Scientific statement of the Federal Office for Radiation Protection concerning the results and conclusions of the INTERPHONE study

The rapid increase in mobile telephone use has led to general concerns about possible detrimental health risks that may be related to the high-frequency electromagnetic fields generated by this technology. The INTERPHOONE international case-control-study on the risk of brain tumours in relation to mobile telephone usage was initiated in 2000 by the International Agency for Research on Cancer (IARC). Since the absorption of the high-frequency electromagnetic fields during a mobile phone call occurs mostly in the head, the following tumours were considered: brain tumours (glioma and meningioma), tumours of the acoustic nerve (acoustic neuroma), and tumours of the parotid gland.

The INTERPHONE study

The INTERPHONE study involved extensive epidemiological data and detailed information on mobile phone usage from 13 countries (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden and the UK).

The aim of the INTERPHONE study was to assess possible risks for the development of following four types of primary brain tumours:

• glioma, which is the most common and most aggressive type of brain tumours and which arises from the glial cells
• meningioma, which is the second most common type of brain tumours and which arises from the meninges
• acoustic neuroma, which is a tumour of the acoustic nerve
• parotid gland tumours.

Patients diagnosed with such a tumour between 2000 and 2004 were included as cases. The study period ranged from two to four years in different countries. No analyses were performed with parotid gland tumours because the number of all cases of participating countries was too small.

The relevant findings of the INTERPHONE study were published in international scientific journals (INTERPHONE Study Group 2010, 2011; Swerdlow et al. 2011; Grell et al. 2016; Turner et al. 2016). They are presented and assessed in the following paragraphs.

Details of the German contribution to the INTERPHONE study, done within the framework of the German Mobile Telecommunication Research Programme (DMF), can be found on the webpages of the DMF.

Methods

The INTERPHONE study was a population based case-control study. 2,708 glioma patients, 2,409 meningioma patients, 1,105 acoustic neuroma patients, and matched controls were personally interviewed in a standardized way.

The study was conducted in 14 study centres in 13 countries: one study centre per country except in the UK where two study centres participated, one in north UK and one in south UK. The controls, matched by age, sex and region, were selected according to a locally adapted population-based sampling frame. One control per brain tumour case was selected from the corresponding population, except in Germany where two controls per case were drawn. Two controls were selected for acoustic neuroma cases in all countries.

The statistical analysis was performed with conditional logistic regression for matched sets with reference dates corresponding to case diagnoses. The odds ratio (OR) indicates how the detrimental health risk of an exposed person differs in relation to the risk of an unexposed person.

Exposure was assessed in various ways:

• ever having been a regular user (that is, having an average of at least one call per week for a period of at least 6 months)
• time in years since first regular use
• deciles of cumulative number of calls
• deciles of cumulative duration of calls

The reference category was defined as subjects who reported that they had never been regular mobile phone users.

Different types of analyses were conducted to account for the location of the gliomas and meningiomas in the brain lobes, and also with respect to preferred head-side for telephone usage (that is, whether the phone was used predominantly on the same side as the tumour or mainly on the side of the head opposite to the tumour).

Extensive supplementary analyses complemented the primary analysis to see if different study centre specific characteristics (for example study centre, method of calculating accumulated call time, use of matching and conditional analysis) may have introduced biases into the results.

Results

Main findings

A reduced OR related to ever having been a regular mobile phone user was seen for glioma [OR 0.81; [95 % confidence interval (95 % CI) 0.70-0.94]) and meningioma (OR 0.79; [ 95 % CI 0.68–0.91]). The analysis of acoustic neuromas was divided in two subgroups that showed the same tendency:

• regular users up to one year before diagnosis (OR 0.85; [95 % CI 0.69–1.04]) and
• regular users up to five years before diagnosis (OR 0.95; [95 % CI 0.77–1.17]).

The authors concluded that a protective effect of mobile phones on cancer was rather implausible and suggested that these results possibly reflected participation bias or other methodological limitations.

There was no association of time period since first regular mobile phone use with tumour risk. Even 10 years after first phone use there was no increase in risk for any of the considered brain tumours (glioma: OR 0.98 [95 % CI 0.76–1.26]; meningioma: OR 0.83 [95 % CI 0.61–1.14]; acoustic neuroma: OR 0.76 [95 % CI 0.52–1.11] for regular users up to one year before diagnosis; OR 0.83 [95 % CI 0.58–1.19] for regular users up to five years before diagnosis).

Cumulative number of calls

There was no dose-response trend with respect to the cumulative number of phone calls for an elevated risk for all three tumour types. Even in the upper decile of cumulative number of calls (> 27,000 calls) there was no elevated risk, compared to non-exposed participants (glioma: OR 0.98 [95 % CI 0.76–1.26]; meningioma: OR 0.83 [95 % CI 0.61–1.14]; acoustic neuroma: OR 0.93 [95 % CI 0.61–1.41] for regular users up to one year; OR 1.55 [95 % CI 0.84–2.86] for regular users up to five years).

