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.

Adherence to Healthy Dietary Patterns and Glioma: A Matched Case-Control Study.

Recent studies have revealed a putative relationship between diet and glioma development and prognosis, but few studies have examined the association between overall diet and glioma risk. This study, conducted in China, employed a hospital-based case-control approach. The researchers utilized an a priori method based on dietary data to evaluate compliance scores for five healthy dietary patterns (the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diet, the Paleolithic diet, and the Planetary Health Diet) in 1012 participants. At the same time, data-driven methods were used to explore the association between dietary patterns and glioma via principal component analysis (PCA). In the multivariate model, adhering to the Mediterranean diet (odds ratio (OR) = 0.29; 95% confidence interval (95% CI): 0.17-0.52), the DASH diet (OR = 0.09; 95% CI: 0.04-0.18), the MIND diet (OR = 0.25; 95% CI: 0.14-0.44), and the Paleolithic diet (OR = 0.13; 95% CI: 0.06-0.25) was associated with a reduced glioma risk. The results of PCA suggested that increasing the intake of plant-based foods and fish and limiting foods rich in carbohydrates, fats, and salts were associated with a reduced glioma risk. There was a substantial nonlinear dose-response association between glioma and the Mediterranean diet score. However, the DASH diet score, the MIND diet score, and the Paleolithic diet score exhibited linear dose-response relationships. Therefore, this study finds that dietary patterns may be an influencing factor for glioma risk.

Impact of Heavy Metals on Glioma Tumorigenesis.

Recently, an increase in the incidence of brain tumors has been observed in the most industrialized countries. This event triggered considerable interest in the study of heavy metals and their presence in the environment (air, water, soil, and food). It is probable that their accumulation in the body could lead to a high risk of the onset of numerous pathologies, including brain tumors, in humans. Heavy metals are capable of generating reactive oxygen, which plays a key role in various pathological mechanisms. Alteration of the homeostasis of heavy metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and the alteration of proteins. A large number of studies have shown that iron, cadmium, lead, nickel, chromium, and mercury levels were significantly elevated in patients affected by gliomas. In this study, we try to highlight a possible correlation between the most frequently encountered heavy metals, their presence in the environment, their sources, and glioma tumorigenesis. We also report on the review of the relevant literature.

Chinese Dietary Indices and Glioma: New Insights of a Case-Control Study in the Chinese Population.

Identifying modifiable factors in primary prevention strategies is a typical goal of glioma epidemiology. Among many glioma risk factors, diet was always considered as one. Most of the relevant studies thus far were concentrated on the West. It was crucial to investigate the connection between the Chinese diet and gliomas given the stark variations between western and eastern diets. A food frequency questionnaire including 114 items was used to investigate the food intake of the study subjects. The Chinese Dietary Quality Index (CDQI), the Chinese Dietary Balance Index (CDBI), the Dietary Antioxidant Index (DAI), the Dietary Inflammation Index (DII), and the Chinese Healthy Eating Index (CHEI) were calculated based on the data provided by the food frequency questionnaire to evaluate dietary quality, dietary balance, dietary antioxidants, dietary inflammation and adherence to the Chinese dietary guidelines in 506 glioma patients and 506 controls, respectively. After adjusting covariates, CHEI (OR = 0.90, 95% CI: 0.88-0.93) and DAI (OR = 0.61, 95% CI: 0.54-0.70) were correlated to a reduced glioma risk, and CDBI-based undernutrition (OR = 1.08, 95% CI: 1.06-1.12) and overnutrition (OR = 1.14, 95% CI: 1.09-1.20) and DII (OR = 2.20, 95% CI: 1.81-2.68) were correlated to an elevated glioma risk. Moreover, restrictive cubic spline analysis showed that there were significant nonlinear dose-response relationships between CHEI, CDBI, DAI, DII, and glioma. Therefore, adhering to the Chinese dietary guidelines was connected with a lower glioma risk, and undernutrition and overnutrition in the Chinese diet were associated with an increased risk of glioma.

Natural Products for the Immunotherapy of Glioma.

