Brain Tumour Risk in Relation to Mobile Telephone Use: Results of the INTERPHONE International Case-control Study

The INTERPHONE Study Group

Disclosures

Int J Epidemiol. 2010;39(3):675-694. 

In This Article

Results

During the study period, 3115 meningioma and 4301 glioma cases, and 14 354 potential controls were identified. Interviews were completed with 2425 meningioma cases (78%; range 56–92%), 2765 glioma cases (64% participation; range by centre 36–92%) and 7658 controls (53%; range 42–74%; Appendix 1, Table 1, Supplementary data are available at IJE online). The most common reasons for non-participation were subject refusal (11% of meningiomas, 11% of glioma cases and 30% of controls); illness, death or physician refusal (4% of meningiomas, 20% of gliomas and 1% of controls); and inability to contact the subject (7% of meningiomas, 5% of gliomas and 15% of controls).

The main analyses, based on matched sets only, included 2409 meningioma cases with 2662 matched controls and 2708 glioma cases with 2972 matched controls. Among meningioma cases, 24% were men and 76% women; among glioma cases, 60% were men and 40% women (Table 1). Although the median age of meningioma cases was only slightly older than that of glioma cases (51 and 49 years, respectively), 23% of glioma cases were diagnosed before the age of 40, compared with 13% of meningioma cases.

The proportion of proxy interviews was higher in glioma cases (13%) than in controls (1%) or meningioma cases (2%). Whereas 17% of glioma cases who were regular users had imputations because of missing information in at least one of their mobile phone-related variables, the corresponding fractions were 9% among regular user meningioma cases and 8% among regular user controls. The proportion of subjects who answered questions about mobile phone use by giving a range of values rather than a particular amount of use (for any of the use dimensions) was very similar (~42%) for meningioma cases, glioma cases and controls.

The prevalence of regular mobile phone use 1 year before the reference date was 52% for meningioma cases (ranging from 34 to 73% across study centres) and 56% in matched controls (35–78%). It was higher for glioma cases (62% overall, range: 42–80%) and controls (64% overall, range: 45–84%), reflecting the different sex distributions of these tumours.

The majority of subjects in the study were not heavy mobile phone users; the median lifetime cumulative call time among meningioma controls using mobile phones was ~75 h, with a median call time of ~2 h/month and a median lifetime number of calls about 1500. Corresponding values for glioma controls were ~100 h lifetime, 2.5 h/month and about 2000 calls. The distributions of time since start of mobile phone use and cumulative call time were highly skewed, with few long-term and heavy users, and varied across study centres and by age and sex (not shown).

Relation between Mobile Phone Use and Risk of Brain Tumours

Meningioma A reduced OR of meningioma was found for regular mobile phone use in the past ≥1 year, OR 0.79 [95% confidence interval (CI) 0.68–0.91; Table 2]. There was some suggestion of heterogeneity of risk across centres (P = 0.08) with ORs <1.0 except in Canada, Denmark, Germany and Italy (data not shown). ORs were <1.0 for regular users in all categories of time since start of use and cumulative number of calls. Analyses by cumulative call time showed ORs <1.0 in the first nine deciles and an OR of 1.15 (95% CI 0.81–1.62) in the highest decile. Analyses of cumulative call time among recent-, medium- and long-term users (Table 3) showed no indication of excess risk except in the highest call time category in those who started phone use 1–4 years before the reference date: OR 4.80 (95% CI 1.49–15.4).

There was no appreciable effect modification by age or sex on any of these results (data not shown).

In analyses by anatomical location of the meningioma, the OR for temporal lobe tumours with regular use was 0.55 (95% CI 0.36–0.82) and the ORs were <1.0 in all categories of time since start of use, cumulative call time and cumulative number of calls. ORs for other lobes were also mostly <1.0 (Table 4).

The OR for mainly ipsilateral use among regular users was 0.86 (95% CI 0.69–1.08), and that for contralateral use was 0.59 (95% CI 0.46–0.76; Table 5). The ORs by time since start of use were <1.0 in all categories of ipsilateral and contralateral use. When analysing by any of the exposure metrics in Table 5, the ratios of the ORs for ipsilateral use to contralateral use were always one or above one regardless of level of exposure and they were highest (~2 or 3) for the two highest categories of cumulative call time and the second highest category of cumulative number of calls. A case–case analysis, based on Inskip's method, showed an OR of 1.07 (95% CI 1.00–1.16; Appendix 1, Table 2, Supplementary data are available at IJE online) for ipsilateral use.

The OR for those who reported regular use of only an analogue phone was 0.81 (95% CI 0.65–1.03) and for only a digital phone it was 0.79 (95% CI 0.68–0.92). Focussing on the highest decile of cumulative call time, the OR among those who used only an analogue phone was 0.50 (95% CI 0.25–0.99); among those who used only a digital phone it was 1.84 (95% CI 1.17–2.88); and among those using both 4.43 (95% CI 1.42–13.9; Appendix 1, Table 3, Supplementary data are available at IJE online).

Glioma A reduced risk of glioma was seen for regular mobile phone use in the past ≥1 year (OR 0.81, 95% CI 0.70–0.94; Table 2) relative to never regular users. There was little evidence of heterogeneity in results across centres (P = 0.68). ORs were <1.0 in all study centres except Australia, France and New Zealand.

