Gabriele Berg

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.

Helicobacter pylori infection and serum ferritin: A population-based study among 1806 adults in Germany.

OBJECTIVE:Helicobacter pylori may possibly affect the iron metabolism by occult bleeding, impaired absorption of nonhem iron, and by scavenging hem iron or ferritin, as some studies have suggested. The aim of this study was to analyze the association between H. pylori infection and serum ferritin, a marker of the body iron stores. In this analysis, we paid particular attention to the role of dietary iron intake and CagA, an established virulence factor of the agent.METHODS:The analysis is based on a cross-sectional national health and nutrition survey among healthy people in Germany conducted in 1987/1988. The examination included a detailed questionnaire on medical history and lifestyle factors, a 7-day food record, and blood samples. Infection with H. pylori was measured serologically by ELISA and Westernblot.RESULTS:In total, 39.2% of 1806 persons aged 18 to 89 yr included in the study were H. pylori positive, of whom 57.6% had an infection with a CagA-positive H. pylori strain. Age- and sex-adjusted geometric mean of ferritin was 54.5 μg/dl among H. pylori-infected compared with 63.8 μg/dl among uninfected persons. A multiple linear regression model with log-transformed serum ferritin concentration as dependent variable and H. pylori infection and several potential confounding factors as independent variable was fitted. In this model, H. pylori infection was associated with a 17.0% decrease of the serum ferritin concentration (95% CI = 9.8–23.6). The association between H. pylori infection and serum ferritin levels did not vary by gender, age, and iron intake, and it was similar for CagA-positive and CagA-negative H. pylori infections.CONCLUSIONS:The decreased serum ferritin concentration among subjects infected with H. pylori might be induced by the uptake of ferritin in the stomach by H. pylori. Possible health implications of H. pylori-induced low ferritin levels warrant further investigation.

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.

Validation of self-reported cellular phone use

Background: In recent years, concern has been raised over possible adverse health effects of cellular telephone use. In epidemiological studies of cancer risk associated with the use of cellular telephones, the validity of self-reported cellular phone use has been problematic. Up to now there is very little information published on this subject. Methods:We conducted a study to validate the questionnaire used in an ongoing international case–control study on cellular phone use, the “Interphone study”. Self-reported cellular phone use from 68 of 104 participants who took part in our study was compared with information derived from the network providers over a period of 3 months (taken as the gold standard). Results:Using Spearmans rank correlation, the correlation between self-reported phone use and information from the network providers for cellular phone use in terms of the number of calls per day was good (r=0.62, 95% CI: 0.45–0.75), while that of the average duration of each call was rather moderate (r=0.34, 95% CI: 0.11–0.54). Similar results were found when Kappa coefficients were estimated. A value of r=0.56 (Spearmans correlation, CI: 0.38–0.70) was found for cumulative cellular phone use. Conclusion:Our study suggests that cellular phone use is easier to recall in terms of number of calls made than in terms of cumulative phone use and should thus be used as the basis for the dose–response analysis.

Assessment of radiofrequency exposure from cellular telephone daily use in an epidemiological study: German Validation study of the international case–control study of cancers of the brain—INTERPHONE-Study

Objective:The objective of the study is to validate self-reported cellular phone use information by comparing it with the cumulative emitted power and duration of calls measured by software-modified cellular phones (SMP). The information was obtained using a questionnaire developed for the international case–control study on the risk of the use of mobile phones in tumours of the brain or salivary gland (INTERPHONE-study). Method: The study was conducted in Bielefeld, Germany. Volunteers were asked to use SMPs instead of their own cellular phones for a period of 1 month. The SMP recorded the power emitted by the mobile phone handset during each base station contact. Information on cellular phone use for the same time period from traffic records of the network providers and from face-to-face interviews with the participants 3 months after the SMP use was assessed. Pearsons correlation coefficients and linear regression models were used to analyse the association between information from the interview and from the SMP. Results: In total, 1757 personal mobile phone calls were recorded for 45 persons by SMP and traffic records. The correlation between the self-reported information about the number and the duration of calls with the cumulative power of calls was 0.50 (P<0.01) and 0.48 (P<0.01), respectively. Almost 23% of the variance of the cumulative power was explained by either the number or the cumulative duration of calls. After inclusion of possible confounding factors in the regression model, the variance increased to 26%. Minor confounding factors were “network provider”, “contract form”, and “cellular phone model”. Discussion: The number of calls alone is a sufficient parameter to estimate the cumulative power emitted by the handset of a cellular telephone. The cumulative power emitted by these phones is only associated with number of calls but not with possible confounding factors. Using the mobile phone while driving, mainly in cities, or mainly in rural areas is not associated with the recorded cumulative power in the SMP.

Are Mobile Phones Harmful

There is increasing public interest in health risks of mobile phone use. Although there is a vast body of material on the biological effects of radiofrequency fields, current risk assessment is still limited. The article describes several hypotheses and results of biological effects such as thermal effect, genetic and carcinogenic effects and cancer related investigations. Mobile phones transmit and receive waves of frequencies mainly at 800?1800 MHz. Findings on the thermal effect of acute exposure to radiofrequency fields were consistent, resulting in an increase of cellular, tissue or body temperature by 1 °C or more. Guidelines for risk limits are based on this thermal effect. Experimental investigation suggests that radiofrequency fields are not tumor initiators and that if they are related to carcinogenicity, this would be by tumor promotion or by increasing the uptake of carcinogens in cells. Implications of these experimental results on public health concerns are yet unclear. Few epidemiological studies are available on the use of mobile phones or on the radiofrequency exposure and the development of cancer. Most of these studies have no or little quantitative exposure data and they are limited by the small number of observations. Large epidemiological studies are necessary in order to investigate the use of mobile phones on the development of cancer. It should be emphasized that even a small elevated risk may have a large implication for public health, as the use of mobile phones and the exposure is rapidly increasing.

Radiofrequency Electromagnetic Fields Emitted from Base Stations of DECT Cordless Phones and the Risk of Glioma and Meningioma (Interphone Study Group, Germany)

Abstract Schüz, J., Böhler, E., Schlehofer, B., Berg, G., Schlaefer, K., Hettinger, I., Kunna-Grass, K., Wahrendorf, J. and Blettner, M. Radiofrequency Electromagnetic Fields Emitted from Base Stations of DECT Cordless Phones and the Risk of Glioma and Meningioma (Interphone Study Group, Germany). Radiat. Res. 166, 116–119 (2006). The objective of this study was to test the hypothesis that exposure to continuous low-level radiofrequency electromagnetic fields (RF EMFs) increases the risk of glioma and meningioma. Participants in a population-based case-control study in Germany on the risk of brain tumors in relation to cellular phone use were 747 incident brain tumor cases between the ages of 30 and 69 years and 1494 matched controls. The exposure measure of this analysis was the location of a base station of a DECT (Digital Enhanced Cordless Telecommunications) cordless phone close to the bed, which was used as a proxy for continuous low-level exposure to RF EMFs during the night. Estimated odds ratios were 0.82 (95% confidence interval: 0.29–2.33) for glioma and 0.83 (0.29–2.36) for meningioma. There was also no increasing risk observed with duration of exposure to DECT cordless phone base stations. Although the study was limited due to the small number of exposed subjects, it is still a first indication that residential low-level exposure to RF EMFs may not pose a higher risk of brain tumors.