Glioma immunotherapy has attracted increasing attention since the immune system plays a vital role in suppressing tumor growth. Immunotherapy strategies are already being tested in clinical trials, such as immune checkpoint inhibitors (ICIs), vaccines, chimeric antigen receptor T-cell (CAR-T cell) therapy, and virus therapy. However, the clinical application of these immunotherapies is limited due to their tremendous side effects and slight efficacy caused by glioma heterogeneity, antigen escape, and the presence of glioma immunosuppressive microenvironment (GIME). Natural products have emerged as a promising and safe strategy for glioma therapy since most of them possess excellent antitumor effects and immunoregulatory properties by reversing GIME. This review summarizes the status of current immunotherapy strategies for glioma, including their obstacles. Then we discuss the recent advancement of natural products for glioma immunotherapy. Additionally, perspectives on the challenges and opportunities of natural compounds for modulating the glioma microenvironment are also illustrated.

Brain cancer after radiation exposure from CT examinations of children and young adults: results from the EPI-CT cohort study.

BACKGROUND: The European EPI-CT study aims to quantify cancer risks from CT examinations of children and young adults. Here, we assess the risk of brain cancer. METHODS: We pooled data from nine European countries for this cohort study. Eligible participants had at least one CT examination before age 22 years documented between 1977 and 2014, had no previous diagnosis of cancer or benign brain tumour, and were alive and cancer-free at least 5 years after the first CT. Participants were identified through the Radiology Information System in 276 hospitals. Participants were linked with national or regional registries of cancer and vital status, and eligible cases were patients with brain cancers according to WHO International Classification of Diseases for Oncology. Gliomas were analysed separately to all brain cancers. Organ doses were reconstructed using historical machine settings and a large sample of CT images. Excess relative risks (ERRs) of brain cancer per 100 mGy of cumulative brain dose were calculated with linear dose-response modelling. The outcome was the first reported diagnosis of brain cancer after an exclusion period of 5 years after the first electronically recorded CT examination. FINDINGS: We identified 948 174 individuals, of whom 658 752 (69%) were eligible for our study. 368 721 (56%) of 658 752 participants were male and 290 031 (44%) were female. During a median follow-up of 5·6 years (IQR 2·4-10·1), 165 brain cancers occurred, including 121 (73%) gliomas. Mean cumulative brain dose, lagged by 5 years, was 47·4 mGy (SD 60·9) among all individuals and 76·0 mGy (100·1) among people with brain cancer. A significant linear dose-response relationship was observed for all brain cancers (ERR per 100 mGy 1·27 [95% CI 0·51-2·69]) and for gliomas separately (ERR per 100 mGy 1·11 [0·36-2·59]). Results were robust when the start of follow-up was delayed beyond 5 years and when participants with possibly previously unreported cancers were excluded. INTERPRETATION: The observed significant dose-response relationship between CT-related radiation exposure and brain cancer in this large, multicentre study with individual dose evaluation emphasises careful justification of paediatric CTs and use of doses as low as reasonably possible. FUNDING: EU FP7; Belgian Cancer Registry; La Ligue contre le Cancer, L'Institut National du Cancer, France; Ministry of Health, Labour and Welfare of Japan; German Federal Ministry of Education and Research; Worldwide Cancer Research; Dutch Cancer Society; Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat de Catalunya, Spain; US National Cancer Institute; UK National Institute for Health Research; Public Health England.

Body mass index and glioma risk: A prospective multicenter study.

Background: The association between glioma risk and body mass index (BMI) remains obscure. Methods: This study aimed to assess the association between glioma risk and BMI in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The onset of a total of 269 gliomas was observed during a median follow-up period of 12.04 years. Compared with the normal weight, overweight (HR: 1.05; 95% CI: 0.80, 1.39) and obesity (HR: 0.91; 95% CI: 0.56, 1.39) were not significantly associated with glioma risk. Further analysis showed a nonlinear relationship between glioma risk and BMI in men but not women. The multivariable-adjusted HRs per unit increase in BMI were 0.94 (95% CI: 0.89, 1.00; P = 0.037) in men with BMI >25 kg/m2 and 1.16 (95% CI: 0.98, 1.38; P = 0.075) in men with BMI <25 kg/m2. Conclusion: The present data provide evidence that there may be a nonlinear association between BMI and glioma risk in men. The risk of glioma decreased with increasing BMI among men with BMI >25 kg/m2. Future studies are needed to validate our observation.

