Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study.

The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of four regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case (CC) analysis and multiple imputation (MI) in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the UK. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with CC analysis or MI. We showed that RC methods resulted in more accurate estimation of the relation between mobile phone use and health outcomes, by combining self-reported data with objective operator-recorded data available for a subset of participants.

Mobile phone use and brain tumour risk - COSMOS, a prospective cohort study.

BACKGROUND: Each new generation of mobile phone technology has triggered discussions about potential carcinogenicity from exposure to radiofrequency electromagnetic fields (RF-EMF). Available evidence has been insufficient to conclude about long-term and heavy mobile phone use, limited by differential recall and selection bias, or crude exposure assessment. The Cohort Study on Mobile Phones and Health (COSMOS) was specifically designed to overcome these shortcomings. METHODS: We recruited participants in Denmark, Finland, the Netherlands, Sweden, and the UK 2007-2012. The baseline questionnaire assessed lifetime history of mobile phone use. Participants were followed through population-based cancer registers to identify glioma, meningioma, and acoustic neuroma cases during follow-up. Non-differential exposure misclassification was reduced by adjusting estimates of mobile phone call-time through regression calibration methods based on self-reported data and objective operator-recorded information at baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma, meningioma, and acoustic neuroma in relation to lifetime history of mobile phone use were estimated with Cox regression models with attained age as the underlying time-scale, adjusted for country, sex, educational level, and marital status. RESULTS: 264,574 participants accrued 1,836,479 person-years. During a median follow-up of 7.12 years, 149 glioma, 89 meningioma, and 29 incident cases of acoustic neuroma were diagnosed. The adjusted HR per 100 regression-calibrated cumulative hours of mobile phone call-time was 1.00 (95 % CI 0.98-1.02) for glioma, 1.01 (95 % CI 0.96-1.06) for meningioma, and 1.02 (95 % CI 0.99-1.06) for acoustic neuroma. For glioma, the HR for ≥ 1908 regression-calibrated cumulative hours (90th percentile cut-point) was 1.07 (95 % CI 0.62-1.86). Over 15 years of mobile phone use was not associated with an increased tumour risk; for glioma the HR was 0.97 (95 % CI 0.62-1.52). CONCLUSIONS: Our findings suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma.

Headache in the international cohort study of mobile phone use and health (COSMOS) in the Netherlands and the United Kingdom.

Headache is a common condition with a substantial burden of disease worldwide. Concerns have been raised over the potential impact of long-term mobile phone use on headache due to radiofrequency electromagnetic fields (RF-EMFs). We explored prospectively the association between mobile phone use at baseline (2009-2012) and headache at follow-up (2015-2018) by analysing pooled data consisting of the Dutch and UK cohorts of the Cohort Study of Mobile Phone Use and Health (COSMOS) (N = 78,437). Frequency of headache, migraine, and information on mobile phone use, including use of hands-free devices and frequency of texting, were self-reported. We collected objective operator data to obtain regression calibrated estimates of voice call duration. In the model mutually adjusted for call-time and text messaging, participants in the high category of call-time showed an adjusted odds ratio (OR) of 1.04 (95 % CI: 0.94-1.15), with no clear trend of reporting headache with increasing call-time. However, we found an increased risk of weekly headache (OR = 1.40, 95 % CI: 1.25-1.56) in the high category of text messaging, with a clear increase in reporting headache with increasing texting. Due to the negligible exposure to RF-EMFs from texting, our results suggest that mechanisms other than RF-EMFs are responsible for the increased risk of headache that we found among mobile phone users.

Risk factors for childhood brain tumours: A systematic review and meta-analysis of observational studies from 1976 to 2022.

