Risk Of Brain Tumors Research Articles

CNSC-19. ISCHEMIC STROKE DRIVES GLIOMA PROGRESSION BY REMODELING TUMOR-ASSOCIATED ASTROCYTES

Abstract Ischemic stroke and glioma are two deadly neurological disorders worldwide. Recent epidemiological studies reveal an increased risk of brain tumors, notably glioma, in patients with a history of stroke, resulting in a 10% co-occurrence. Comparative transcriptome analyses of brain samples collected from patients with common neurological disorders show that glioma is particularly enriched with stroke-associated gene signatures, especially in pathways related to their shared pathological features. These findings suggest a stroke-glioma interrelationship; however, it remains unknown how stroke alters the brain microenvironment to drive tumor progression. Here, we induced photothrombotic stroke in three mouse glioma models recapitulating multiple aspects of human glioma. Across all glioma models, we consistently observed that stroke increases tumor proliferation and infiltration towards stroke-affected regions, accompanied by reduced survival compared to sham control groups. Further analyses using single-cell RNA sequencing and spatial transcriptomic profiling in our stroke-glioma models reveal pronounced stroke-induced glioma microenvironment changes, among which tumor-associated astrocytes (TAAs) are most dramatically remodeled. Remarkably, we identified a unique stroke-induced astrocyte (SAA) at the tumor leading edge of the stroke-glioma group, characterized by diminished physiological astrocyte signatures and increased chromosomal and metabolic reprogramming. Among the top differentially expressed genes in SAA compared with TAA, the sodium-bicarbonate cotransporter Slc4a4 is interesting due to its enriched expression in TAA in both human and mouse gliomas, and it is significantly down-regulated at the infiltrating tumor edge. Consequently, we examine whether restoring astrocytic Slc4a4 expression rescues stroke-induced glioma progression. We found that astrocytic Slc4a4 overexpression reduces glioma growth and infiltration, accompanied by extended astroglial scar formation. Collectively, our study demonstrates that a subset of TAAs induced by stroke exacerbates glioma pathology, highlighting an indispensable astrocytic contribution to the stroke-glioma interaction.

CSIG-06. BRAF GERMLINE MUTATIONS AND PREDISPOSITION TO BRAIN TUMORS

Abstract We report on two BRAF-mutated children and discuss genetic counseling regarding predisposition to brain tumors. Molecular analysis of the PTPN11 gene and twelve other genes in the RAS-MAPK pathway was carried out in a series of 54 dysmorphic patients with suspected Rasopathies. Two heterozygous BRAF germline mutations were detected in two 7-year-old girls, at exon 6 and 12 respectively. Both patients had the distinctive facial appearance of cardio-facio-cutaneous syndrome (CFC) type 1. Patients with CFC are rare and characterized by phenotypic and genetic heterogeneity, with overlaps with Noonan syndrome. While nearly 75% of CFC cases have germline BRAF mutations, the frequency of BRAF mutations is inferior in Noonan and LEOPARD syndromes. BRAF mutations in CFC are often found in the cysteine-rich domain of the BRAF protein (exons 6, 11, 12, 13, 14, 15 and 16). Conversely, somatic BRAF mutations are more common, grouped into classes according to their kinase activity level, and have been associated with a variety of malignancies, including pediatric and adult brain tumors (low- and high-grade gliomas, glioblastomas and low-grade astrocytomas). BRAF V600E is the most common somatic mutation, but other mutations are currently being identified. Many of these mutations are within the kinase domain, while others are located across the gene and have less well-understood functional consequences. Germinal V600E mutation has been described once, in a CFC patient having a severe phenotype. Nevertheless, it seems that patients with germline BRAF mutations and gliomas have not yet been reported. Given the rarity of CFC, it is unclear whether there is a high risk of brain tumors. Further molecular studies will enable us to refine recommendations for the prevention, monitoring and care of people with germline BRAF mutations, given the success of BRAF inhibitors in certain cancers, with encouraging results in gliomas.

Cancer Risk in Patients With Muscular Dystrophy and Myotonic Dystrophy: A Register-Based Cohort Study.