Trends in brain cancers (glioma) in New Zealand from 1995 to 2020, with reference to mobile phone use.

BACKGROUND: Some case-control studies have suggested substantial increased risks of glioma in association with mobile phone use; these risks would lead to an increase in incidence over time. METHODS: Incidence rates of glioma from 1995 to 2020 by age, sex, and site in New Zealand (NZ) recorded by the national cancer registry were assessed and trends analysed. Phone use was based on surveys. RESULTS: In these 25 years there were 6677 incident gliomas, giving age-standardised rates (WHO world standard) of 6.04 in males, and 3.95 in females per 100,000. The use of mobile phones increased rapidly from 1990 to more than 50% of the population from about 2000, and almost all the population from 2006. The incidence of glioma from ages 10-69 has shown a small decrease over the last 25 years, during which time the use of mobile phones has become almost universal. Rates in the brain locations receiving most radiofrequency energy have also shown a small decrease. Rates at ages of 80 and over have increased. CONCLUSION: There is no indication of any increase related to the use of mobile phones. These results are similar to results in Australia and in many other countries. The increase in recorded incidence at ages over 80 is similar to that seen in other countries and consistent with improved diagnostic methods.

Current Considerations in the Treatment of Grade 3 Gliomas.

OPINION STATEMENT: Treatment recommendations for grade 3 gliomas are guided by their histopathologic and molecular phenotype. In the 2021 WHO classification, these tumors are categorized into two types, grade 3 IDH mutant (IDHmt), 1p/19q codeleted oligodendroglioma and IDH mutant astrocytoma. Treatment consists of maximal safe surgery, followed by radiation therapy (RT) and alkylating agent-based chemotherapy. Based on the updated CATNON result, RT followed by temozolomide improves outcome in patients with non-codeleted grade 3 IDHmt astrocytoma. In patients with IDHmt, codeleted oligodendroglioma, the addition of procarbazine, CCNU, and vincristine regimen is the recommended treatment, based on large randomized controlled trials. These current treatments prolong the overall survival to up to 10 years in patients with grade 3 IDHmt astrocytoma and 14 years in grade 3 IDHmt codeleted oligodendroglioma. Treatment options at recurrence include re-resection, re-irradiation, and other cytotoxic chemotherapy; however, these are of limited benefit. Novel agents targeting IDH mutation and its metabolic effects are currently under investigation to improve the outcome of these patients.

A Single-Center Treatment Experience of Gamma Knife Radiosurgery for Optic Pathway Glioma.

Objectives: To determine the independent prognostic factors that will influence the local tumor control/visual acuity (VA) preservation of optic pathway glioma (OPG) after Gamma Knife radiosurgery (GKS) and to optimize the treatment strategy. Methods: A cohort of 52 consecutive OPG patients who underwent GKS in our center between August 1997 and September 2020 was studied retrospectively. Risk factors such as age at GKS, gender, tumor subtype, tumor site, tumor volume, intratumoral cyst formation, and marginal dose were selected for the univariate and multivariate analysis. COX proportional hazard models were built to determine the independent prognostic factors of local tumor control/VA preservation, and the Kaplan-Meier (K-M) curves were plotted to compare the survival rate among subgroups. Results: 52 OPG patients were included in this study, with a median age of 13.8 years (2-53 years); female outnumbered male at a ratio of 30 : 22; 7 patients (13.5%) had a history of surgical resection; 14 patients (26.9%) were categorized as neurofibromatosis type I (NFI) associated OPG and the rest as sporadic OPG; there were 6 patients (11.5%) with tumors located at hypothalamus/optic chiasm and the rest located in the orbit; the mean tumor volume was 4.36 ml (0.25-11.4 ml); 49 patients (94.2%) presented with VA impairment before GKS; 28 patients (53.8%) underwent single fraction GKS, and the rest underwent fractionated GKS (2-4 fractions); the mean marginal dose (represented with biologically effective dose, BED) was 66.6 Gy (13.3-126.0 Gy); the median follow-up time was 39 months (6-147 months); 11 patients were observed with tumor relapse, 33 with stable disease, and 8 with tumor regression; tumor relapse time varied from 30 to 76 months (mean 54 months); the 1-, 3-, and 5-year progression-free survival (PFS) rates were 100%, 92%, and 78%, respectively; 30 patients were included in the visual analysis; 7 patients were observed with VA deterioration, 19 with stable VA, and 4 with VA improvement; the 1-,3-, and 5-year VA preservation rates were 92%, 84%, and 77%, respectively. COX proportional hazard risk models showed that intratumoral cyst formation and marginal dose were the only two independent prognostic factors of local tumor control/VA preservation; fractionated GKS provided a higher VA preservation rate than single fraction GKS. Four patients were observed with conjunctive edema/conjunctive hyperemia in 1-4 weeks after GKS. Conclusions: GKS is a safe and effective treatment for OPG either as initial treatment or as salvage treatment after surgical resection, it provides good local tumor control and VA preservation, and fractionated GKS could be a preference for OPG patients with baseline VA ≥ 0.2.

