Isabelle Deltour

The INTERPHONE study: design, epidemiological methods, and description of the study population

The very rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. A multinational case–control study, INTERPHONE, was set-up to investigate whether mobile phone use increases the risk of cancer and, more specifically, whether the RF fields emitted by mobile phones are carcinogenic. The study focused on tumours arising in the tissues most exposed to RF fields from mobile phones: glioma, meningioma, acoustic neurinoma and parotid gland tumours. In addition to a detailed history of mobile phone use, information was collected on a number of known and potential risk factors for these tumours. The study was conducted in 13 countries. Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the UK using a common core protocol. This paper describes the study design and methods and the main characteristics of the study population. INTERPHONE is the largest case–control study to date investigating risks related to mobile phone use and to other potential risk factors for the tumours of interest and includes 2,765 glioma, 2,425 meningioma, 1,121 acoustic neurinoma, 109 malignant parotid gland tumour cases and 7,658 controls. Particular attention was paid to estimating the amount and direction of potential recall and participation biases and their impact on the study results.

Validation of short term recall of mobile phone use for the Interphone study

Aim: To validate short term recall of mobile phone use within Interphone, an international collaborative case control study of tumours of the brain, acoustic nerve, and salivary glands related to mobile telephone use. Methods: Mobile phone use of 672 volunteers in 11 countries was recorded by operators or through the use of software modified phones, and compared to use recalled six months later using the Interphone study questionnaire. Agreement between recalled and actual phone use was analysed using both categorical and continuous measures of number and duration of phone calls. Results: Correlations between recalled and actual phone use were moderate to high (ranging from 0.5 to 0.8 across countries) and of the same order for number and duration of calls. The kappa statistic demonstrated fair to moderate agreement for both number and duration of calls (weighted kappa ranging from 0.20 to 0.60 across countries). On average, subjects underestimated the number of calls per month (geometric mean ratio of recalled to actual = 0.92, 95% CI 0.85 to 0.99), whereas duration of calls was overestimated (geometric mean ratio = 1.42, 95% CI 1.29 to 1.56). The ratio of recalled to actual use increased with level of use, showing underestimation in light users and overestimation in heavy users. There was substantial heterogeneity in this ratio between countries. Inter-individual variation was also large, and increased with level of use. Conclusions: Volunteer subjects recalled their recent phone use with moderate systematic error and substantial random error. This large random error can be expected to reduce the power of the Interphone study to detect an increase in risk of brain, acoustic nerve, and parotid gland tumours with increasing mobile phone use, if one exists.

Distribution of RF energy emitted by mobile phones in anatomical structures of the brain

The rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in possible carcinogenic effects of radio frequency (RF). Because exposure to RF from phones is localized, if a risk exists it is likely to be greatest for tumours in regions with greatest energy absorption. The objective of the current paper was to characterize the spatial distribution of RF energy in the brain, using results of measurements made in two laboratories on 110 phones used in Europe or Japan. Most (97-99% depending on frequency) appears to be absorbed in the brain hemisphere on the side where the phone is used, mainly (50-60%) in the temporal lobe. The average relative SAR is highest in the temporal lobe (6-15%, depending on frequency, of the spatial peak SAR in the most exposed region of the brain) and the cerebellum (2-10%) and decreases very rapidly with increasing depth, particularly at higher frequencies. The SAR distribution appears to be fairly similar across phone models, between older and newer phones and between phones with different antenna types and positions. Analyses of risk by location of tumour are therefore important for the interpretation of results of studies of brain tumours in relation to mobile phone use.

Recall bias in the assessment of exposure to mobile phones

Most studies of mobile phone use are case–control studies that rely on participants’ reports of past phone use for their exposure assessment. Differential errors in recalled phone use are a major concern in such studies. INTERPHONE, a multinational case–control study of brain tumour risk and mobile phone use, included validation studies to quantify such errors and evaluate the potential for recall bias. Mobile phone records of 212 cases and 296 controls were collected from network operators in three INTERPHONE countries over an average of 2 years, and compared with mobile phone use reported at interview. The ratio of reported to recorded phone use was analysed as measure of agreement. Mean ratios were virtually the same for cases and controls: both underestimated number of calls by a factor of 0.81 and overestimated call duration by a factor of 1.4. For cases, but not controls, ratios increased with increasing time before the interview; however, these trends were based on few subjects with long-term data. Ratios increased by level of use. Random recall errors were large. In conclusion, there was little evidence for differential recall errors overall or in recent time periods. However, apparent overestimation by cases in more distant time periods could cause positive bias in estimates of disease risk associated with mobile phone use.

