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.

Clinical presentation of young people (10-24 years old) with brain tumors: results from the international MOBI-Kids study.

INTRODUCTION: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). METHODS: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location. RESULTS: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays. CONCLUSIONS: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis.

Simulation of the incidence of malignant brain tumors in birth cohorts that started using mobile phones when they first became popular in Japan.

Over 20 years have passed since the initial spread of mobile phones in Japan. Epidemiological studies of mobile phone use are currently being conducted around the world, but scientific evidence is inconclusive. The present study aimed to simulate the incidence of malignant brain tumors in cohorts that began using mobile phones when they first became popular in Japan. Mobile phone ownership data were collected through an Internet-based questionnaire survey of subjects born between 1960 and 1989. The proportion of mobile phone ownership between 1990 and 2012 was calculated by birth cohort (1960s, 1970s, and 1980s). Subsequently, using the ownership proportion, the incidence of malignant brain tumors was calculated under simulated risk conditions. When the relative risk was set to 1.4 for 1,640 h or more of cumulative mobile phone use and the mean daily call duration was 15 min, the incidence of malignant brain tumors in 2020 was 5.48 per 100,000 population for the 1960s birth cohort, 3.16 for the 1970s birth cohort, and 2.29 for the 1980s birth cohort. Under the modeled scenarios, an increase in the incidence of malignant brain tumors was shown to be observed around 2020. © 2019 Bioelectromagnetics Society.

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.

Nonparticipation Selection Bias in the MOBI-Kids Study.

BACKGROUND: MOBI-Kids is a 14-country case-control study designed to investigate the potential effects of electromagnetic field exposure from mobile telecommunications devices on brain tumor risk in children and young adults conducted from 2010 to 2016. This work describes differences in cellular telephone use and personal characteristics among interviewed participants and refusers responding to a brief nonrespondent questionnaire. It also assesses the potential impact of nonparticipation selection bias on study findings. METHODS: We compared nonrespondent questionnaires completed by 77 cases and 498 control refusers with responses from 683 interviewed cases and 1501 controls (suspected appendicitis patients) in six countries (France, Germany, Israel, Italy, Japan, and Spain). We derived selection bias factors and estimated inverse probability of selection weights for use in analysis of MOBI-Kids data. RESULTS: The prevalence of ever-regular use was somewhat higher among interviewed participants than nonrespondent questionnaire respondents 10-14 years of age (68% vs. 62% controls, 63% vs. 48% cases); in those 20-24 years, the prevalence was ≥97%. Interviewed controls and cases in the 15- to 19- and 20- to 24-year-old age groups were more likely to have a time since start of use of 5+ years. Selection bias factors generally indicated a small underestimation in cellular telephone odds ratios (ORs) ranging from 0.96 to 0.97 for ever-regular use and 0.92 to 0.94 for time since start of use (5+ years), but varied in alternative hypothetical scenarios considered. CONCLUSIONS: Although limited by small numbers of nonrespondent questionnaire respondents, findings generally indicated a small underestimation in cellular telephone ORs due to selective nonparticipation.

Analysis of ear side of mobile phone use in the general population of Japan.

This study aimed to clarify the distribution of the ear side of mobile phone use in the general population of Japan and clarify what factors are associated with the ear side of mobile phone use. Children at elementary and junior high schools (n = 2,518) and adults aged ≥20 years (n = 1,529) completed an Internet-based survey. Data were subjected to a logistic regression analysis. In children, due to the tendency to use the dominant hand, we analyzed the factors associated with the use of right ear in right-handed people. Statistically significant differences were observed only in talk time per call (odds ratio (OR) = 2.17; 95% confidence interval (CI): 1.22-3.99). In adults, due to the tendency to use the left ear, we analyzed factors associated with the use of left ear in right-handed people. Significant differences were observed in those aged 30-39 years (OR = 2.55; 95% CI: 1.79-3.68), those aged 40-49 years (OR = 3.08; 95% CI: 2.15-4.43), those aged >50 years (OR = 1.85; 95% CI: 1.20-2.85), and in those with a percentage of total talk time when using mobile phones at work of 51-100% (OR = 1.75; 95% CI: 1.21-2.55). We believe that future epidemiological studies on mobile phone use can be improved by considering the trends in mobile phone use identified in this study. Bioelectromagnetics. 39:53-59, 2018. © 2017 Wiley Periodicals, Inc.