Muscular dystrophies and myotonic disorders are genetic disorders characterized by progressive skeletal muscle degeneration and weakness. Epidemiologic studies have found an increased cancer risk in myotonic dystrophy, although the cancer risk spectrum is poorly characterized. In patients with muscular dystrophy, the cancer risk is uncertain. We aimed to determine the overall cancer risk and cancer risk spectrum in patients with muscular dystrophy and myotonic dystrophy using data from the Swedish National registers. We performed a matched cohort study in all patients with muscular dystrophy or myotonic dystrophy born in Sweden 1950-2017 and 50 matched comparisons by sex, year of birth, and birth county per individual. The association with cancer overall and specific malignancies was estimated using stratified Cox proportional hazard models. We identified 2,355 and 1,968 individuals with muscular dystrophy and myotonic dystrophy, respectively. No increased overall cancer risk was found in muscular dystrophy. However, we observed an increased risk of astrocytomas and other gliomas during childhood (hazard ratio [HR] 8.70, 95% CI 3.57-21.20) and nonthyroid endocrine cancer (HR 2.35, 95% CI 1.03-5.34) and pancreatic cancer (HR 4.33, 95% CI 1.55-12.11) in adulthood. In myotonic dystrophy, we found an increased risk of pediatric brain tumors (HR 3.23, 95% CI 1.16-9.01) and an increased overall cancer risk in adults (HR 2.26, CI 1.92.2.66), specifically brain tumors (HR 10.44, 95% CI 7.30-14.95), thyroid (HR 3.92, 95% CI 1.70-9.03), and nonthyroid endocrine cancer (HR 7.49, 95% CI 4.47-12.56), endometrial (HR 8.32, 95% CI 4.22-16.40), ovarian (HR 4.00, 95% CI 1.60-10.01), and nonmelanoma skin cancer (HR 3.27, 95% CI 1.32-8.13). Here, we analyze the cancer risk spectrum of patients with muscular dystrophy and myotonic dystrophy. To the best of our knowledge, this is the first report of an increased risk for CNS tumors in childhood and adult nonthyroid endocrine and pancreatic cancer in muscular dystrophy. Furthermore, for myotonic dystrophy, we confirmed previously reported associations with cancer and expanded the cancer spectrum, finding an unreported increased risk for nonthyroid endocrine cancer. Additional studies confirming the cancer risk and delineating the cancer spectrum in different genetic subtypes of muscular dystrophies are warranted before considering altered cancer screening recommendations than for the general population.

Revealing the link between gut microbiota and brain tumor risk: a new perspective from Mendelian randomization.

Recent studies have shown that gut microbiota may be related to the occurrence of brain tumors, but direct evidence is lacking. This study used the Mendelian randomization study (MR) method to explore the potential causal link between gut microbiota and brain tumors. We analyzed the genome-wide association data between 211 gut microbiota taxa and brain tumors, using the largest existing gut microbiota Genome-Wide Association Studies meta-analysis data (n=13266) and combining it with brain tumor data in the IEU OpenGWAS database. We use inverse-variance weighted analysis, supplemented by methods such as Mendelian randomization-Egger regression, weighted median estimator, simple mode, and weighted mode, to assess causality. In addition, we also conducted the Mendelian randomization-Egger intercept test, Cochran's Q test, and Mendelian randomization Steiger directionality test to ensure the accuracy of the analysis. Quality control includes sensitivity analysis, horizontal gene pleiotropy test, heterogeneity test, and MR Steiger directionality test. Our study found that specific gut microbial taxa, such as order Lactobacillales and family Clostridiaceae1, were positively correlated with the occurrence of brain tumors, while genus Defluviitaleaceae UCG011 and genus Flavonifractor were negatively correlated with the occurrence of brain tumors. The Mendelian randomization-Egger intercept test showed that our analysis was not affected by pleiotropy (P>0.05). This study reveals for the first time the potential causal relationship between gut microbiota and brain tumors, providing a new perspective for the prevention and treatment of early brain tumors. These findings may help develop new clinical intervention strategies and point the way for future research.

