Risk Of Brain Tumors Research Articles

Association between Airport-Related Ultrafine Particles and Risk of Malignant Brain Cancer: A Multiethnic Cohort Study

Ultrafine particles (UFP; diameter less than or equal to 100 nm) may reach the brain via systemic circulation or the olfactory tract and have been implicated in the risk of brain tumors. The effects of airport-related UFP on the risk of brain tumors are not known. Here we determined the association between airport-related UFP and risk of incident malignant brain cancer (n = 155) and meningioma (n = 420) diagnosed during 16.4 years of follow-up among 75,936 men and women residing in Los Angeles County from the Multiethnic Cohort study. UFP exposure from aircrafts was estimated for participants who lived within a 53 km × 43 km grid area around the Los Angeles International Airport (LAX) from date of cohort entry (1993-1996) through December 31, 2013. Cox proportional hazards models were used to estimate the effects of time-varying, airport-related UFP exposure on risk of malignant brain cancer and meningioma, adjusting for sex, race/ethnicity, education, and neighborhood socioeconomic status. Malignant brain cancer risk in all subjects combined increased 12% [95% confidence interval (CI), 0.98-1.27] per interquartile range (IQR) of airport-related UFP exposure (∼6,700 particles/cm3) for subjects with any address in the grid area surrounding the LAX airport. In race/ethnicity-stratified analyses, African Americans, the subgroup who had the highest exposure, showed a HR of 1.32 (95% CI, 1.07-1.64) for malignant brain cancer per IQR in UFP exposure. UFP exposure was not related to risk of meningioma overall or by race/ethnicity. These results support the hypothesis that airport-related UFP exposure may be a risk factor for malignant brain cancers. SIGNIFICANCE: Malignant brain cancer risk increases with airport-related UFP exposure, particularly among African Americans, suggesting UFP exposure may be a modifiable risk factor for malignant brain cancer.

Constitutional mismatch repair deficiency is a childhood cancer predisposition syndrome associated with an increased risk of high grade paediatric brain tumours: report of 3 cases and review of the literature

Background: Constitutional mismatch repair deficiency syndrome (CMMRD) represents a biallelic (homozygous or compound heterozygous) mutation in one of the mismatch repair genes (MLH1, MSH2, MSH6 or PMS2), resulting in a recessively inherited childhood cancer predisposition syndrome. A broad range of tumours in infants and children have been described in the CMMRD spectrum, most commonly brain tumours, intestinal tumours, and haematological malignancies. This contrasts with the monoallelic mismatch repair defects (MMR) of Lynch syndrome, in which there is an increased risk of development of malignancies in particular involving the gastrointestinal and genitourinary tract, with onset in adulthood. Phenotypic features of CMMRD overlap with neurofibromatosis, with café-au-lait macules a common finding in this cohort. Aims: To highlight an increasingly recognised childhood cancer predisposition syndrome, and the importance of identification of these cases given significant implications for family counselling. There is an increased cancer risk in siblings, as well as for the parents, who may not yet be aware of their own associated monoallelic MMR defect (Lynch syndrome). Methods: We present three cases of childhood primary brain tumours that were subsequently confirmed in the setting of CMMRD. The histological, immunohistochemical and genetic findings of these cases are discussed, with focus on diagnostic pathologic features that suggest an underlying CMMRD. Results and conclusions: Three high grade brain tumours described include two high grade gliomas (a glioblastoma multiforme and a high grade diffuse intrinsic pontine glioma, H3K27M negative), and a medulloblastoma. These examples all showed complete absence of PMS2 staining on immunohistochemistry in both tumour cells and normal ‘internal control’ tissues of the patient, correlating with biallelic loss of gene function. Review of the literature shows brain tumours as the most frequent presentation in children with CMMRD, with an increased risk of gastrointestinal tumours (including colonic carcinoma) and haematological malignancies also reported.

Polymorphism in miRNA target sites of CEP-63 and CEP-152 ring complex influences expression of CEP genes and favors tumorigenesis in glioma.

Purpose: The present study was designed to screen the genetic polymorphisms and expression profiling of CEP-152 and CEP-63 genes in brain tumor patients. Methods: The amplification refractory mutation system PCR technique (ARMS-PCR)was used for mutation analysis using 300 blood samples of brain tumor patients and 300 overtly healthy controls. For expression analysis, 150 brain tumor tissue samples along with adjacent uninvolved/normal tissues (controls) were collected. Results: A significantly higher frequency of the mutant genotype of the CEP-152 single nucleotide polymorphism (rs2169757) and CEP-63 single nucleotide polymorphisms (rs9809619 and rs13060247) was observed in patients versus overtly healthy controls. The authors' results showed highly significant deregulation of CEP-152 (p<0.0001) and CEP-63 (p<0.0001) in glioma/meningioma tumor tissues versus adjacent normal tissue. Conclusion: The present study showed that variations in CEP-152 and CEP-63 genes were associated with an increased risk of brain tumor.

