Brigitte Schlehofer

Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium.

Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the groups consensus on the current state of scientific findings, and they present a consensus on research priorities to identify which important areas the science should move to address. Cancer 2008;113(7 suppl):1953–68.

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.

Role of medical history in brain tumour development. Results from the international adult brain tumour study

In an international population‐based case‐control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age‐ and gender‐matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR = 6.55, 95% CI 3.40–12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti‐epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR = 0.59, 95% CI 0.49–0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR = 0.72, 95% CI 0.61–0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation. Int. J. Cancer82:155–160, 1999.

Medical risk factors and the development of brain tumors

Several diseases and medical treatments are discussed as risk factors for the development of brain tumors. A population‐based case‐control study in the Rhein‐Neckar‐Odenwald area (containing 1.3 million inhabitants) of Germany was established to investigate this question. A total of 226 patients (cases) with primary brain tumors (International Classification of Diseases, ninth edition, classes 191, 191.1, and 192.0) and 418 control subjects (controls) were interviewed using a standardized questionnaire over a period of 2 years. No association was seen for head injuries, hereditary diseases, family history, and radiographic examination of the head and teeth. However, more cases than controls had had meningitis (relative risk [RR], 2.7; 95% confidence interval [CI], 0.9 to 8.6) or epilepsy (RR, 2.6; 95% CI, 0.6 to 11.7). The RR was decreased for those who had allergic diseases (RR, 0.7; 95% CI, 0.5 to 1.0), diabetes (RR, 0.7; 95% CI, 0.3 to 1.8), and infections and colds (RR, 0.3; 95% CI, 0.1 to 0.8).

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.

International renal-cell-cancer study. VI. The role of medical and family history

A number of medical conditions have been linked with renal‐cell cancer, although the evidence is not consistent in every case. In a large international case‐control study of renal‐cell cancer, we examined, among other hypotheses, associations with a personal history of certain medical conditions and a family history of cancer of the kidney or thyroid. Relative risks (RR), adjusted for the effects of age, gender, body‐mass index, tobacco smoking and study centre, were significantly increased by a history of kidney stones or thyroid or kidney disease. The RR were not altered by additional adjustment for hypertension, or when diagnoses were restricted to those made at least 5 or 10 years before 1987 (the usual “cut‐off” date). The link with kidney injury is particularly likely to be affected by recall bias. Increased RR of borderline significance were found for kidney infection (RR, 1.2) and diabetes (RR, 1.4). Having one first‐degree relative with kidney cancer was associated with a significantly increased risk of renal‐cell cancer (RR, 1.6; 95% Cl, 1.1–2.4). Seven cases reported 2 first‐degree relatives with kidney cancer. No controls had first‐degree relatives with kidney cancer. None of our participants reported having von Hippel‐Lindau disease. The data suggests that a few conditions of the kidney are strongly associated with renal‐cell cancer and that heredity plays a role in a small proportion of cases.

Mobile phone base stations and adverse health effects: phase 1 of a population-based, cross-sectional study in Germany

Objective: The aim of this first phase of a cross-sectional study from Germany was to investigate whether proximity of residence to mobile phone base stations as well as risk perception is associated with health complaints. Methods: The researchers conducted a population-based, multi-phase, cross-sectional study within the context of a large panel survey regularly carried out by a private research institute in Germany. In the initial phase, reported on in this paper, 30 047 persons from a total of 51 444 who took part in the nationwide survey also answered questions on how mobile phone base stations affected their health. A list of 38 health complaints was used. A multiple linear regression model was used to identify predictors of health complaints including proximity of residence to mobile phone base stations and risk perception. Results: Of the 30 047 participants (response rate 58.6%), 18.7% of participants were concerned about adverse health effects of mobile phone base stations, while an additional 10.3% attributed their personal adverse health effects to the exposure from them. Participants who were concerned about or attributed adverse health effects to mobile phone base stations and those living in the vicinity of a mobile phone base station (500 m) reported slightly more health complaints than others. Conclusions: A substantial proportion of the German population is concerned about adverse health effects caused by exposure from mobile phone base stations. The observed slightly higher prevalence of health complaints near base stations can not however be fully explained by attributions or concerns.

Mobile phone base stations and adverse health effects: phase 2 of a cross-sectional study with measured radio frequency electromagnetic fields

Objective: The aim of the cross-sectional study was to test the hypothesis that exposure to continuous low-level radio frequency electromagnetic fields (RF-EMFs) emitted from mobile phone base stations was related to various health disturbances. Methods: For the investigation people living mainly in urban regions were selected from a nationwide study in 2006. In total, 3526 persons responded to a questionnaire (response rate 85%). For the exposure assessment a dosimeter measuring different RF-EMF frequencies was used. Participants answered a postal questionnaire on how mobile phone base stations affected their health and they gave information on sleep disturbances, headaches, health complaints and mental and physical health using standardised health questionnaires. Information on stress was also collected. Multiple linear regression models were used with health outcomes as dependent variables (n = 1326). Results: For the five health scores used, no differences in their medians were observed for exposed versus non-exposed participants. People who attributed adverse health effects to mobile phone base stations reported significantly more sleep disturbances and health complaints, but they did not report more headaches or less mental and physical health. Individuals concerned about mobile phone base stations did not have different well-being scores compared with those who were not concerned. Conclusions: In this large population-based study, measured RF-EMFs emitted from mobile phone base stations were not associated with adverse health effects.

Lack of association of herpesviruses with brain tumors

Gliomas are the most frequent primary brain tumors in humans. Many studies have been carried out on their etiology; however, the only confirmed risk factors are hereditary predisposing conditions and high dose of ionizing radiation. Recently, human cytomegalovirus (HCMV) gene products and nucleic acids were reported to be present in all of 27 glioma samples investigated in contrast to other brain tissues, and it was hypothesized that HCMV might play a role in glioma pathogenesis. To evaluate these findings, samples of 40 gliomas, 31 meningiomas, and 6 acoustic neurinomas (ACNs) were analyzed for the presence of HCMV macromolecules using polymerase chain reaction (PCR) and immunohistochemistry. Additionally, corresponding blood samples from 72 patients were analyzed for the presence of HCMV DNA to check for a possible contamination of tumor tissues with HCMV-infected blood cells. No HCMV DNA sequences were found, neither in brain tumor tissues nor in corresponding blood samples. Immunohistochemistry did not detect HCMV-specific proteins. Addressing a possible role of other herpesviruses as has been suggested in seroepidemiological studies, seroprevalences of antibodies to HCMV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), and varicella-zoster virus (VZV) were determined by enzyme-linked immunosorbent assay (ELISA). Serological analyses of brain tumor patients showed no significant differences in the prevalences of antibodies to HCMV, HSV, EBV, or VZV compared to the general population. Thus, the data of the present study do not support the hypothesis of an association of herpesviruses with the development of primary brain tumors.

Reproductive factors and exogenous hormone use in relation to risk of glioma and meningioma in a large European cohort study

Background: The etiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and the risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma cases were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (95% CI). Results: No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR, 3.61; 95% CI, 1.75-7.46). Conclusion: Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, seems to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation. Impact: Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements. Cancer Epidemiol Biomarkers Prev; 19(10); 2562–9. ©2010 AACR.