Risk of new tumor, carotid stenosis, and stroke after Stereotactic Radiosurgery for Pituitary Tumor: A multicenter study of 2254 patients with imaging follow-up.

Higher risk of secondary brain tumor, carotid stenosis and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion and stroke after SRS. In this multicentric retrospective study, 2,254 patients with PitNET were studied, 1,377 in the exposed group and 877 in the control group. There were 9,840.1 patient-years at risk for the SRS and 5,266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95%CI:0.5%, 4.1%) for SRS and 3.7% (95%CI:0%, 8.7%) for the control group (p=0.6), with an incidence rate of 1.32 per 1,000 and 0.95 per 1,000, respectively. SRS was not associated with increased risk of tumorigenesis when stratified by age (HR: 1.59 [95%CI: 0.57, 4.47], p=0.38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95%CI: 0.2, 1.6) in the SRS and 2% (95%CI: 0, 4.4) in the control group (p=0.8). The 15-year probability of stroke was 2.6% (95%CI: 0.6%, 4.6%) in the SRS and 11.1% (95%CI: 6%, 15.9%) in the control group (p<0.001). In cox multivariate analysis stratified by age, SRS (HR 1.85[95%CI:0.64, 5.35], p=0.26) was not associated with risk of new stroke. No increased risk of long-term secondary brain tumor, new stenosis or occlusion and stroke was demonstrated in SRS group compared to control in this study with imaging surveillance.

Germline pathogenic variants in the MRE11, RAD50, and NBN (MRN) genes in cancer predisposition: A systematic review and meta-analysis.

The MRE11, RAD50, and NBN genes encode the MRN complex sensing DNA breaks and directing their repair. While carriers of biallelic germline pathogenic variants (gPV) develop rare chromosomal instability syndromes, the cancer risk in heterozygotes remains controversial. We performed a systematic review and meta-analysis of 53 studies in patients with different cancer diagnoses to better understand the cancer risk. We found an increased risk (odds ratio, 95% confidence interval) for gPV carriers in NBN for melanoma (7.14; 3.30-15.43), pancreatic cancer (4.03; 2.14-7.58), hematological tumors (3.42; 1.14-10.22), and prostate cancer (2.44, 1.84-3.24), but a low risk for breast cancer (1.29; 1.00-1.66) and an insignificant risk for ovarian cancer (1.53; 0.76-3.09). We found no increased breast cancer risk in carriers of gPV in RAD50 (0.93; 0.74-1.16; except of c.687del carriers) and MRE11 (0.87; 0.66-1.13). The secondary burden analysis compared the frequencies of gPV in MRN genes in patients from 150 studies with those in the gnomAD database. In NBN gPV carriers, this analysis additionally showed a high risk for brain tumors (5.06; 2.39-9.52), a low risk for colorectal (1.64; 1.26-2.10) and hepatobiliary (2.16; 1.02-4.06) cancers, and no risk for endometrial, and gastric cancer. The secondary burden analysis showed also a moderate risk for ovarian cancer (3.00; 1.27-6.08) in MRE11 gPV carriers, and no risk for ovarian and hepatobiliary cancers in RAD50 gPV carriers. These findings provide a robust clinical evidence of cancer risks to guide personalized clinical management in heterozygous carriers of gPV in the MRE11, RAD50, and NBN genes.

Maternal smoking, consumption of alcohol, and caffeinated beverages during pregnancy and the risk of childhood brain tumors: a meta-analysis of observational studies