Risk factors for pediatric glioma.

Brain tumours are a heterogenic group, a subtype of which is arising from glial cells. Pediatric low-grade gliomas are the most common primary CNS tumour group in childhood, representing 25% to over 30% of pediatric CNS tumours. Pediatric high-grade gliomas are relatively rare and have a poor prognosis. Epidemiological studies have reported various potential risk factors, such as demographics, ionizing and nonionizing radiation, allergic conditions, and infections, immunologic, parental, genetic, and developmental risk factors. These risk factors are relatively unclear and understudied; thus, this narrative review aims to summarize all studies connecting risk factors and pediatric gliomas.

Agricultural activities and risk of central nervous system tumors among French farm managers: Results from the TRACTOR project.

The etiology of central nervous system (CNS) tumors is complex and involves many suspected risk factors. Scientific evidence remains insufficient, in particular in the agricultural field. The goal of our study was to investigate associations between agricultural activities and CNS tumors in the entire French farm manager workforce using data from the TRACTOR project. The TRACTOR project hold a large administrative health database covering the entire French agricultural workforce, over the period 2002-2016, on the whole French metropolitan territory. Associations were estimated for 26 activities and CNS tumors using Cox proportional hazards model, with time to first CNS tumor insurance declaration as the underlying timescale, adjusting for sex, age and geographical area. There were 1017 cases among 1 036 069 farm managers, including 317 meningiomas and 479 gliomas. Associations varied with tumor types, sex and types of crop and animal farming. Analyses showed several increased risks of CNS tumors, in particular for animal farming. The main increases in risk were observed for meningioma in mixed dairy and cow farming (hazard ratio [HR] = 1.75, 95% confidence interval [CI]: 1.09-2.81) and glioma in pig farming (HR = 2.28, 95% CI: 1.37-3.80). Our study brings new insights on the association of a wide range of agricultural activities and CNS tumor and subtype-specific risks in farm managers. Although these findings need to be corroborated in further studies and should be interpreted cautiously, they could have implications for enhancing CNS tumor surveillance in agriculture.

Plasma concentration of Bisphenol A and leptin in patients with meningioma and glioma: A pilot study.