BACKGROUND: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention. METHODS: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, during pregnancy and/or during post-natal period. Random effects meta-analysis was used to estimate summary effect sizes (ES) and 95% confidence intervals (CIs). We also quantified heterogeneity (I2) across studies. FINDINGS: A total of 4040 studies were identified, of which 181 studies (85 case-control and 96 cohort studies) met our criteria for inclusion. Of all eligible studies, 50% (n = 91) were conducted in Europe, 32% (n = 57) in North America, 9% (n = 16) in Australia, 8% (n = 15) in Asia, 1% (n = 2) in South America, and none in Africa. We found associations for some modifiable risk factors including childhood domestic exposures to insecticides (ES 1.44, 95% CI 1.20-1.73) and herbicides (ES 2.38, 95% CI 1.31-4.33). Maternal domestic exposure to insecticides (ES 1.45, 95% CI 1.09-1.94), maternal consumption of cured meat (ES 1.51, 95% CI 1.05-2.17) and coffee ≥ 2 cups/day (ES 1.45, 95% 95% CI 1.07-1.95) during pregnancy, and maternal exposure to benzene (ES 2.22; 95% CI 1.01-4.88) before conception were associated with CBTs in case-control studies. Also, paternal occupational exposure to pesticides (ES 1.48, 95% CI 1.23-1.77) and benzene (ES 1.74, 95% CI 1.10-2.76) before conception and during pregnancy were associated in case-control studies and in combined analysis. On the other hand, assisted reproductive technology (ART) (ES 1.32, 95% CI 1.05-1.67), caesarean section (CS) (ES 1.12, 95% CI 1.01-1.25), paternal occupational exposure to paint before conception (ES 1.56, 95% CI 1.02-2.40) and maternal smoking > 10 cigarettes per day during pregnancy (ES 1.18, 95% CI 1.00-1.40) were associated with CBT in cohort studies. Maternal intake of vitamins and folic acid during pregnancy was inversely associated in cohort studies. Hormonal/infertility treatment, breastfeeding, child day-care attendance, maternal exposure to electric heated waterbed, tea and alcohol consumption during pregnancy were among those not associated with CBT in both case-control and cohort studies. CONCLUSION: Our results should be interpreted with caution, especially as most associations between risk factors and CBT were discordant between cohort and case-control studies. At present, it is premature for any CBT to define specific primary prevention guidelines.

Time trends in mobile phone use and glioma incidence among males in the Nordic Countries, 1979-2016.

INTRODUCTION: In the Nordic countries, the use of mobile phones increased sharply in the mid-1990s especially among middle-aged men. We investigated time trends in glioma incidence rates (IR) with the perspective to inform about the plausibility of brain tumour risks from mobile phone use reported in some case-control studies. METHODS: We analysed IR of glioma in Denmark, Finland, Norway, and Sweden among men aged 40-69 years, using data from national cancer registries and population statistics during 1979-2016, using log-linear joinpoint analysis. Information on regular mobile phone use and amount of call-time was obtained from major studies of mobile phones in these countries. We compared annual observed incidence with that expected under various risk scenarios to assess which of the reported effect sizes are compatible with the observed IR. The expected numbers of cases were computed accounting for an impact of other factors besides mobile phone use, such as improved cancer registration. RESULTS: Based on 18,232 glioma cases, IR increased slightly but steadily with a change of 0.1% (95 %CI 0.0%; 0.3%) per year during 1979-2016 among 40-59-year-old men and for ages 60-69, by 0.6 % (95 %CI 0.4; 0.9) annually. The observed IR trends among men aged 40-59 years were incompatible with risk ratios (RR) 1.08 or higher with a 10-year lag, RR ≥ 1.2 with 15-year lag and RR ≥ 1.5 with 20-year lag. For the age group 60-69 years, corresponding effect sizes RR ≥ 1.4, ≥2 and ≥ 2.5 could be rejected for lag times 10, 15 and 20 years. DISCUSSION: This study confirms and reinforces the conclusions that no changes in glioma incidence in the Nordic countries have occurred that are consistent with a substantial risk attributable to mobile phone use. This particularly applies to virtually all reported risk increases reported by previous case-control studies with positive findings.

Association of allergic diseases and epilepsy with risk of glioma, meningioma and acoustic neuroma: results from the INTERPHONE international case-control study.