BackgroundWe conducted this meta-analysis to investigate the potential association between maternal smoking, alcohol and caffeinated beverages consumption during pregnancy and the risk of childhood brain tumors (CBTs).MethodsA thorough search was carried out on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Internet to identify pertinent articles. Fixed or random effects model was applied to meta-analyze the data.ResultsThe results suggested a borderline statistically significant increased risk of CBTs associated with maternal smoking during pregnancy (OR 1.04, 95% CI 0.99–1.09). We found that passive smoking (OR 1.12, 95% CI 1.03–1.20), rather than active smoking (OR 1.00, 95% CI 0.93–1.07), led to an increased risk of CBTs. The results suggested a higher risk in 0–1 year old children (OR 1.21, 95% CI 0.94–1.56), followed by 0–4 years old children (OR 1.12, 95% CI 0.97–1.28) and 5–9 years old children (OR 1.11, 95% CI 0.95–1.29). This meta-analysis found no significant association between maternal alcohol consumption during pregnancy and CBTs risk (OR 1.00, 95% CI 0.80–1.24). An increased risk of CBTs was found to be associated with maternal consumption of caffeinated beverages (OR 1.16, 95% CI 1.07–1.26) during pregnancy, especially coffee (OR 1.18, 95% CI 1.00–1.38).ConclusionsMaternal passive smoking, consumption of caffeinated beverages during pregnancy should be considered as risk factors for CBTs, especially glioma. More prospective cohort studies are warranted to provide a higher level of evidence.

Impact of Radiofrequency Exposure From Mobile Phones on the Risk of Developing Brain Tumors in Korean and Japanese Adolescents: A MOBI-Kids Case-control Study.

This study aimed to examine the association between risk of brain tumors and radiofrequency (RF) exposure from mobile phones among young people in Korea and Japan. This case-control study of brain tumors in young people was conducted in Korea and Japan under the framework of the international MOBI-Kids study. We included 118 patients diagnosed with brain tumors between 2011 and 2015 and 236 matched appendicitis controls aged 10-24 years. Information on mobile phone use was collected through face-to-face interviews. A detailed RF exposure algorithm, based on the MOBI-Kids algorithm and modified to account for the specificities of Japanese and Korean phones and networks, was used to calculate the odds ratios (ORs) for total cumulative specific energy using conditional logistic regression. The adjusted ORs in the highest tertile of cumulative call time at 1 year before the reference date were 1.61 (95% confidence interval [CI], 0.72-3.60) for all brain tumors and 0.70 (95% CI, 0.16-3.03) for gliomas, with no indication of a trend with exposure. The ORs for glioma specifically, were below 1 in the lowest exposure category. This study provided no evidence of a causal association between mobile phone use and risk of brain tumors as a whole or of glioma specifically. Further research will be required to evaluate the impact of newer technologies of communication in the future.

Sex-specific functional effect of IL-12 gene polymorphisms in brain tumours

The role of the IL-12 family cytokines in brain tumourigenesis is an active area of research, but only a few studies have explored the impact of the functional IL12B polymorphisms on brain tumour (BT) risk. The present study aimed to evaluate the possible impact and functional effect of IL12B rs3212227 and rs17860508 on BT susceptibility in adults. We observed a lower frequency of the C-allele variant of the rs3212227 polymorphism among cases with primary BT compared to those with brain metastasis (BrM) and individuals with no benign or malignant tumours under allelic and dominant genetic models. The frequency of the C-allele of rs3212227 was significantly lower in primary BT cases than in controls (16% vs. 26.5% with OR = 0.529, 95%CI: 0.3–0.94, p = .029; ORadjusted=0.442; 95%CI: 0.23–0.87; p = .018). There was no significant association between rs17860508 and BT risk under all analysed genetic models after age and sex adjustment. A significantly higher IL-12p40 serum level in men with primary BT than in women (p = .0007) was found. We observed a sex-specific effect of rs3212227 polymorphism on serum IL-12p40 levels in cases with primary BT in contrast to BrM. The C-allele carriership was associated with higher IL-12p40 in women with primary BT. Serum levels of IL-23 were similar across the patients’ subgroups. The obtained results suggest that the IL12B rs3212227 polymorphism influences the risk for primary BT in contrast to rs17860508 polymorphism and shows a sex-specific functional effect on IL-12p40 levels. Also, the male gender was associated with higher IL-12p40 in cases with primary BT.

Associations of PD-1 and PD-L1 gene polymorphisms with cancer risk: a meta-analysis based on 50 studies.