PURPOSE: Recent increase in incidence of meningiomas suggests the need to search for new risk factors. Leptin, a potentially pro-angiogenic and proliferative agent, could be a candidate for this role, as its expression correlates with body mass index (BMI). Because development of meningioma has also been linked to sex hormones, bisphenol A (BPA), a known xenoestrogen, can also be taken into consideration as a potential risk factor. The aim of this study was to determine plasma concentrations of both substances in patients with meningiomas and to match it to patients with gliomas - a group of brain tumors less hormone- and BMI-dependent. MATERIALS & METHODS: Concentrations of BPA and leptin were measured in plasma of 24 patients with low grade meningioma and in 29 patients with glioma, using gas chromatography-mass spectrometry (GC-MS) and ELISA kits, respectively. The concentrations of both substances in patients with neoplasms were interpreted in relation to their concentration in healthy population, published in recent reports. RESULTS: Free and conjugated BPA were present in both meningioma and glioma patients. Moreover, their concentrations far exceeded those reported in the healthy population. Nevertheless, the level of leptin revealed to be significantly higher in meningioma patients than in glioma patients. CONCLUSIONS: Occurrence of both meningioma and glioma may be accompanied by increased concentrations of leptin and BPA. Further large-scale studies are needed to clarify whether the presence of both substances may play a role in pathogenesis or influence clinical course in patients with brain neoplasms.

A Meta-Analysis of Calcium Intake and Risk of Glioma.

BACKGROUND: A meta-analysis was conducted to investigate the correlation between calcium intake and the risk of brain tumors (especially glioma). METHODS: The PubMed, Web of Science, and Embase databases were searched for relevant papers on the association between calcium intake and glioma as of August 22, 2021. The odds ratio (OR) with a 95% confidence interval (CI) was calculated using a random-effects model. Egger's test was conducted to assess publication bias. RESULTS: The meta-analysis includes four studies. The meta-analysis showed that calcium intake and the risk of brain tumors have a significant negative relationship (OR = 0.28; 95% CI: 0.11 to 0.72; P = 0.008). Dose-response analysis showed that for every 100 mg/day increase in calcium intake, the risk of glioma decreased by 7% (OR = 0.93; 95% CI: 0.88 to 0.98). In addition, compared with humans without calcium intake, when calcium intake is 455 mg/day, 800 mg/day and 1000 mg/day, the risk of glioma is 0.65 (95% CI 0.43, 0.97), 0.55 (95% CI 0.37, 0.82) and 0.37 (95% CI 0.15, 0.86). CONCLUSION: There is a significant negative association between calcium intake and brain tumors (especially gliomas), but more high-quality studies are needed to verify these results.

Prospective investigation of herpesvirus infection and risk of glioma.

Glioma is an aggressive neoplasm of the brain with poorly understood etiology. A limited number of pathogens have been examined as glioma risk factors, but data from prospective studies with infection status determined before disease are lacking. Herpesviruses comprise a large family of DNA viruses that infect humans and are linked to a range of chronic diseases. We conducted a prospective evaluation of the association between antibody to six human herpesviruses and glioma risk in the Janus Serum Bank (Janus) and the Cancer Prevention Study-II (CPS-II). In Janus and CPS-II, the risk for glioma was not related to seroprevalence of herpes simplex virus-1, varicella zoster virus, or human herpes viruses 6A or 6B. In Janus, seropositivity to either the Epstein Barr virus (EBV) EA[D] or VCAp18 antigen was associated with a lower risk of glioma (ORs: 0.55 [95% CI 0.32-0.94] and 0.57 [95% CI 0.38-0.85]). This inverse association was consistent by histologic subtype and was observed for gliomas diagnosed up to two decades following antibody measurement. In Janus, seropositivity to at least one of three examined cytomegalovirus (CMV) antigens (pp150, pp52, pp28) was associated with an increased risk of nonglioblastoma (OR: 2.08 [95% CI 1.07-4.03]). This association was limited to tumors diagnosed within 12 years of antibody measurement. In summary, we report evidence of an inverse association between exposure to EBV and glioma. We further report that CMV exposure may be related to a higher likelihood of the nonglioblastoma subtype.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Pre-diagnostic levels of sVEGFR2, sTNFR2, sIL-2Rα and sIL-6R are associated with glioma risk: A nested case-control study of repeated samples.