Exposure to drinking water trihalomethanes and nitrate and the risk of brain tumours in young people

Brain tumours (BTs) are one of the most frequent tumour types in young people. We explored the association between tap water, exposure to trihalomethanes (THM) and nitrate and neuroepithelial BT risk in young people. Analysis of tap water consumption were based on 321 cases and 919 appendicitis controls (10–24 years old) from 6 of the 14 participating countries in the international MOBI-Kids case-control study (2010–2016). Available historical residential tap water concentrations of THMs and nitrate, available from 3 countries for 86 cases and 352 controls and 85 cases and 343 for nitrate, respectively, were modelled and combined with the study subjects’ personal consumption patterns to estimate ingestion and residential exposure levels in the study population (both pre- and postnatal). The mean age of participants was 16.6 years old and 56% were male. The highest levels and widest ranges for THMs were found in Spain (residential and ingested) and Italy and in Korea for nitrate. There was no association between BT and the amount of tap water consumed and the showering/bathing frequency. Odds Ratios (ORs) for BT in relation to both pre- and postnatal residential and ingestion levels of THMs were systematically below 1 (OR = 0.37 (0.08–1.73)) for postnatal average residential THMs higher than 66 μg/L. For nitrate, all ORs were above 1 (OR = 1.80 (0.91–3.55)) for postnatal average residential nitrate levels higher than 8.5 mg/L, with a suggestion of a trend of increased risk of neuroepithelial BTs with increasing residential nitrate levels in tap water, which appeared stronger in early in life. This, to our knowledge, is the first study on this topic in young people. Further research is required to clarify the observed associations.

Rare germline variants in the E-cadherin gene CDH1 are associated with the risk of brain tumors of neuroepithelial and epithelial origin

The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced β-catenin binding resulting in increased cytosolic and nuclear β-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/β-catenin signaling.

A cohort study on adult hematological malignancies and brain tumors in relation to magnetic fields from indoor transformer stations.

Extremely low frequency (ELF) magnetic fields (MF) have been classified as possibly carcinogenic. This classification was mainly based on studies indicating increased risk of leukemia in children living near power lines. Increased risks of adult hematological malignancies and brain tumors have also been reported, but the results are mixed. We assessed incidence of adult hematological malignancies and brain tumors associated with residential MF exposure. All cohort members had lived in buildings with indoor transformer stations (TS). MF exposure was assessed based on apartment location. Out of the 256,372 individuals, 9,636 (165,000 person-years of follow-up) living in apartments next to TSs were considered as exposed. Associations between MF exposure and neoplasms were examined using Cox proportional hazard models. The hazard ratio (HR) for MF exposure≥1 month was below one for most hematological neoplasms (HR for any hematological neoplasm: 0.75; 95% CI: 0.54-1.03), and decreased with increasing duration of exposure (HR for exposure≥10 years: 0.47; 95% CI: 0.22-0.99). However, the HR for acute lymphocytic leukemia (ALL) was 2.86 (95% CI: 1.00-8.15), based on 4 exposed cases; the risk increased with duration of exposure (HR for exposure ≥3 years: 3.61; 95% CI: 1.05-12.4) and was particularly associated with childhood exposure (2 exposed cases, HR for exposure during the first two years of life: 11.5; 95% CI: 1.92-68.9). The HR for meningioma was 0.46 (95% CI: 0.19-1.11), with no evidence of exposure-response gradient with increasing duration of exposure. The HR for glioma was 1.47 (95% CI: 0.84-2.57). The hypothesis of a positive association between ELF MFs and adult hematological malignancies was supported only for ALL. The results suggested decreased rather than increased risk of most hematological neoplasms.

Risk of Leukemia and Brain Tumors in Children Exposed to Pesticide Residual in Households and Approaches to Reduce its Side Effect

Context: Using various pesticides to control pests and vectors of diseases has a long history in households worldwide. However, most pesticides are considered toxic to and harmful to the environment. Evidence Acquisition: Electronic databases such as Google Scholar, PubMed, and Scopus were searched using the following search terms: “children”, “pesticide residues”, “risks”, “leukemia”, and “brain neoplasms”. This review was designed to identify the relevant electronic studies published from January 2000 to February 2020. Results: Children are more susceptible to pesticides because of their underdeveloped metabolic processes and disability to detoxify chemicals. Over 30% of the children’s diseases are due to environmental factors, including pesticides. The possibility of children’s pesticide exposure inside of urban houses is more than outside. In general, children can be exposed to pesticides in two ways: Direct and indirect contact. Direct contact refers to hand-to-mouth behavior in daily plays that absorbs household pesticides. Indirect contact refers to exposure via their parents’ work in hazardous environments and during pregnancy. There is a significant association between pesticide exposure via households and some cancers in children, such as leukemia and brain tumors. Conclusions: Due to the positive association between pesticide residues in households and the risk of cancers in children, public health policies must be adopted to minimize children’s exposure to pesticides in the urban household.

