Most studies of association between cancer and mobile phone use have evaluated the risk of brain tumors and acoustic neuromas (), although in a few instances the risks of other tumors have been explored. Also studies of symptoms in relation to mobile phone use have been conducted (). The first case–control study of brain tumors was conducted in Sweden (Hardell et al. 1999
) and included adult cases diagnosed in two regions in Sweden between 1994 and 1996 and still alive, with two controls per case matched for region of residence. Details of intensity and duration of mobile phone use, preferred side (ear) of use, and whether phones were analog or digital, and handheld or hands-free, were gathered by postal questionnaire followed by telephone interview (Hardell et al. 1999
). A total of 209 cases [about one-third of the malignant cases occurring in the study geographical area in the period (Ahlbom and Feychting 1999
)] took part along with 425 controls (a reported 91% response rate—extraordinarily high for a contemporary population-based study). Originally no association of phone use with brain tumors was found (Hardell et al. 1999
), although later reanalysis of side of use in relation to tumor site suggested a possible relationship (Hardell et al. 2001
). A second larger study a few years later by the same authors (Hardell et al. 2002
) was similar in design to the first. It involved 1,303 living cases (half of all brain tumors diagnosed 1997–2000) and their controls. Cumulative phone use for > 85 hr, 10 years before case diagnosis, gave ORs for brain tumors of 1.9 (95% CI, 1.1–3.2) and 3.0 (95% CI, 0.6–14.9), respectively, for analog and cordless phones, but ORs were not increased for digital phones. There was no adjustment for confounding variables. Ipsilateral use of analog phones was related to temporal tumors [OR = 2.5 (95% CI, 1.3–4.9)], and analog phone use was associated with acoustic neuroma [OR = 3.5 (95% CI, 1.8–6.8)] (Hardell et al. 2002
Summary of studies of mobile phone use and risk of brain tumors.
Summary of studies of mobile phone use and symptoms.
Muscat et al. conducted two hospital-based case–control studies in the United States, one of malignant brain tumors (Muscat et al. 2000
), the other of acoustic neuroma (Muscat et al. 2002
), both using the same ascertainment and data collection procedures (). The first study included 469 cases of brain cancer (70% response rate) and 422 matched controls with a variety of malignant and benign conditions from the same hospitals (90% response rate). Information about mobile phone use was obtained by standard interview (of proxies for 9% of cases and 1% of controls). No increased risks were seen relating to frequency or duration of use, or for site or histologic subtype of brain cancer. An excess of brain cancer was found on the same side of the head as reported phone use among 41 cases with assessable data (p
= 0.06), compared with a deficit on the side of mobile phone use for tumors specifically located in the temporal lobe (p
= 0.33). In the acoustic neuroma study, 90 cases were compared with 86 controls, and no associations were seen with level or laterality of phone use.
In another U.S. hospital-based case–control study (Inskip et al. 2001
), interview data were obtained from 782 cases with brain tumors (92% response rate; via proxies for 16% and 3% of glioma and acoustic neuroma patients, respectively) and 799 matched hospital controls with nonmalignant conditions (88% response; 3% by proxy). Results adjusted for potential confounders showed no association between cumulative use of mobile phones (mainly analog) and brain tumor overall or by histologic subtype or anatomical location.
Subscription records of national network providers were used to characterize mobile phone users in a Finnish case–control study (Auvinen et al. 2002
). All people (398) diagnosed with brain tumors in 1996, ascertained from the National Cancer Registry, were matched with five controls per case drawn from the national population register (). The OR for brain tumors with ever-subscribed to phones was 2.1 (95% CI, 1.3–3.4) for analog phones and 1.0 for digital, and the OR for glioma was 1.5 (95% CI, 1.0–2.4) for any phone subscription. The average duration of subscription was 2–3 years for analog phones and less for digital. Adjusting for potential confounders did not alter results. No information was available about the frequency or duration of calls or about corporate subscriptions.
Of two cohort studies, an early U.S. study (Dreyer et al. 1999
; Rothman et al. 1996
) analyzed 1-year of follow-up of mortality in a cohort of 285,561 noncorporate users of mobile phones with at least two billing cycles from two U.S. carriers. Mortality was ascertained from the National Death Index. No relation was found between mortality from brain cancer and the use of handheld versus hands-free phones, based on only six cases. The overall mortality of the cohort was less that in the general population. The second cohort study was in Denmark (Johansen et al. 2002b
) and included 420,095 private cellular network subscribers (80% of all subscribers), with average follow-up for analog and digital subscribers of 3.5 and 1.9 years, respectively. SIRs comparing cancer rates in phone users with national rates allowing for sex, age, and period showed no relation to risk of brain and nervous system cancers [SIR 0.95 (95% CI, 0.81–1.2)] and reduced risk of smoking-related cancers. Risks did not vary by age at, or time since, first subscription, phone type, or tumor location. Again, no information was available about the frequency or duration of calls or about corporate subscriptions.