Cumulative call time

In the upper decile of the recalled cumulative call time, corresponding to at least 1,640 hours, the ORs were elevated for glioma (OR 1.40 [95 % CI 1.03–1.89]) and acoustic neuroma (only in regular users up to five years: OR 2.79 [95 % CI 1.51–5.16]). A closer examination of these risk estimates revealed that the elevated OR for glioma was found only in the short-term users (start of phone use 1-4 years before the diagnosis): OR 3.77 [95% CI 1.25–11.4]. For acoustic neuroma, on the contrary, the elevated risk was only found in long-term users (start of phone use ≥ 10 years before diagnosis): OR 1.93 [95 % 1.10–3.38].

Sixty subjects reported rather implausible values of call time (five or more hours per day). When they were excluded from the analyses, the OR for glioma decreased and was no longer statistically significant. Only in regular users up to five years the elevated OR was still observed for acoustic neuroma (OR 2.86 [95 % CI: 1.39–5.92]).

Tumour localization

ORs for glioma tended to be greater in the temporal lobe than in other lobes of the brain, but the CIs around the lobe-specific estimates were wide.

ORs for glioma and acoustic neuroma were elevated in subjects who reported usual mobile phone use on the same side of the head as their tumour, but only in the upper decile with the cumulative call time ≥1,640 hours: OR for glioma 1.96 [95 % CI 1.22–3.16], for acoustic neuroma OR = 2.33 [95 % CI 1.23–4.40] in regular users up to one year, OR = 3.53 [95 % CI 1.59–7.82] in regular users up to five years.

A further analysis in 792 regular mobile phone users with glioma diagnosis showed a positive association of tumour localization with self-reported preferred head side. However, this association did not differ by the cumulative call time or the number of calls and was also observed among persons who had used their mobile phone for less than 200 hours. Also, the distance of the tumour to the closest ear was similar in regular mobile phone users and non-users. The cases were frequently aware of their tumour location, and it is possible that they have overestimated the use of mobile phone on the side of the tumour when assessing it retrospectively.

Investigation of possible sources of bias

A potential source of bias in the INTERPHONE study is that the control subjects were frequently interviewed later in time than the cases. With the rapid spread of mobile phone use, control subjects who were interviewed later might have reported higher mobile phone usage than cases who had been interviewed earlier. In an analysis with five INTERPHONE country databases, cases and controls were rematched by the time of the interview to assess the extent of bias. The findings were very similar to the main results. Protective effects became less protective and the increased risk among long-term users and among those in the highest categories of the cumulative call time and cumulative number of calls became stronger.

Conclusions

This is the largest study of the risk of brain tumours in relation to mobile phone use conducted to date which includes substantial numbers of subjects who had used mobile phones for ten years or longer. Overall, no increase in risk of glioma, meningioma or acoustic neuroma was observed with use of mobile phones. There were suggestions of an increased risk of glioma and acoustic neuroma at the highest exposure levels, but biases and error prevent a causal interpretation.

The subjects of the INTERPHONE study were adults; therefore nothing could be said about the risk of mobile phone use amongst children and teenagers. The majority of mobile phone users in the study were not heavy users by today’s standards. Mobile phone usage has become much more prevalent. Today it is not unusual for teenagers and young adults to use a mobile phone for an hour a day or even more. The possible effects of long-term heavy use of mobile phones require further investigation, especially for those subjects who started frequent use with young ages.

References

INTERPHONE Study Group. Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study. Int J Epidemiol 2010 Jun; 39(3):675-94.

INTERPHONE Study Group. Acoustic neuroma risk in relation to mobile telephone use: results of the INTERPHONE international case-control study. Cancer Epidemiol 2011 Oct; 35(5):453-64.

Swerdlow AJ, Feychting M, Green AC, Leeka Kheifets LK, Savitz DA, and International Commission for Non-Ionizing Radiation Protection Standing Committee on Epidemiology. Mobile phones, brain tumors, and the interphone study: where are we now? Environmental health perspectives. 2011;119(11):1534-8.

Turner MC, Sadetzki S, Langer CE, Villegas PR, Figuerola J, Armstrong BK, et al. Investigation of bias related to differences between case and control interview dates in five INTERPHONE countries. Annals of epidemiology. 2016;26(12):827-32.e2.

Grell K, Frederiksen K, Schuz J, Cardis E, Armstrong B, Siemiatycki J, et al. The Intracranial Distribution of Gliomas in Relation to Exposure From Mobile Phones: Analyses From the INTERPHONE Study. American journal of epidemiology. 2016;184(11):818-28.