Programmed death-1 and its ligand-1 (PD-1/PD-L1), immune checkpoints proteins, play a crucial role in anti-tumor responses. A large number of studies have evaluated the relationships of PD-1/PD-L1 polymorphisms with risk of cancer, but evidence for the associations remains inconsistent. Therefore, we performed a meta-analysis to examine the associations between PD-1/PD-L1 single nucleotide polymorphisms (SNPs) and cancer predisposition. Results showed that PD-1.3 and PD-L1 rs17718883 were significantly correlated with overall cancer risk. PD-1.5 was prominently linked with cervical cancer (CC), non-small cell lung cancer (NSCLC), TC (thyroid cancer), brain tumor, AML (acute myelocytic leukemia) and UCC (urothelial cell carcinoma) risk, PD-1.9 with breast cancer (BC), AML, esophageal cancer (EC) and ovarian cancer (OC) risk, and PD-1.3 with colorectal cancer (CRC) and BCC (basal cell carcinoma) risk. PD-1.1 polymorphism slightly elevated BC and OC susceptibility, whereas the rs4143815 variant notably decreased the risk of gastric cancer (GC), hepatocellular carcinoma (HCC) and OC, but increased the risk of BC. PD-1.6 was closely linked with AML risk, PD-L1 rs2890658 with NSCLC, HCC and BC risk, rs17718883 with HCC and GC risk, rs10815225 with GC risk, and rs2297136 with NSCLC and HCC risk. Interestingly, the rs7421861, rs10815225, and rs10815225 markedly reduced cancer susceptibility among Asians. The rs7421861 polymrophism decreased cancer risk among Caucasians, rather than the rs10815225 elevated cancer risk. Our results supported that PD-1 and PD-L1 SNPs were dramatically correlated with cancer risk.

Abstract PR-009: Associations between PM2.5, vegetation density and childhood brain tumors: a case-control registry-based study from Texas 1995-2011

Abstract Background: Air pollution has been reported to be associated with some childhood cancers, namely leukemias. Less is known about air pollution and childhood brain tumor risk. In adult cancers, increasing vegetation density, or greenness, has been inversely associated with cancer incidence and survival. The interplay between air pollution and greenness, which co-occur, in childhood cancer etiology is unclear. Therefore, we sought to estimate the association between prenatal and early life exposure to air pollution, greenness, and childhood cancer in Texas (1995-2011). Materials and Methods: We included 1,316 individuals with a childhood brain tumor diagnosed &amp;lt;17 years of age and 109,762 age- and sex-matched controls. We linked birth certificate residential address to census tract annual average particulate matter 2.5 µg/m³ (PM2.5) and Normalized Difference Vegetation Index (NDVI) to approximate prenatal and early life exposure to greenness and air pollution. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) as the measure of association between PM2.5 and NDVI interquartile range (IQR) increases and brain tumors. Models were adjusted for birth year, sex, maternal race/ethnicity, and area-level socioeconomic status (Yost index). Results: The following brain tumor types were included: ependymoma (n=136), astrocytoma (n=619), medulloblastoma (n=187), PNET (n=57), ATRT (n=54), and other gliomas (n=263). Average birth year PM2.5 and NDVI exposure levels were similar in cases and controls, 11 µg/m³ and 0.4, respectively. Each IQR increase (2.6 µg/m³) in PM2.5 was associated with ependymoma (OR: 1.27, 95% CI: 1.01-1.60) when adjusting for control-derived quartiles of NDVI. Conversely, after adjusting for PM2.5 quartiles, each IQR increase in NDVI (0.13) was inversely associated with ependymoma in those diagnosed at 0-4 years of age (OR: 0.75, 95% CI: 0.56-0.97) and with medulloblastoma in those aged 0-16 years at diagnosis (OR: 0.75, 95% CI: 0.62-0.91). There was no evidence of statistical interaction between NDVI and PM2.5 (all Likelihood Ratio Test p-values&amp;gt;0.05) for any brain tumors. Conclusions: Increasing residential air pollution during prenatal and early life increased the risk of childhood ependymoma in Texas independent of greenness. Conversely, increasing greenness exposure in prenatal and early life decreased the risk of ependymoma and medulloblastoma independent of PM2.5. These findings highlight the complex relationship between air pollution and greenness in childhood cancer etiology. Citation Format: Lindsay Williams, David Haynes, Jeannette Sample, Laura McGuinn, Thanh Hoang, Philip Lupo, Michael Scheurer. Associations between PM2.5, vegetation density and childhood brain tumors: a case-control registry-based study from Texas 1995-2011 [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr PR-009.

