 31.7 Fixed effects
Methodologic quality
    High (low bias: ≥ 7 points) 5 1.19 0.96 to 1.49 71.7 Random effects
        Hardell et al 4 1.29 1.02 to 1.64 64.6 Random effects
        INTERPHONE 1 0.90 0.70 to 1.10 NA NA
    Low (high bias: < 7 points)* 10 0.84 0.78 to 0.91 16.2 Fixed effects
        INTERPHONE* 6 0.81 0.75 to 0.89 0 Fixed effects
        Other groups 4 0.96 0.81 to 1.13 31.7 Fixed effects
Interview blinded to patient case/control status
    Blinded (all Hardell et al) 4 1.29 1.02 to 1.64 64.6 Random effects
    Not blinded or no description* 11 0.85 0.79 to 0.91 9.5 Fixed effects
        INTERPHONE* 7 0.82 0.76 to 0.89 0 Fixed effects
        Other groups 4 0.96 0.81 to 1.13 31.7 Fixed effects

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

*Statistically significant negative association.

†Statistically significant positive association.

Table

Table A4. Mobile Phone Use (v never or rarely use) and the Risk of Tumors Other Than Brain Tumors in Subgroup Meta-Analyses

Table A4. Mobile Phone Use (v never or rarely use) and the Risk of Tumors Other Than Brain Tumors in Subgroup Meta-Analyses

Factor No. of Studies Summary OR 95% CI of OR Heterogeneity, I2 (%) Model Used
All 8 0.99 0.89 to 1.10 0 Fixed effects
Type of tumor
    Salivary gland tumor 4 0.91 0.76 to 1.08 0 Fixed effects
    Non-Hodgkin's lymphoma 2 1.04 0.88 to 1.24 0 Fixed effects
    Testicular cancer 1 1.00 0.80 to 1.20 NA NA
    Uveal melanoma* 1 2.80 1.00 to 7.90 NA NA
Malignancy of tumor
    Malignant 8 1.02 0.91 to 1.15 0 Fixed effects
        Hardell et al 3 1.03 0.90 to 1.17 0 Fixed effects
        INTERPHONE 2 0.84 0.54 to 1.31 0 Fixed effects
        Other groups 3 1.10 0.82 to 1.47 44.1 Fixed effects
    Benign 3 0.90 0.70 to 1.15 0 Fixed effects
        Hardell et al 1 2.03 0.55 to 7.50 NA NA
        INTERPHONE 2 0.87 0.68 to 1.12 0 Fixed effects
Type of mobile phone
    Analog 4 0.80 0.62 to 1.04 0 Fixed effects
        Hardell et al 3 0.80 0.61 to 1.03 0 Fixed effects
        Other group 1 1.00 0.30 to 4.00 NA NA
    Digital 4 1.10 0.89 to 1.31 0 Fixed effects
        Hardell et al 3 1.07 0.88 to 1.30 0 Fixed effects
        Other group 1 1.70 0.20 to 16.00 NA NA
Laterality of tumor (all INTERPHONE)
    Ipsilateral 2 1.12 0.89 to 1.42 24.7 Fixed effects
    Contralateral 2 0.78 0.60 to 1.01 20.6 Fixed effects
Research group
    Hardell et al 3 1.03 0.90 to 1.17 0 Fixed effects
    INTERPHONE 2 0.85 0.69 to 1.05 0 Fixed effects
    Other groups 3 1.10 0.82 to 1.47 44.1 Fixed effects
Methodologic quality
    High (low bias: ≥ 7 points) 3 1.02 0.90 to 1.17 0 Fixed effects
        Hardell et al 2 1.03 0.89 to 1.19 0 Fixed effects
        Other group 1 1.00 0.70 to 1.30 NA NA
    Low (high bias: < 7 points) 5 0.94 0.79 to 1.11 31.1 Fixed effects
        Hardell et al 1 1.02 0.75 to 1.38 NA NA
        INTERPHONE 2 0.85 0.69 to 1.05 0 Fixed effects
        Other groups 2 2.04 0.92 to 4.50 0 Fixed effects
Interview blinded to patient case/control status
    Blinded 4 1.04 0.92 to 1.19 19.3 Fixed effects
        Hardell et al 3 1.03 0.90 to 1.17 0 Fixed effects
        Other group* 1 2.80 1.00 to 7.90 NA NA
    Not blinded or no description 4 0.90 0.76 to 1.07 0 Fixed effects
        INTERPHONE 2 0.85 0.69 to 1.05 0 Fixed effects
        Other groups 2 1.02 0.75 to 1.37 0 Fixed effects

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

*Statistically significant positive association.

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ARTICLE CITATION

DOI: 10.1200/JCO.2008.21.6366 Journal of Clinical Oncology 27, no. 33 (November 20, 2009) 5565-5572.

Published online October 13, 2009.

PMID: 19826127

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