Regarding other head and neck cancers, no association with parotid gland tumors (34 cases) was seen in the Finnish case–control study (Auvinen et al. 2002
) or in the Danish cohort study (Johansen et al. 2002b
). A mixed population and hospital-based case–control study of uveal melanoma (Stang et al. 2001
) included 118 cases and 475 controls. Occupational exposure to mobile phones for several hours a day for ≥ 6 months assessed by interview gave an increased OR [4.2 (95% CI, 1.2–15)], reflecting the result in the hospital-based participants (OR = 10). There was no increased risk of uveal melanoma, however, in the Danish mobile phone user cohort (Johansen et al. 2002a
). Finally, leukemia was assessed in both cohort studies, but no relation with phone use was found.
The first report from the multicenter Interphone study, a very large, international case–control study, has recently been published. This report from the Danish component focused on acoustic neuroma and was negative; however, the number of long-term users was small (Christensen et al. 2004
Subjective symptoms, including tinnitus, headache, dizziness, fatigue, sensations of warmth, dysesthesia of the scalp, visual symptoms (e.g., flashes), memory loss, and sleep disturbance have been investigated in relation to mobile phone use (Chia et al. 2000
; Oftedal et al. 2000
; Sandstrom et al. 2001
; details provided in ). As discussed above in relation to transmitter studies, such research is highly susceptible to recall bias, and for completeness we have added , which includes experimental studies on mobile phone use and symptoms.
Summary of experimental studies of mobile phone use and symptoms.
Handheld mobile phones were not used regularly until the 1990s, so published studies at present can only assess relatively short lag periods before cancer manifestation. The relevant lag periods are unknown. Furthermore, even in the large Danish study (Johansen et al. 2002b
), long-term (15 years) subscribers to analog phones comprised only a small proportion of users.
Another issue relates to choice of study population. No study populations to date have included children, yet children are increasingly heavy users of mobile phones and they are potentially highly susceptible to harmful effects (although some of these effects might not manifest until adulthood). So far, study populations have been ascertained from population registers in Nordic studies, hospital in-patients in U.S. case–control studies, and cellular network private subscribers in the two cohort studies and the Finnish study (). Although the population-based studies should have avoided the selection biases inherent in the hospital based studies, this was not so in population-based case–control studies of prevalent living cases with low participation rates (Hardell et al. 1999
) because, inter alia, those with high-grade tumors tend to be excluded. Although rapid recruitment of incident brain tumor cases was facilitated in the hospital-based studies, loss due to death was still greater for malignant than benign tumors as reflected in differential proxy response rates by tumor type (Inskip et al. 2001
), and there is a weakness in using hospital controls with a variety of conditions of unknown relationship to mobile phone use.
Differential recall of mobile phone use among those with and without a cerebral tumor in case–control studies is a major potential source of bias, exacerbated by differential timing of data collection from cases and controls in the hospital studies. Reporting bias is also likely because presence of a brain tumor may distort both memory and hearing and because the use of proxy respondents was more common for cases than controls. Relying on private cellular network subscription as a measure of mobile phone use would also have resulted in substantial misclassification because subscribers bear only a modest relation to users (Funch et al. 1996
) and because corporate users were either excluded or included in the unexposed group. Until there is some objective measure of RF exposure, or at least validation of self-reported records, the validity of self-reported indices of phone use [e.g., average minutes of use per day (Hardell et al. 2002
; Inskip et al. 2001
) or minutes or hours per month as indicators of RF exposure] remains unknown.
Overall, although occasional significant associations between various types of brain tumors and analog mobile phone use have emerged (often seen after multiple testing), no single association has been consistently reported across population-based studies. The timing of epidemiologic studies and the lack of knowledge about actual RF exposure to the brain from mobile phone use to date (Ghandi et al. 1999
) militate strongly against current ability to detect any true association. Thus current evidence is inconclusive regarding cancer risk after heavy RF exposure from mobile phones. Similarly, the studies of symptoms to date do not suggest that a single exposure to RFs from a mobile phone results in immediately identifiable symptoms, but there are no adequate data available about the symptomatic effects of mobile phone use, especially among people who claim hypersensitivity to RFs.