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

BackgroundEach 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. MethodsWe 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. Results264,574 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). ConclusionsOur findings suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma.

Ocular Motor Cranial Nerve Palsies and Increased Risk of Primary Malignant Brain Tumors: South Korean National Health Insurance Data.

The aim of this study was to investigate the association between ocular motor cranial nerve palsies (OMCNP) and the occurrence of primary malignant brain tumors in a Korean population, using the national sample cohort database from Korea National Health Insurance Service (KNHIS). KNHIS data between 2010 and 2017 were analyzed. Our sample encompassed 118,686 participants, including 19,781 from a recently diagnosed OMCNP cohort and 98,905 from a matched control cohort through a 1:5 propensity score matching based on age and gender. To counteract the issue of reverse causation, we integrated a one-year time lag in our sensitivity analysis. Study participants were followed up until 31 December 2019. Cox proportional hazard regression analysis was used to compute the adjusted hazard ratio (HR) for primary malignant brain tumors according to the OMCNP diagnosis. Additionally, we performed a subgroup analysis to discern effects of various factors on the association between OMCNP and primary malignant brain tumors. HR for primary malignant brain tumors was 3.272 (95% confidence interval [CI]: 2.294 to 4.665) in the OMCNP cohort compared to the control cohort in a fully adjusted model for age, sex, socio-economic status, smoking, drinking, regular physical exercise, hypertension, diabetes, dyslipidemia, obesity, chronic kidney disease, and human immunodeficiency virus infection. Further subgroup analysis revealed that the risk of primary malignant brain tumors was significantly increased in women with OMCNP compared to men with OMCNP (HR: 5.118 in women vs. 2.441 in men, p = 0.0440), and in those aged <65 years than in those aged ≥65 years (HR: 6.951 in age < 65 years vs. 1.899 in age ≥ 65 years, p = 0.0006). Our population-based cohort study demonstrated a significantly increased risk of subsequent primary malignant brain tumors in patients with OMCNP. Particularly, OMCNP-afflicted women aged below 65 manifested a heightened probability of developing primary malignant brain tumors compared to those devoid of OMCNP.

Use of drugs for hyperlipidaemia and diabetes and risk of primary and secondary brain tumours: nested case–control studies using the UK Clinical Practice Research Datalink (CPRD)

ObjectivesPrevious studies have suggested that fibrates and glitazones may have a role in brain tumour prevention. We examined if there is support for these observations using primary care records from...

Maternal and Perinatal Factors Associated With Childhood Brain Tumors: A Case-Control Study in Vietnam.

Brain cancer is the leading cause of cancer-related deaths in children and the majority of childhood brain tumors are diagnosed without determination of their underlying etiology. Little is known about risk factors for childhood brain tumors in Vietnam. The objective of this case-control study was to identify maternal and perinatal factors associated with brain tumors occurring in young Vietnamese children and adolescents. We conducted a hospital-based case-control study at Viet Duc University Hospital in Hanoi, Vietnam. Cases consisted of children with brain tumors aged 0-14years old admitted to the hospital from January 2020 to July 2022 while the controls were age and sex-matched hospitalized children diagnosed with head trauma. Perinatal characteristics were abstracted from hospital medical records and maternal medical, behavioral, and sociodemographic factors were collected through in-person interviews. Conditional logistic regression models were used to examine maternal and perinatal factors associated with childhood brain tumors. The study sample included 220 children (110 cases and 110 controls) whose average age was 8.9 years and 41.8% were girls. Children born to mothers aged greater than 30 years at the time of the child's birth had a higher risk of childhood brain tumors compared to those born to mothers aged from 18 to 30 years old (OR = 2.55; 95% CI: 1.13-5.75). Additionally low maternal body mass index prior to the current pregnancy of <18.5kg/m2 significantly increased the odds of having a child with a brain tumor in relation to normal maternal body mass index from 18.5-22.9kg/m2 (OR = 3.19; 95% CI: 1.36 - 7.50). Advanced maternal age and being markedly underweight were associated with an increased odds of having a child with a brain tumor. A population-based study with larger sample size is needed to confirm and extend the present findings.