We investigated the association of allergic diseases and epilepsy with risk of brain tumours, in Interphone, a 13-country case-control study. Data were obtained from 2693 glioma cases, 2396 meningioma cases, and 1102 acoustic neuroma cases and their 6321 controls. Conditional logistic regression models were used to estimate pooled odds ratios (ORs) and their respective 95% confidence intervals (CIs), adjusted for education and time at interview. Reduced ORs were observed for glioma in relation to physician-diagnosed asthma (OR = 0.73; CI 0.58-0.92), hay fever (OR 0.72; CI 0.61-0.86), and eczema (OR 0.78, CI 0.64-0.94), but not for meningioma or acoustic neuroma. Previous diagnosis of epilepsy was associated with an increased OR for glioma (2.94; CI 1.87-4.63) and for meningioma (2.12; CI 1.27-3.56), but not for acoustic neuroma. This large-scale case-control study adds to the growing evidence that people with allergies have a lower risk of developing glioma, but not meningioma or acoustic neuroma. It also supports clinical observations of epilepsy prior to the diagnosis of glioma and meningioma.

Exposure To Extremely Low-Frequency Magnetic Fields In Low- And Middle-Income Countries: An Overview.

To compare extremely low-frequency magnetic field (ELF-MF) exposure in the general population in low- and middle-income countries (LMICs) with high-income countries (HIC), we carried out a systematic literature search resulting in 1483 potentially eligible articles; however, only 25 studies could be included in the qualitative synthesis. Studies showed large heterogeneity in design, exposure environment and exposure assessment. Exposure assessed by outdoor spot measurements ranged from 0.03 to 4µT. Average exposure by indoor spot measurements in homes ranged from 0.02 to 0.4µT. Proportions of homes exposed to a threshold of ≥0.3µT were many times higher in LMICs compared to HIC. Based on the limited data available, exposure to ELF-MF in LMICs appeared higher than in HIC, but a direct comparison is hampered by a lack of representative and systematic monitoring studies. Representative measurement studies on residential exposure to ELF-MF are needed in LMICs together with better standardisation in the reporting.

Long-term effect of mobile phone use on sleep quality: Results from the cohort study of mobile phone use and health (COSMOS).

BACKGROUND: Effects of radiofrequency electromagnetic field exposure (RF-EMF) from mobile phone use on sleep quality has mainly been investigated in cross-sectional studies. The few previous prospective cohort studies found no or inconsistent associations, but had limited statistical power and short follow-up. In this large prospective cohort study, our aim was to estimate the effect of RF-EMF from mobile phone use on different sleep outcomes. MATERIALS AND METHODS: The study included Swedish (n = 21,049) and Finnish (n = 3120) participants enrolled in the Cohort Study of Mobile Phone Use and Health (COSMOS) with information about operator-recorded mobile phone use at baseline and sleep outcomes both at baseline and at the 4-year follow-up. Sleep disturbance, sleep adequacy, daytime somnolence, sleep latency, and insomnia were assessed using the Medical Outcome Study (MOS) sleep questionnaire. RESULTS: Operator-recorded mobile phone use at baseline was not associated with most of the sleep outcomes. For insomnia, an odds ratio (OR) of 1.24, 95% CI 1.03-1.51 was observed in the highest decile of mobile phone call-time (>258 min/week). With weights assigned to call-time to account for the lower RF-EMF exposure from Universal Mobile Telecommunications Service (UMTS, 3G) than from Global System for Mobile Communications (GSM, 2G) the OR was 1.09 (95% CI 0.89-1.33) in the highest call-time decile. CONCLUSION: Insomnia was slightly more common among mobile phone users in the highest call-time category, but adjustment for the considerably lower RF-EMF exposure from the UMTS than the GSM network suggests that this association is likely due to other factors associated with mobile phone use than RF-EMF. No association was observed for other sleep outcomes. In conclusion, findings from this study do not support the hypothesis that RF-EMF from mobile phone use has long-term effects on sleep quality.

