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3.3.2 Cancer

Studies on cancer in relation to mobile telephony have focused on intracranial tumours because deposition of energy from RF fields from a mobile phone is mainly within a small area of the skull near the handset. When whole body exposure is considered, as in some occupational and environmental studies, also other forms of cancer have been investigated.

3.3.2.1. Epidemiology

What was already known on this subject?

At the time of the previous CSTEE opinion of 2001, most epidemiological studies on exposure to RF fields had examined exposures at the workplace. The overall evidence did not suggest consistent cancer excesses. With regard to mobile phones, only few studies were available at the time of the previous opinion and the short exposure period in these studies did not allow any firm conclusions. The few studies on residential exposure to RF fields from transmitters had serious methodological limitations.

What has been achieved since then?

In total, about 30 papers of original studies on mobile phone use and cancer were published in the last five years. Results are summarized in Table 2 for brain tumours and in Table 3 for acoustic neuroma. All but one study were case-control studies, mostly on brain tumours, some on salivary gland tumours or uveal melanoma. One was a large cohort study of all Danish mobile phone subscribers between 1982 and 1995 who were followed up for a variety of cancers; no increased risk for any cancer was observed but follow up time was short (Johansen et al. 2001). A recent update of the cohort study with an average follow up time of 8.5 years yielded 14,249 cancer cases observed in the cohort versus 15,001 expected cases based on cancer rates observed in the rest of the Danish adult population (Schüz et al. 2006b). The deficit was mainly attributable to smoking-related cancers, suggesting a healthy cohort effect. The overall relative risk estimates for brain tumours and leukaemia were close to one, however, only 28 brain tumour cases occurred in subscribers of a mobile phone of 10 years or more, whereas 42.5 cases were expected.

The Interphone study is a multinational case-control study coordinated by the International Agency for Research on Cancer (IARC). It is a population-based study with prospective ascertainment of incident cases and face-to-face interviews for exposure assessment. With regard to brain tumours, results from the first four components of the Interphone study suggest no risk increase for meningioma or glioma. This is consistently so among subjects with less than 10 years of use. For regular mobile phone users of 10 years or more, no indications of risk increases were seen in three out of four components, namely in Sweden (Lönn et al. 2005), Denmark (Christensen et al. 2005) and the UK (Hepworth et al. 2006), but the German component does reveal a somewhat raised relative risk estimate for glioma (Schüz et al. 2006a). This increase, however, is based on small numbers and due to the wide confidence interval the result is not in contradiction with the other Interphone components.

In contrast, a Swedish group not participating in the Interphone-study, conducting several case-control studies using self-administered questionnaires for exposure assessment, has repeatedly observed increased relative risk estimates for brain tumours. In 2006, the group revisited their previously published studies and reported statistically significant risk increases for both analogue and digital mobile phones as well as cordless phones already after one year of use (Hardell et al. 2006). After ten years of use they observed about a doubling of the relative risk estimates, with the strongest increase for high grade glioma.

Acoustic neuromas, benign tumours that develop very slowly, arise from the Schwann cells, which enfold the vestibulocochlear nerve (VIII. cranial nerve). They are of particular interest because of their location. The Hardell-group from Sweden has in several studies reported raised relative risk estimates for acoustic neuroma, also with very short induction periods (Hardell et al. 2005b). Three of the Interphone components, Denmark, Sweden, and Japan, have reported their country specific acoustic neuroma results (Christensen et al. 2004, Lönn et al. 2004, Takebayashi et al. 2006). Lönn et al. (2004) reported a doubling of the relative risk estimate after ten years of regular mobile phone use compared to subjects who never used a mobile phone regularly. This association became stronger when the analysis was restricted to preferred phone use at the same side as the tumour. Christensen’s and Takebayashi’s results did not support this, but they were based on fewer long-term users. Five of thirteen countries of the Interphone study (including Denmark, Finland, Norway, Sweden, and the UK) were pooled for a joint analysis to examine the association between mobile phone use and risk of acoustic neuroma (Schoemaker et al. 2005). While no overall association was seen among all long-term users (see Table 3), the data suggest that there may be an increased risk when the preferred side of the head of use is considered in the analysis. For 10+ years of use of mobile phones, the relative risk for acoustic neuroma at the preferred side of use was 1.8 (95%-CI 1.1-3.1). Because of methodological inter-study differences it would have been of considerable interest to compare the results across the six studies, but small numbers in most of the centres preclude that analysis.

All those studies are facing limitations in their exposure assessment, which was either a list of subscribers from the operators or self-reported mobile phone use. While the first method is an objective measure, it has limitations because subscription predicts use of a mobile phone only to some extent. Recent validation studies in volunteers comparing current self-reported use with traffic records from network operators show a moderate agreement, but it cannot be excluded that agreement is worse with respect to past mobile phone use or among patients with brain tumours (Vrijheid et al. 2006). Especially patients with high stage glioma showed some memory performance problems in the Danish Interphone study (Christensen et al. 2005). What seems to be reassuring despite these shortcomings is, that once the amount of mobile phone use is estimated with some validity, this is a satisfactory proxy for RF field exposure from these devices, as was shown in studies recording output power of mobile phones during operation (Berg et al. 2005). Laterality (side) of use is not easy to obtain in a retrospective study, as early symptoms may affect the side of use. Although some results are now available for long- term users, their numbers are still small and the results of the whole Interphone dataset should be awaited before drawing conclusions.

No striking new results appeared for studies on occupational and residential RF fields exposures since the previous opinion. While some positive associations have been reported from occupational studies, the overall picture is far from clear (Ahlbom et al. 2004). Many studies lack individual exposure assessment and only job titles or branches were used as exposure proxies. Studies on exposure from transmitters are limited by crude exposure measures and small numbers of exposed subjects, and the ecological nature of most studies.

Discussion

Mobile phones in relation to health are now being studied with great effort and in comprehensive studies, particularly in the Interphone Study. The results of the Interphone Study will soon become available. It has to be doubted, however, that the results will be entirely conclusive, as the first results from published national components of this study already raise a number of questions with respect to the potential of bias. Another limitation is that also in the current studies, long-term mobile phone users have had hardly more than 10 years of regular use of mobile phones, which still may be a relatively short latency period, particularly for slowly growing benign tumours. Among those long-term users, most were initially users of analogue mobile phone and thus, the number of long-term users of the digital technology is even smaller. Prospective long term follow up studies overcome both the limitations of retrospective exposure assessment and the latency problem and are recommended as a powerful long-term surveillance system for a variety of potential endpoints, including cancer, to fill current gaps in knowledge.