Review and Cancer Michael Kundi The Controversy about a Possible Relationship between Mobile Phone Use Institute of Environmental Health, Medical University of Vienna, Vienna, Austria o Bvitcej : During the last decade, mobile phone use increased to almost 100% prevalence in many countries of the world. Evidence for potential health hazards accumulated in parallel by epidemiologic investigations has raised controversies about the appropriate interpretation and the degree of bias and confounding responsible for reduced or increased risk estimates. ecruos d ta : Overall, I identified 33 epidemiologic studies in the peer-reviewed literature, most of which (25) were about brain tumors. Two groups have collected data for ≥ 10 years of mobile phone use: Hardell and colleagues from Sweden and the Interphone group, an international consortium from 13 countries coordinated by the International Agency for Research on Cancer. synthei c onclusi d at : Combined odds ratios (95% confidence intervals) from these studies for glioma, acoustic neuroma, and meningioma were 1.5 (1.2–1.8); 1.3 (0.95–1.9); and 1.1 (0.8–1.4), respectively. : Methodologic considerations revealed that three important conditions for epidemio- logic studies to detect an increased risk are not met: a) no evidence-based exposure metric is avail- able; b) the observed duration of mobile phone use is generally still too low; c) no evidence-based selection of end points among the grossly different types of neoplasias is possible because of lack of etiologic hypotheses. Concerning risk estimates, selection bias, misclassification bias, and effects of the disease on mobile phone use could have reduced estimates, and recall bias may have led to spuri- ously increased risks. The overall evidence speaks in favor of an increased risk, but its magnitude cannot be assessed at present because of insufficient information on long-term use. k ey words : acoustic neuroma, brain tumors, causation, epidemiology, glioma, meningioma, mobile phones, risk assessment. Environ Health Perspect 117:316–324 (2009). doi:10.1289/ ehp.11902 available via http://dx.doi.org/ [Online 26 September 2008] Because of the enormous increase in mobile phone use starting in the mid-1990s and reaching almost 100% prevalence in many countries worldwide by now, concerns have been raised that even small risks for developing chronic diseases such as cancer from mobile phone use may have substantial impact on public health. In fact, never before in history has any device of comparative prevalent use been associated with such high exposure to high-frequency electromagnetic fields (EMFs). (In addition, exposure to extremely low-fre- quency magnetic fields occurs from battery discharge.) Although from the perspective of the thermal effects paradigm, the rate of energy deposition in tissues of the mobile phone user is below levels considered harmful, there has been debate since the 1930s that tissue heating may not be the only relevant effect elicited by exposure to high-frequency EMFs; thus, there may be a relevant risk that has not been estab- lished yet because of the scarcity of exposure conditions that are comparable across a signifi- cant proportion of the population. For all the diverse high-frequency exposures occurring in environmental and occupational settings ranging from long-waves [a type of amplitude modulation (AM) broadcasting with carrier frequencies between 153 and 280 kHz] to radar waves, only a few long-term observa- tional studies have been published (for an over- view, see Ahlbom et al. 2004; Krewski et al. 2001; Kundi et al. 2004). Similarly scarce are long-term animal studies of low-level exposures 316 in the pre–mobile phone era. Hence, at the time mobile phones were introduced, there were insufficient data to decide about health risks from low-level exposures, but the pre- vailing opinion that no relevant health effects occur at exposures below guideline levels led to the expectation that mobile phones are safe. However, the exponential growth of mobile phone use came as a surprise to the indus- try as well as to scientists involved in EMF risk assessment. Therefore, the existing gaps in knowledge should be addressed in both experimental as well as epidemiologic inves- tigations focusing on exposures occurring in mobile telecommunications. Since the mid-1990s, many epidemio- logic studies of mobile phone use have been conducted worldwide, most of them focusing on tumors of the head region. Despite the growing database, the concerns have not been settled and a controversy still exists about pos- sible adverse health effects. Although some may be inclined to attribute the ongoing debate to the enormous economic impact of modern telecommunication during the past decade, this debate also mirrors fundamental difficulties and a permissible range of inter- pretation under circumstances of insufficient knowledge. Despite this state of affairs, not all arguments that have been put forward in this controversy are valid. In the following sections I will concentrate on epidemiologic findings and their interpretation, although experimen- tal work deserves similar critical appraisal. I will first give a brief overview of the results of epidemiologic investigations of mobile phone use and tumors of the head region. I will then address methodologic problems associated with these studies and, by application of the pragmatic approach pro- posed earlier (Kundi 2006), discuss whether epidemiologic evidence supports a causal inter- pretation of an association between mobile phone use and brain tumors. Overview of Epidemiologic Studies Table 1 presents an overview of results of epi- demiologic studies on the association between brain tumors and mobile phone use. Other end points include salivary gland tumors (Hardell et al. 2004; Lönn et al. 2006; Sadetzki et al. 2008), uveal melanoma (Stang et al. 2001), non-Hodgkin lymphoma (Hardell et al. 2005c; Linet et al. 2006), facial nerve tumors (Warren et al. 2003), and testicular cancer (Hardell et al. 2007), but for these diseases the database is insufficient to date. Except for the early cohort study from the United States (Dreyer et al. 1999) that was stopped by the court after 1 year of follow-up and the Danish retrospective cohort study (Johansen et al. 2001; Schüz et al. 2006b), all investigations have been case–control studies. The “Overall results” from 25 epidemio- logic studies listed in Table 1 do not demon- strate support for an increased risk. Only a few risk estimates are significantly elevated, and some are even significantly reduced. Risk esti- mates for longer duration of use are higher, on average, than overall estimates, and estimates for ipsilateral mobile phone use (i.e., use of the mobile phone on the same side where the tumor occurred), where available, tend to be even higher. Implications of these findings are discussed below. Methodologic Problems Although a number of established study designs in epidemiology have been success- fully applied in thousands of investigations in the past 50 years, perhaps few epidemiologists are fully aware of the conditions necessary Address correspondence to M. Kundi, Institute of Environmental Health, Medical University of Vienna, Kinderspitalgasse 15, 1095 Vienna, Austria. Telephone: 43 1 4277 64726. Fax: 43 1 4277 9647. E-mail: michael.kundi@meduniwien.ac.at The author declares he has no competing financial interests. Received 7 July 2008; accepted 26 September 2008. ovlume 117 | number 3 | March 2009 • Environmental Health Perspectives