Smokeless Tobacco Use, Cigarette Smoking, and Upper Aerodigestive Tract Cancers: A Case-Control Study in the Batna Region, Algeria, 2008-2011.

BACKGROUND: A significant proportion of the Algerian population uses tobacco products and is at risk of developing tobacco-associated cancers. AIMS: This case-control study reports on the association between tobacco use and the occurrence of upper aerodigestive tract (UADT) cancers in Batna, Algeria. METHODS: Incident primary UADT cancer cases in residents of Batna in 2008-2011 were identified using the regional tumor registry. One hospital and 1 population control were matched to each case by sex, year of birth, and residence. Information on tobacco use was collected, and odds ratios (ORs) were obtained using conditional logistic regression also after sex stratification. RESULTS: The study included 192 cases (80%) of the 241 primary UADT cancer cases identified and 384 controls. Males represented 76.6% of cancer cases. Cancers of the nasopharynx (48%) and the larynx (26%) were the most common types. Ever use of smokeless tobacco (ST) (OR = 1.0; 95% confidence interval [CI]: 0.6-1.5) or current ST use (OR = 1.1; 95% CI: 0.6-1.7) was not associated with overall risk of UADT cancers. Associations with cancers of the nasopharynx (OR = 1.5; 95% CI: 0.5-4.6) and oral cavity/oropharynx (OR = 3.0; 95% CI: 0.8-11.8) were found when comparing use of ST only to no consumption of any tobacco. Cigarette smoking was associated with an increase in the overall risk of UADT cancers, with a 3-fold increase in the risk of laryngeal cancer when comparing smoking only to no consumption of any tobacco (OR = 3.3; 95% CI: 1.0-11.5). Associations for smokers who also consumed ST differed by cancer site. CONCLUSION: In this study from Algeria dominated by male cases and by cancer in the nasopharynx, cigarette smoking but not ST was associated with UADT cancer. Analyses by anatomical site and using as reference never use of any type of tobacco suggested few associations with ST but of lower precision.

A genome-wide association study on medulloblastoma.

INTRODUCTION: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. METHODS: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. RESULTS: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10-5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10-8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10-4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10-3). CONCLUSION: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

Genetic Variants in the 9p21.3 Locus Associated with Glioma Risk in Children, Adolescents, and Young Adults: A Case-Control Study.

BACKGROUND: Genome-wide association studies have identified germline genetic variants in 25 genetic loci that increase the risk of developing glioma in adulthood. It is not known if these variants increase the risk of developing glioma in children and adolescents and young adults (AYA). To date, no studies have performed genome-wide analyses to find novel genetic variants associated with glioma risk in children and AYA. METHODS: We investigated the association between 8,831,628 genetic variants and risk of glioma in 854 patients diagnosed up to the age of 29 years and 3,689 controls from Sweden and Denmark. Recruitment of patients and controls was population based. Genotyping was performed using Illumina BeadChips, and untyped variants were imputed with IMPUTE2. We selected 41 established adult glioma risk variants for detailed investigation. RESULTS: Three adult glioma risk variants, rs634537, rs2157719, and rs145929329, all mapping to the 9p21.3 (CDKN2B-AS1) locus, were associated with glioma risk in children and AYA. The strongest association was seen for rs634537 (odds ratioG = 1.21; 95% confidence interval = 1.09-1.35; P = 5.8 × 10-4). In genome-wide analysis, an association with risk was suggested for 129 genetic variants (P <1 × 10-5). CONCLUSIONS: Carriers of risk alleles in the 9p21.3 locus have an increased risk of glioma throughout life. The results from genome-wide association analyses require validation in independent cohorts. IMPACT: Our findings line up with existing evidence that some, although not all, established adult glioma risk variants are associated with risk of glioma in children and AYA. Validation of results from genome-wide analyses may reveal novel susceptibility loci for glioma in children and AYA.

Validation of self-reported occupational noise exposure in participants of a French case-control study on acoustic neuroma.