No strong aetiological factors have been established for glioma aside from genetic mutations and variants, ionising radiation and an inverse relationship with asthmas and allergies. Our aim was to investigate the association between pre-diagnostic immune protein levels and glioma risk. We conducted a case-control study nested in the Northern Sweden Health and Disease Study cohort. We analysed 133 glioma cases and 133 control subjects matched by age, sex and date of blood donation. ELISA or Luminex bead-based multiplex assays were used to measure plasma levels of 19 proteins. Conditional logistic regression models were used to estimate the odds ratios and 95% CIs. To further model the protein trajectories over time, the linear mixed-effects models were conducted. We found that the levels of sVEGFR2, sTNFR2, sIL-2Rα and sIL-6R were associated with glioma risk. After adjusting for the time between blood sample collection and glioma diagnosis, the odds ratios were 1.72 (95% CI = 1.01-2.93), 1.48 (95% CI = 1.01-2.16) and 1.90 (95% CI = 1.14-3.17) for sTNFR2, sIL-2Rα and sIL-6R, respectively. The trajectory of sVEGFR2 concentrations over time was different between cases and controls (p-value = 0.031), increasing for cases (0.8% per year) and constant for controls. Our findings suggest these proteins play important roles in gliomagenesis.

Pesticide Residue Intake From Fruit and Vegetable Consumption and Risk of Glioma.

We aimed to determine whether intake of pesticide residues from fruits and vegetables was associated with glioma. Within 3 prospective cohorts from 1998-2016-the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and Health Professionals Follow-up Study-we computed multivariable-adjusted hazard ratios (MVHRs) and 95% confidence intervals (CI) for glioma by quintiles of intake of low- and high-pesticide-residue fruits and vegetables using Cox proportional hazards regression. Fruits and vegetables were categorized as high or low residue using a validated method based on pesticide surveillance data. We confirmed 275 glioma cases across 2,745,862 person-years. A significant association was observed between intake of high-residue fruits and vegetables and glioma in NHS (MVHR = 2.99, 95% CI: 1.38, 6.44 comparing highest with lowest quintile, P for trend = 0.02). This was not identified in NHSII (MVHR = 0.52, 95% CI: 0.19, 1.45, P for trend = 0.20) or Health Professionals Follow-up Study (MVHR = 1.01, 95% CI: 0.42, 2.45, P for trend = 0.39). No significant associations were observed by intake of low-residue fruits and vegetables; overall intake was not significantly associated with glioma in any cohort. We found no evidence for an inverse relationship of fruit and vegetable intake with glioma. Although limited in power, this study suggests a possible association between fruit-and-vegetable pesticide residue intake and risk of glioma that merits further study.

EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3.

BACKGROUND: Gliomas are the most common malignant primary brain tumours with a highly immunosuppressive tumour microenvironment (TME) and poor prognosis. Circular RNAs (circRNA), a newly found type of endogenous noncoding RNA, characterized by high stability, abundance, conservation, have been shown to play an important role in the pathophysiological processes and TME remodelling of various tumours. METHODS: CircRNA sequencing analysis was performed to explore circRNA expression profiles in normal and glioma tissues. The biological function of a novel circRNA, namely, circNEIL3, in glioma development was confirmed both in vitro and in vivo. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation (RIP), luciferase reporter, and co-immunoprecipitation assays were conducted. RESULTS: We identified circNEIL3, which could be cyclized by EWS RNA-binding protein 1(EWSR1), to be upregulated in glioma tissues and to correlate positively with glioma malignant progression. Functionally, we confirmed that circNEIL3 promotes tumorigenesis and carcinogenic progression of glioma in vitro and in vivo. Mechanistically, circNEIL3 stabilizes IGF2BP3 (insulin-like growth factor 2 mRNA binding protein 3) protein, a known oncogenic protein, by preventing HECTD4-mediated ubiquitination. Moreover, circNEIL3 overexpression glioma cells drives macrophage infiltration into the tumour microenvironment (TME). Finally, circNEIL3 is packaged into exosomes by hnRNPA2B1 and transmitted to infiltrated tumour associated macrophages (TAMs), enabling them to acquire immunosuppressive properties by stabilizing IGF2BP3 and in turn promoting glioma progression. CONCLUSIONS: This work reveals that circNEIL3 plays a nonnegligible multifaceted role in promoting gliomagenesis, malignant progression and macrophage tumour-promoting phenotypes polarization, highlighting that circNEIL3 is a potential prognostic biomarker and therapeutic target in glioma.