Association between the Use of Statins and Brain Tumors.

This study aimed to investigate the effects of statin use on the incidence of brain tumors. The Korean National Health Insurance Service-National Sample Cohort from 2005 to 2019 was used. The 1893 patients who were diagnosed with brain tumors were matched with 7572 control patients for demographic variables. The history of dyslipidemia was collected, and their history of prescription of statins before diagnosis of brain tumor was examined. The participants without dyslipidemia were set as a reference population. Then, the odds for brain tumors were analyzed in dyslipidemia patients without statin use, dyslipidemia patients who were prescribed statins for less than 365 days, and dyslipidemia patients who were prescribed statins for 365 days or more. Propensity score overlap weighted multivariable logistic regression analysis was used and adjusted for demographics and comorbidities. Secondary analyses were conducted according to types of statins, malignancy of brain tumors, and histories of demographics or comorbidities. A total of 11.78% of brain tumor patients and 10.95% of control participants had histories of statin use for 365 days or more. Dyslipidemia patients with 365 days or more duration of statin use demonstrated 1.22 times higher odds for brain tumors than normal participants (95% confidence intervals [CI] = 1.06-1.14, p = 0.007). Dyslipidemia patients with less than 365 days of statin use had higher odds of brain tumors than other groups (odds ratio = 1.60, 95% CI = 1.36-1.87, p < 0.001). The higher odds for brain tumors in short-term statin users (<365 days) than in long-term statin users (≥365 days) were consistent in secondary analyses according to types of statins, malignancy of brain tumors, and histories of demographics or comorbidities. Long-term statin use in dyslipidemia patients was related to a lower risk of brain tumors than short-term statin use in patients with dyslipidemia.

Research of Pesticide Metabolites in Human Brain Tumor Tissues by Chemometrics-Based Gas Chromatography-Mass Spectrometry Analysis for a Hypothetical Correlation between Pesticide Exposure and Risk Factor of Central Nervous System Tumors.

Pesticides are widely used, resulting in continuing human exposure with potential health impacts. Some exposures related to agricultural works have been associated with neurological disorders. Since the 2000s, the hypothesis of the role of pesticides in the occurrence of central nervous system (CNS) tumors has been better documented in the literature. However, the etiology of childhood brain cancers still remains largely unknown. The major objective of this work was to assess the potential role of pesticide exposure as a risk factor for CNS tumors based on questionnaires and statistical analysis of information collected from patients hospitalized in the Neurosurgery Department of the Habib Bourguiba Hospital Medium in Sfax, Tunisia, during the period from January 1, 2022, to May 31, 2023. It also aimed to develop a simple and rapid analytical method by the gas chromatography-mass spectrometry technique for the research traces of pesticide metabolites in some collected human brain tumor tissues in order to more emphasize our hypothesis for such a correlation between pesticide exposure and brain tumor development. Patients with a history of high-risk exposure were selected to conduct further analysis. Chemometric methods were adapted to discern intrinsic variation between pathological and control groups and ascertain effective separation with the identification of differentially expressed metabolites accountable for such variations. Three samples revealed traces of pesticide metabolites that were mostly detected at an early age. The histopathological diagnosis was medulloblastoma for a 10-year-old child and high-grade gliomas for 27- and 35-year-old adults. The bivariate analyses (odds ratio >1 and P value <5%) confirmed the great probability of developing cancer by an exposure case. The Cox proportional hazards model revealed the risk of carcinogenicity beyond the age of 50 as a long-term effect of pesticide toxicity. Our study supports the correlation between pesticide exposure and the risk of development of human brain tumors, suggesting that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased childhood brain tumor risk. This hypothesis was enhanced in identifying traces of metabolites from the carbamate insecticide class known for their neurotoxicity and others from pyridazinone, organochlorines (OCs), triazole fungicide, and N-nitroso compounds known for their carcinogenicity. The 2D-OXYBLOT analysis confirmed the neurotoxicity effect of insecticides to induce oxidative damage in CNS cells. Aldicarb was implicated in brain carcinogenicity confirmed by the identification of oxime metabolites in a stress degradation study. Revealing "aziridine" metabolites from the OC class may better emphasize the theory of detecting traces of pesticide metabolites at an early age. Overall, our findings lead to the recommendation of limiting the residential use of pesticides and the support of public health policies serving this objective that we need to be vigilant in the postmarketing surveillance of human health impacts.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6months and in meta-analyses. Our data suggest that breastfeeding does not protect against CBT.