OBJECTIVES: To validate self-reported occupational loud noise exposure against expert evaluation of noise levels in a French case-control study on acoustic neuroma and to estimate the impact of exposure misclassification on risk estimation. METHODS: Noise levels were evaluated in 1006 jobs held by 111 cases and 217 population controls by an expert. Case-control differences in self-reporting were analyzed with logistic models. Sensitivity, specificity, positive and negative predictive values, and observed agreement of the self-reports were computed relative to the expert evaluation. They were used to calibrate the odds ratio (OR) between lifetime ever occupational loud noise exposure and the risk of acoustic neuroma, without adjustment for measurement error of the expert assessments. RESULTS: Cases reported noise levels in individual jobs closer to the expert assessment than controls, but the case-control difference was small for lifetime exposures. For expert-rated exposure of 80 dB(A), reporting of individual jobs by cases was more sensitive (54% in cases, 37% in controls), whereas specificity (91% in cases, 93% in controls) and observed agreement (82% in cases, 81% in controls) were similar. When lifetime exposure was considered, sensitivity increased (76% in cases, 65% in controls), while cases specificity decreased (84%). When these values were used to calibrate self-reports for exposure misclassification compared to expert evaluation at 80 dB(A), the crude OR of 1.7 was reduced to 1.3. CONCLUSIONS: Despite the relatively accurate reporting of loud noise, the impact of the calibration on the OR was non-negligible.

Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case‒control study.

Objective Studies of loud noise exposure and vestibular schwannomas (VS) have shown conflicting results. The population-based INTERPHONE case‒control study was conducted in 13 countries during 2000-2004. In this paper, we report the results of analyses on the association between VS and self-reported loud noise exposure. Methods Self-reported noise exposure was analyzed in 1024 VS cases and 1984 matched controls. Life-long noise exposure was estimated through detailed questions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using adjusted conditional logistic regression for matched sets. Results The OR for total work and leisure noise exposure was 1.6 (95% CI 1.4-1.9). OR were 1.5 (95% CI 1.3-1.9) for only occupational noise, 1.9 (95% CI 1.4-2.6) for only leisure noise and 1.7 (95% CI 1.2-2.2) for exposure in both contexts. OR increased slightly with increasing lag-time. For occupational exposures, duration, time since exposure start and a metric combining lifetime duration and weekly exposure showed significant trends of increasing risk with increasing exposure. OR did not differ markedly by source or other characteristics of noise. Conclusion The consistent associations seen are likely to reflect either recall bias or a causal association, or potentially indicate a mixture of both.

Survival of glioma patients in relation to mobile phone use in Denmark, Finland and Sweden.

PURPOSE: Gliomas are the most common cancer of the brain, with a poor prognosis in particular for glioblastoma. In 2014, a study suggested reduced survival in relation to latency of mobile phone use among glioblastoma patients. A joint epidemiological/experimental project to study effects of RF-EMF on tumor development and progression was established. The current analysis relates to the epidemiological part and addresses whether pre-diagnostic mobile phone use was associated with survival among glioma patients. METHODS: Glioma cases (n = 806) previously enrolled in a collaborative population-based case-control study in Denmark, Finland and Sweden were followed up for survival. Vital status, date of death, date of emigration, or date last known to be alive was obtained based on registry linkages with a unique personal ID in each country. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) stratified by country. Covariates investigated were sex, age, education, histology, treatment, anatomic location and marital status. RESULTS: No indication of reduced survival among glioblastoma patients was observed for various measures of mobile phone use (ever regular use, time since start of regular use, cumulative call time overall or in the last 12 months) relative to no or non-regular use. All significant associations suggested better survival for mobile phone users. Results were similar for high-grade and low-grade gliomas. CONCLUSIONS: We found no evidence of reduced survival among glioma patients in relation to previous mobile phone use.

Possible effects of radiofrequency electromagnetic fields on in vivo C6 brain tumors in Wistar rats.