Work Sustainability Among Male Cancer Survivors After Returning to Work.

BACKGROUND: Few studies have investigated the work continuance rate among cancer survivors after return to work (RTW). The objective of this study was to clarify work sustainability after RTW among Japanese male cancer survivors. METHODS: We collected data on male cancer survivors from an occupational health register. Inclusion criteria were as follows: employees who returned to work after an episode of sick leave due to clinically certified cancer diagnosed between January 1, 2000 and December 31, 2011. RESULTS: Of 1,033 male employees who were diagnosed with cancer, 786 employees (76.1%) returned to work after their first episode of sick leave due to cancer. Work continuance rates among all subjects were 80.1% 1 year after RTW and 48.5% 5 years after RTW. The mean duration of work after RTW was 4.5 years. The work continuance rates varied significantly by cancer type. The "Lung" and "Hepatic, Pancreatic" cancer groups had the shortest duration of work (0.9 year after RTW). CONCLUSIONS: Of workers who returned to work after their first episode of leave after cancer, 50% continued to work after 5 years in large-scale companies. There was a steep decrease in work continuance rates during the first year after RTW, with considerable differences according to cancer site.

Analysis of mobile phone use among young patients with brain tumors in Japan.

The purpose of this study was to clarify ownership and usage of mobile phones among young patients with brain tumors in Japan. The subjects of this study were patients with brain tumors diagnosed between 2006 and 2010 who were between the ages of 6 and 18 years. The target population for the analysis was 82 patients. Patients were divided into two groups: 16 patients who were mobile phone owners 1 year before diagnosis, and 66 patients who did not own mobile phones (non-owners). Using data on the mobile phone ownership rate obtained from three general-population surveys, we calculated the expected number of mobile phone owners. The three age-adjusted standardized ownership ratios were 0.83 (95% confidence interval [CI]: 0.56-1.22), 0.51 (95% CI: 0.24-1.04), and 0.75 (95% CI: 0.42-1.32). The mobile phone ownership prevalence among the young Japanese patients with brain tumors in the current study does not differ from available estimates for the general population of corresponding age. However, since the use of mobile phones among children is increasing annually, investigations into the health effects of mobile phone use among children should continue. Bioelectromagnetics. 38:349-355, 2017. © 2017 Wiley Periodicals, Inc.

The Intracranial Distribution of Gliomas in Relation to Exposure From Mobile Phones: Analyses From the INTERPHONE Study.

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self-reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially influenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use.

Time trend in incidence of malignant neoplasms of the central nervous system in relation to mobile phone use among young people in Japan.

The aim of this study was to examine whether incidence of malignant neoplasms of the central nervous system from 1993 to 2010 has increased among young people in Japan, and whether the increase could be explained by increase in mobile phone use. Joinpoint regression analysis of incidence data was performed. Subsequently, the expected incidence rate was calculated assuming that the relative risk was 1.4 for those who used mobile phones more than 1640 h cumulatively. Annual percent change was 3.9% (95% confidence interval [CI], 1.6-6.3) for men in their 20s from 1993 to 2010, 12.3% (95% CI, 3.3-22.1) for women in their 20s from 2002 to 2010, 2.7% (95% CI, 1.3-4.1) for men in their 30s from 1993 to 2010, and 3.0% (95% CI, 1.4-4.7) for women in their 30s from 1993 to 2010. Change in incidence rates from 1993 to 2010 was 0.92 per 100,000 people for men in their 20s, 0.83 for women in their 20s, 0.89 for men in their 30s, and 0.74 for women in their 30s. Change in expected incidence rates from 1993 to 2010 was 0.08 per 100,000 people for men in their 20s, 0.03 for women in their 20s, 0.15 for men in their 30s, and 0.05 for women in their 30s. Patterns in sex-, age-, and period-specific incidence increases are inconsistent with sex-, age-, and period-specific prevalence trends, suggesting the overall incidence increase cannot be explained by heavy mobile phone use. Bioelectromagnetics. 37:282-289, 2016. © 2016 Wiley Periodicals, Inc.