Analyses by time since start of use showed a reduced OR in all categories of use; the OR for ≥10 years since start of use was 0.98 (95% CI 0.76–1.26; Table 2). The pattern of results by duration of mobile phone use was similar (data not shown).

Analyses by categories of cumulative call time showed decreased ORs in eight of the first nine deciles (five of which had upper confidence bounds <1.0) and an increased OR of 1.40 (95% CI 1.03–1.89) in the highest exposure category, ≥1640 h. Analyses by cumulative number of calls showed ORs <1.0 in all categories, with the OR in the highest decile approaching unity.

Analyses of cumulative call time stratified by short-, medium- and long-term use (Table 3) showed reduced risks in the lower call time categories in all strata of time since start of use and ORs >1.0 in the highest category (≥1640 h cumulative call time) in each of the three strata. The highest OR was in the short-term users but its CI was very wide.

The lobe of the brain in which the tumour was located was known for 96% of cases. The OR for temporal lobe tumours with regular use was 0.86 (95% CI 0.66–1.13; Table 4). The point estimates for the highest categories of cumulative call time, cumulative number of calls and time since start of use were higher for tumours in the temporal lobe than in other locations, but their 95% CIs were wide. Only for the highest decile of cumulative call time was the OR for temporal lobe tumours appreciably elevated (1.87, 95% CI 1.09–3.22).

For regular use in the past ≥1 year, the OR for ipsilateral mobile phone use was 0.84 (95% CI 0.69–1.04) and that for contralateral use was 0.67 (95% CI 0.52–0.87; Table 5). The ORs by time since start of use were <1.0 in all categories, except for ipsilateral use beginning ≥10 in the past (OR 1.21, 95% CI 0.82–1.80). The ORs by cumulative number of calls were <1.0 irrespective of laterality and exposure level, except for ipsilateral use in the two highest categories. The results by cumulative call time showed a similar pattern, but the OR for ipsilateral use in the highest category was appreciably elevated (OR 1.96, 95% CI 1.22–3.16) and that for contralateral use was slightly elevated (OR 1.25, 95% CI 0.64–2.42). The ratios of the ipsilateral ORs to the contralateral ORs were all above one with one exception (0.99 for 2–4 years since start of use) and the highest (~2) were in 1–1.9 and ≥10 years since start of use, the lowest category of cumulative call time, and the highest category of cumulative number of calls. For cumulative number of calls, there was a consistent trend towards increasing ratios with increasing exposure.

Case–case analyses of the concordance between tumour side and preferred side of phone use using the Inskip method showed an elevated risk for ipsilateral use among regular users (OR 1.27, 95% CI 1.19–1.37) and among those in the highest decile of cumulative call time (OR 1.55, 95% CI 1.24–1.99; Appendix 1, Table 2, Supplementary data are available at IJE online). When stratified on time since first use, the point estimate of the OR using Inskip's method in the highest decile was higher among short-term heavy users (OR 2.37, 95% CI 0.93–8.59) than among medium (OR 1.40, 95% CI 1.04–2.01) and long-term (OR 1.57, 95% CI 1.13–2.30) heavy users, resembling an analogous pattern in Table 3.

The OR for ever use of an analogue phone was 1.00 (95% CI 0.83–1.21) and for ever use of a digital phone 0.76 (95% CI 0.66–0.88). Increased ORs were seen in the highest decile of cumulative call time with analogue phones (OR 1.95, 95% CI 1.08–3.54) and with digital phones (OR 1.46, 95% CI 0.98–2.17; Appendix 1, Table 3, Supplementary data are available at IJE online).

There was no evidence of heterogeneity of effects across centres for cumulative call time, cumulative number of calls, time since start of use or ipsilateral or contralateral use. Nor was there any appreciable effect modification by age or sex in any of the results mentioned above (data not shown).

Sensitivity Analyses

Selected findings of sensitivity analyses are shown in Table 6 and Appendix 1, Table 4 (Supplementary data are available at IJE online). Because of a hint of a possible excess risk in subjects in the highest decile of mobile phone cumulative call time, for glioma (OR 1.40) and to a lesser extent for meningioma (OR 1.15), we focus presentation of sensitivity analyses on the findings in this highest decile, corresponding to 1640 or more cumulative hours of use.

For meningioma, some point estimates differed from the OR of 1.15 from the main analysis, but the estimates were imprecise and, with one exception based on nine cases and four controls, fell well within the CI of this 'benchmark' value.

For glioma, results from the various sensitivity analyses were generally similar to those from the primary analysis. All the OR estimates, except one based on nine cases and three controls, are well within the 95% CI of the OR from the main analysis. When subjects with high reported use were included, but with use truncated at 5 h/day, the OR was hardly affected. When subjects who reported >5 h call time/day (38 cases and 22 controls) were excluded altogether, on the premise that such responses were unreliable, the OR decreased to 1.27 (95% CI 0.92–1.75).

Results of sensitivity analyses focusing on the OR for regular use in the past ≥1 year are shown in Appendix 1, Table 5 (Supplementary data are available at IJE online). All the OR estimates, except two ORs for meningioma relating to the presentation of the study, are well within the 95% CI of the OR from the main analysis.

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