PURPOSE: Glioblastoma is a malignant brain tumor which has one of the poorest prognosis. It is not clear if toxic environmental factors can influence its aggressiveness. Recently, it was suggested that brain cancer patients with heavy cell phone use showed reduced survival. Here we aimed to assess the effect of controlled brain averaged specific absorption rate (BASAR) from heavy use of cell phone radiofrequency electromagnetic fields (RF-EMF) on in vivo C6 brain tumors in Wistar rats. METHODS: C6 cells grafted male rats were exposed to GSM 900 MHz signal at environmental BASAR, 0 (sham), 0.25 or 0.5 W/kg (5 days a week, 45 min a day in restraint), or were cage controls (no restraint). At death, tumor volume and immunohistochemistry for CD31, cleaved caspase (CC) 3 and Ki67 were assessed to examine vascularization, apoptosis and cellular divisions, respectively. Moreover, immune cell invasion, necrosis and mitotic index were determined. RESULTS: Results showed no BASAR effect on survival (31 days post-graft median), tumor volume, mitotic index, vascularization, infiltration, necrosis or cell division. However, results suggested a BASAR-dependent reduction of immune cell invasion and apoptosis. CONCLUSIONS: Our data suggested an action of RF-EMF by reducing immune cell invasion and glioblastoma cell apoptosis, at probably too low amplitude to impact survival. Further replication studies are needed to confirm these observations.

An international prospective cohort study of mobile phone users and health (COSMOS): Factors affecting validity of self-reported mobile phone use.

This study investigates validity of self-reported mobile phone use in a subset of 75 993 adults from the COSMOS cohort study. Agreement between self-reported and operator-derived mobile call frequency and duration for a 3-month period was assessed using Cohen's weighted Kappa (κ). Sensitivity and specificity of both self-reported high (≥10 calls/day or ≥4h/week) and low (≤6 calls/week or <30min/week) mobile phone use were calculated, as compared to operator data. For users of one mobile phone, agreement was fair for call frequency (κ=0.35, 95% CI: 0.35, 0.36) and moderate for call duration (κ=0.50, 95% CI: 0.49, 0.50). Self-reported low call frequency and duration demonstrated high sensitivity (87% and 76% respectively), but for high call frequency and duration sensitivity was lower (38% and 56% respectively), reflecting a tendency for greater underestimation than overestimation. Validity of self-reported mobile phone use was lower in women, younger age groups and those reporting symptoms during/shortly after using a mobile phone. This study highlights the ongoing value of using self-report data to measure mobile phone use. Furthermore, compared to continuous scale estimates used by previous studies, categorical response options used in COSMOS appear to improve validity considerably, most likely by preventing unrealistically high estimates from being reported.

Cancers of the brain and CNS: global patterns and trends in incidence.

Background: Cancers of the brain and CNS constitute a group of rare and heterogeneous tumors. Increasing incidence in Western populations has been linked to improvements in diagnostic technology, although interpretation is hampered by changes in diagnosis and reporting. The present study examines geographic and temporal variations in incidence rates of brain and CNS cancers worldwide. Methods: Data from successive volumes of Cancer Incidence in Five Continents were used, including 96 registries in 39 countries. We used Joinpoint regression to estimate the average annual percentage change and its 95% CI. Results: Globally, a large variability in the magnitude of the diagnosis of new cases of brain and CNS cancer was found, with a 5-fold difference between the highest rates (mainly in Europe) and the lowest (mainly in Asia). Increasing rates of brain and CNS cancer were found in South America, namely in Ecuador, Brazil, and Colombia; in eastern Europe (Czech Republic and Russia), in southern Europe (Slovenia), and in the 3 Baltic countries. Trends were similar between sexes, although decreasing trends in men and women were seen in Japan and New Zealand. Conclusions: Important regional variations in brain and CNS cancers exist, and given an increasing burden and risk worldwide, there is a need for further etiological research that focuses on the elucidation of environmental risk. The trends are sufficiently complex and diffuse, however, to warrant a cautious approach to interpretation.