Returning to work after sick leave due to cancer: a 365-day cohort study of Japanese cancer survivors.

PURPOSE: More employees are experiencing a cancer diagnosis during their working-age years, yet there have been no large-scale Japanese studies investigating sick leave due to cancer. We clarified differences in the cumulative partial and full return to work (RTW) rates between different cancer types among Japanese cancer survivors. METHODS: Data on Japanese employees who experienced an episode of sick leave due to clinically certified cancer diagnosed between 1 January 2000 and 31 December 2011 were obtained from an occupational health register. Subject outcomes within the 365-day period following their initial day of sick leave were utilized for this study. We investigated the cumulative partial/full and full RTW rates by using survival analysis with competing risks and predictors of time to RTW by a Fine-Gray proportional hazard regression model. RESULTS: One thousand two hundred seventy-eight subjects (1033 males and 245 females) experienced their first episode of sick leave due to cancer during the 12-year follow-up period. Of the subjects, 47.1% returned to work full time within 6 months of their initial day of sick leave absence, and 62.3% by 12 months. The cumulative RTW rate varied significantly by cancer type. There were considerable differences in the range of cumulative full RTW rates between the two categories ("lower full RTW rate" groups ("lung," "hepatic, pancreatic," "esophageal," and "blood" cancer groups) vs. "higher full RTW rate" groups ("gastric," "intestinal," "breast," "female genital," "male genital," "urinary"): 6.3 to 14.3% vs. 11.4 to 28.3% at 60 days, 10.6 to 22.4% vs. 27.0 to 50.0% at 120 days, 21.3 to 34.7% vs. 38.5 to 65.4% at 180 days, 34.3 to 42.9% vs. 66.0 to 79.5% at 365 days). Additionally, older age may be associated with a longer time to full RTW. CONCLUSIONS: More than half of the subjects returned to work full-time within the 365-day period following their initial day of sick leave, with cumulative RTW rates varying by cancer type. Older employees may require a longer time to full RTW. IMPLICATIONS OF CANCER SURVIVORS: It is very important for companies (especially small- and medium-sized companies) to establish and improve their RTW support system for cancer survivors, with knowledge that the median time to RTW is expected to be at least a few months.

The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk.

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people.

Lifestyle factors as predictors of general cardiovascular disease: use for early self-screening.

This study aims to examine the effectiveness of lifestyle factors in predicting general cardiovascular events and to investigate the feasibility of using the lifestyle model as a self-screening tool. The authors conducted a longitudinal study over a 10-year follow-up in Japan. Logistic regression analysis was used to create prediction models for general cardiovascular disease (CVD) death. The authors estimated the predictive power of the models by calculating the area under the receiver operating characteristic (AUROC) curve. The total of 6 traditional and 5 lifestyle risk factors were significantly associated with the incidence of CVD events. Hazard ratios (HRs) were 0.26 (95% confidence interval [CI] = 0.17, 0.41) for regular physical activity, 0.57 (95% CI = 0.50, 0.67) for moderate- or high-intensity work, and 1.72 (95% CI = 1.31-2.26) for short sleep duration; the HRs for traditional and Western dietary patterns were 1.53 (95% CI = 1.12, 2.09) and 2.62 (95% CI = 1.46, 4.68), respectively. The AUROC curve was significantly different between the classic and lifestyle prediction models. These results suggest that lifestyle factors are significant predictors of CVD events.