The Relationship between Air Pollution and Brain Cancer: A Systematic Review and Meta-Analysis.

There is very little epidemiological evidence on the effects of ambient air pollution on brain tumor risk. The purpose of this study was to determine the relationship between exposure to air pollution and the incidence of brain tumors. A comprehensive literature search in five international databases, including PubMed/Medline, ProQuest, Scopus, Embase, and ISI/WOS on April 15, 2019, was conducted. The methodology of the present study was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. The Newcastle-Ottawa Quality Assessment Form was used to evaluate the quality of the selected papers. Five studies that measured adult brain tumors as well as their long-term exposure to at least one of the pollutants criteria for air pollution, PM2.5 absorbance, and proximity to traffic (Trafnear) were reviewed. The results showed that the pooled relative risk (RR) for incidence of brain tumor and long term exposure to Trafnear, PM2.5, PM2.5 absorbance, O3 and NOx were RR = 1.07, (95% CI 0.99-1.16), P = 0.079, for Trafnear; RR = 0.90, (95% CI 0.80-1.00), P = 0.064 for PM2.5; RR = 1.63, (95% CI 1.04-2.55), P = 0.031 for PM2.5 absorbance; RR = 1.3, (95% CI 1.03-1.6), P = 0.023 for O3; and RR = 1.16, (95% CI 0.93-1.45), P = 0.173 for NOx. Exposure to other air pollutants had no statistically significant association with brain tumor incidence. The results showed that exposure to air pollutants, such as O3 and PM2.5 absorbance, had the highest correlation with brain tumor incidence. They also showed an absence of correlation between exposure to certain pollutants (SO2, CO, NO2, PM10, PM2.5) and brain tumor incidence.

Maternal and childhood medical history and the risk of childhood brain tumours: a case-control study in Ontario, Canada.

Studies to date have yielded inconclusive results as to whether maternal medical history during pregnancy, and a child's early-life medical history contribute to the development of childhood brain tumours (CBTs). This study examined associations between maternal and childhood medical history and the risk of CBTs. The Childhood Brain Tumour Epidemiology Study of Ontario (CBREO) examined children 0-15 years of age with newly diagnosed CBTs from 1997 to 2003. Multivariable logistic regression analysis determined associations for prenatal medications and childhood medical history, adjusted for child's demographics, and maternal education. Analyses were stratified by histology. A latency period analysis was conducted using 12- and 24-month lead times. Maternal intake of immunosuppressants during the prenatal period was significantly associated with glial tumours (OR 2.73, 95% CI 1.17-6.39). Childhood intake of anti-epileptics was significantly associated with CBTs overall, after accounting for 12-month (OR 8.51, 95% CI 3.35-21.63) and 24-month (OR 6.04, 95% CI 2.06-17.70) lead time before diagnosis. No associations for other medications were found. This study underscores the need to examine potential carcinogenic effects of the medication classes highlighted and of the indication of medication use. Despite possible reverse causality, increased CBT surveillance for children with epilepsy might be warranted.