Time Trends in Brain Tumor Incidence Rates in Denmark, Finland, Norway, and Sweden, 1974–2003

In Denmark, Finland, Norway, and Sweden, the use of mobile phones increased sharply in the mid-1990s; thus, time trends in brain tumor incidence after 1998 may provide information about possible tumor risks associated with mobile phone use. We investigated time trends in the incidence of glioma and meningioma in Denmark, Finland, Norway, and Sweden from 1974 to 2003, using data from national cancer registries. We used joinpoint regression models to analyze the annual incidence rates of glioma and meningioma. During this period, 59,984 men and women aged 20-79 years were diagnosed with brain tumors in a population of 16 million adults. All statistical tests were two-sided. From 1974 to 2003, the incidence rate of glioma increased by 0.5% per year (95% confidence interval [CI] = 0.2% to 0.8%) among men and by 0.2% per year (95% CI = -0.1% to 0.5%) among women and that of meningioma increased by 0.8% per year (95% CI = 0.4% to 1.3%) among men, and after the early 1990s, by 3.8% per year (95% CI = 3.2% to 4.4%) among women. No change in incidence trends were observed from 1998 to 2003, the time when possible associations between mobile phone use and cancer risk would be informative about an induction period of 5-10 years.

Acoustic neuroma risk in relation to mobile telephone use: Results of the INTERPHONE international case-control study

BACKGROUND The rapid increase in mobile telephone use has generated concern about possible health risks of radiofrequency electromagnetic fields from these devices. METHODS A case-control study of 1105 patients with newly diagnosed acoustic neuroma (vestibular schwannoma) and 2145 controls was conducted in 13 countries using a common protocol. Past mobile phone use was assessed by personal interview. In the primary analysis, exposure time was censored at one year before the reference date (date of diagnosis for cases and date of diagnosis of the matched case for controls); analyses censoring exposure at five years before the reference date were also done to allow for a possible longer latent period. RESULTS The odds ratio (OR) of acoustic neuroma with ever having been a regular mobile phone user was 0.85 (95% confidence interval 0.69-1.04). The OR for ≥10 years after first regular mobile phone use was 0.76 (0.52-1.11). There was no trend of increasing ORs with increasing cumulative call time or cumulative number of calls, with the lowest OR (0.48 (0.30-0.78)) observed in the 9th decile of cumulative call time. In the 10th decile (≥1640 h) of cumulative call time, the OR was 1.32 (0.88-1.97); there were, however, implausible values of reported use in those with ≥1640 h of accumulated mobile phone use. With censoring at 5 years before the reference date the OR for ≥10 years after first regular mobile phone use was 0.83 (0.58-1.19) and for ≥1640 h of cumulative call time it was 2.79 (1.51-5.16), but again with no trend in the lower nine deciles and with the lowest OR in the 9th decile. In general, ORs were not greater in subjects who reported usual phone use on the same side of the head as their tumour than in those who reported it on the opposite side, but it was greater in those in the 10th decile of cumulative hours of use. CONCLUSIONS There was no increase in risk of acoustic neuroma with ever regular use of a mobile phone or for users who began regular use 10 years or more before the reference date. Elevated odds ratios observed at the highest level of cumulative call time could be due to chance, reporting bias or a causal effect. As acoustic neuroma is usually a slowly growing tumour, the interval between introduction of mobile phones and occurrence of the tumour might have been too short to observe an effect, if there is one.

The effects of recall errors and of selection bias in epidemiologic studies of mobile phone use and cancer risk

This paper examines the effects of systematic and random errors in recall and of selection bias in case–control studies of mobile phone use and cancer. These sensitivity analyses are based on Monte–Carlo computer simulations and were carried out within the INTERPHONE Study, an international collaborative case–control study in 13 countries. Recall error scenarios simulated plausible values of random and systematic, non-differential and differential recall errors in amount of mobile phone use reported by study subjects. Plausible values for the recall error were obtained from validation studies. Selection bias scenarios assumed varying selection probabilities for cases and controls, mobile phone users, and non-users. Where possible these selection probabilities were based on existing information from non-respondents in INTERPHONE. Simulations used exposure distributions based on existing INTERPHONE data and assumed varying levels of the true risk of brain cancer related to mobile phone use. Results suggest that random recall errors of plausible levels can lead to a large underestimation in the risk of brain cancer associated with mobile phone use. Random errors were found to have larger impact than plausible systematic errors. Differential errors in recall had very little additional impact in the presence of large random errors. Selection bias resulting from underselection of unexposed controls led to J-shaped exposure–response patterns, with risk apparently decreasing at low to moderate exposure levels. The present results, in conjunction with those of the validation studies conducted within the INTERPHONE study, will play an important role in the interpretation of existing and future case–control studies of mobile phone use and cancer risk, including the INTERPHONE study.