[The IARC carcinogenicity evaluation of radio-frequency electromagnetic field: with special reference to epidemiology of mobile phone use and brain tumor risk].

The International Agency for Research on Cancer of World Health Organization announced in May 2011 the results of evaluation of carcinogenicity of radio-frequency electromagnetic field. In the overall evaluation, the radio-frequency electromagnetic field was classified as "possibly carcinogenic to humans", on the basis of the fact that the evidence provided by epidemiological studies and animal bioassays was limited. Regarding epidemiology, the results of the Interphone Study, an international collaborative case-control study, were of special importance, together with the results of a prospective cohort study in Denmark, case-control studies in several countries, and a case-case study in Japan. The evidence obtained was considered limited, because the increased risk observed in some studies was possibly spurious, caused by selection bias or recall bias as well as residual effects of confounding factors. Further research studies, such as large-scale multinational epidemiological studies, are crucially needed to establish a sound evidence base from which a more conclusive judgment can be made for the carcinogenicity of the radio-frequency electromagnetic field.

Prognostic factors in patients undergoing complete resection of pulmonary metastases of colorectal cancer: a multi-institutional cumulative follow-up study.

PURPOSE: The aim of this retrospective study was to establish the prognostic factors for overall survival after pulmonary resection for lung metastases of colorectal carcinoma (CRC). METHODS: The baseline characteristics and outcomes of 266 CRC patients undergoing complete pulmonary resection were collected from 19 institutions by the Japanese Society for Cancer of the Colon and Rectum (JSCCR) Study Group. We used the Cox proportional hazard regression to identify independent prognostic factors for OS. RESULTS: The 5-year overall survival rate of patients undergoing complete resection of isolated pulmonary metastases was 56.5 %. The independent unfavorable prognostic factors after pulmonary resection included stage T4 (p = 0.0004) and N2 (p = 0.0082) as primary cancer-related factors, and more than three metastases (p = 0.0342), bilateral distribution (p = 0.0450), metastatic disease-free interval (DFI) of less than 2 years (p = 0.0257), and a preoperative carcinoembryonic antigen (CEA) level greater than 5.0 ng/mL (p = 0.0209) as pulmonary metastases-related factors. CONCLUSIONS: This retrospective analysis suggested that the indications for pulmonary resection of CRC metastases should be decided not only by the status of lung metastases, but also by pulmonary-related factors such as the T and N stage of the primary lesion, preoperative CEA level, and the DFI.

Estimation of the prevalence of latent abnormalities in the lung and the accuracy of indirect chest x-ray examination among Japanese workers of different age groups.

It is considered that annual chest x-ray (CXR) examination can be restricted to workers by age; however, adequate epidemiological evidence is needed regarding the difference in the effectiveness of CXR examination between younger and older age groups. This study attempted to estimate the prevalence of latent abnormalities (P) in the lung and the false negative rate (F) and false positive rate (G) of examinations among workers of different age groups. 112,482 subjects who were screened for three consecutive years with no findings at the first screening, were selected. The proportion of positive findings at the second screening and the proportion of negative findings at the third screening were incorporated into a stochastic model, and 5-yr-age-specific P, F, and G were estimated. P tended to increase with increasing age. F was 40-45% in <45-yr-old subjects and was only 10% in the older age groups. G showed a steady increase with increasing age. This study indicates that the nature of findings differs between younger and older age groups, and this difference affects the accuracy of examination. In Japan, the age of workers should be considered when a CXR examination is performed.

Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma. Clinical article.

OBJECT: The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme. METHODS: Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done--one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment. RESULTS: The median duration of overall survival was 19.8 [corrected] months (95% CI 13.8-31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3-13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection. CONCLUSIONS: The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.