Effect of Internet peer-support groups on psychosocial adjustment to cancer: a randomised study.

Background:We conducted a randomised study to investigate whether providing a self-guided Internet support group to cancer patients affected mood disturbance and adjustment to cancer.Methods:Baseline and 1-, 6- and 12-month assessments were conducted from 2004 to 2006 at a national rehabilitation centre in Denmark. A total of 58 rehabilitation course weeks including 921 survivors of various cancers were randomly assigned to a control or an intervention group by cluster randomisation. The intervention was a lecture on the use of the Internet for support and information followed by participation in an Internet support group. Outcome measures included self-reported mood disturbance, adjustment to cancer and self-rated health. Differences in scores were compared between the control group and the intervention group.Results:The effect of the intervention on mood disturbance and adjustment to cancer showed a transient difference at the 6-month follow-up, where the intervention group reported less reduction in anxious preoccupation (P=0.04), helplessness (P=0.002), confusion (P=0.001) and depression (P=0.04). Otherwise no significant effects were observed.Conclusion:We conclude that use of Internet-based support groups in cancer patients still needs to confirm long-lasting psychological effects.

Quantifying the Impact of Selection Bias Caused by Nonparticipation in a Case–Control Study of Mobile Phone Use

PURPOSE To quantitatively assess the impact of selection bias caused by nonparticipation in a multinational case-control study of mobile phone use and brain tumor. METHODS Non-response questionnaires (NRQ) were completed by a sub-set of nonparticipants. Selection bias factors were calculated based on the prevalence of mobile phone use reported by nonparticipants with NRQ data, and on scenarios of hypothetical exposure prevalence for other nonparticipants. RESULTS Regular mobile phone use was reported less frequently by controls and cases who completed the NRQ (controls, 56%; cases, 50%) than by those who completed the full interview (controls, 69%; cases, 66%). This relationship was consistent across study centers, sex, and age groups. Lower education and more recent start of mobile phone use were associated with refusal to participate. Bias factors varied between 0.87 and 0.92 in the most plausible scenarios. CONCLUSIONS Refusal to participate in brain tumor case-control studies seems to be related to less prevalent use of mobile phones, and this could result in a downward bias of around 10% in odds ratios for regular mobile phone use. The use of simple selection bias estimation methods in case-control studies can give important insights into the extent of any bias, even when nonparticipant information is incomplete.

Determinants of mobile phone output power in a multinational study: implications for exposure assessment

Objectives: The output power of a mobile phone is directly related to its radiofrequency (RF) electromagnetic field strength, and may theoretically vary substantially in different networks and phone use circumstances due to power control technologies. To improve indices of RF exposure for epidemiological studies, we assessed determinants of mobile phone output power in a multinational study. Methods: More than 500 volunteers in 12 countries used Global System for Mobile communications software-modified phones (GSM SMPs) for approximately 1 month each. The SMPs recorded date, time, and duration of each call, and the frequency band and output power at fixed sampling intervals throughout each call. Questionnaires provided information on the typical circumstances of an individual’s phone use. Linear regression models were used to analyse the influence of possible explanatory variables on the average output power and the percentage call time at maximum power for each call. Results: Measurements of over 60 000 phone calls showed that the average output power was approximately 50% of the maximum, and that output power varied by a factor of up to 2 to 3 between study centres and network operators. Maximum power was used during a considerable proportion of call time (39% on average). Output power decreased with increasing call duration, but showed little variation in relation to reported frequency of use while in a moving vehicle or inside buildings. Higher output powers for rural compared with urban use of the SMP were observed principally in Sweden where the study covered very sparsely populated areas. Conclusions: Average power levels are substantially higher than the minimum levels theoretically achievable in GSM networks. Exposure indices could be improved by accounting for average power levels of different telecommunications systems. There appears to be little value in gathering information on circumstances of phone use other than use in very sparsely populated regions.