Projected future risk of leukemia and brain tumors from unnecessary brain CT scans: a multi-center study in Iran

Introduction: Computer Tomography (CT) scans can deliver a relatively high radiation dose to the patient, therefore radiation protection for this modality is paramount. The present study determined the frequency of no abnormality detected (NAD) brain CT scans and probability of cancer induction in different age groups and genders. Methods: In this study, brain CT reports were used to identify any findings as abnormality detected (AD) and others as NAD. Then probability of future leukemia and brain cancer was estimated for different age and gender groups. Results: On average, in 65% of the cases the results were NAD (56% and 76% among males and females, respectively). Among children, 79% of the reports were NAD. The total number of projected brain cancers was 1.8 and 1.3 for males and females, respectively. The number of projected leukemia cases was 0.75 and 0.7 for males and females, respectively. For pediatric patients, brain CT scans can lead to leukemia cases about 4.5 times more often than adults. Conclusion: Brain CT scans can lead to additional cases of brain cancer and leukemia. A significant fraction of brain CTs were NAD (non-pathologic) and could practically be replaced by other radiation-free imaging modalities, especially in pediatric and young patients.

Influence of growth hormone therapy on the occurrence of a second neoplasm in survivors of childhood cancer.

Growth hormone (GH) deficiency is a common late effect of cranial irradiation. However, concerns have been raised that GH treatment might lead to an increased risk of a second neoplasm (SN). To study the impact of GH treatment on the risk of SN in a French cohort of survivors of childhood cancer (CCS) treated before 1986. Cohort study and nested case-control study. Of the 2852 survivors, with a median follow-up of 26 years, 196 had received GH therapy (median delay from cancer diagnosis: 5.5 years). Occurrence of SN. In total, 374 survivors developed a SN, including 40 who had received GH therapy. In a multivariate analysis, GH treatment did not increase the risk of secondary non-meningioma brain tumors (RR: 0.6, 95% CI: 0.2-1.5, P = 0.3), secondary non-brain cancer (RR: 0.7, 95% CI: 0.4-1.2, P = 0.2), or meningioma (RR: 1.9, 95% CI: 0.9-4, P = 0.09). Nevertheless, we observed a slight non-significant increase in the risk of meningioma with GH duration: 1.6-fold (95% CI: 1.2-3.0) after an exposure of less than 4 years vs 2.3-fold (95% CI: 0.9-5.6) after a longer exposure (P for trend = 0.07) confirmed by the results of a case-control study. This study confirms the overall safety of GH use in survivors of childhood cancer, which does not increase the risk of a SN. The slight excess in the risk of meningioma in patients with long-term GH treatment is non-significant and could be due to difficulties in adjustment on cranial radiation volume/dose and/or undiagnosed meningioma predisposing conditions.

Computed tomography of the head and the risk of brain tumours during childhood and adolescence: results from a case–control study in Japan

To clarify whether medical radiation exposure, especially from head computed tomography (CT), increases the risk of brain tumours in young patients in Japan, which ranks the second highest in the world in the number of paediatric CT examinations following the US. From 2011 to 2015, we performed a case–control study of 120 brain tumour patients and 360 appendicitis patients as controls. Reasons, the number of brain and head CT scans date were available from interviews. A cumulative radiation dose to the brain was calculated as a sum of doses received from head CT scans and from conventional x-rays and estimated using a reference table derived from a literature review of published studies. We performed conditional logistic regression to assess the risk of brain tumours from brain and head CT, and from conventional head x-ray procedures. The case group received on average 1.8 CTs to the brain area and 2.2 CTs to the whole head, with a mean estimated brain dose of 32 ± 13 mGy. The odds ratio for developing a brain tumour from having a brain CT was 0.93 (95% confidence interval: 0.38–1.82). This was hardly altered when adjusting for parental educational history and for other diseases (history of neurological disease and attention-deficit disorder/attention-deficit hyperactivity disorder). Neither whole head CT nor cumulative brain dose to the brain increased the risk of glioma or of all brain tumours. Although this study conducted in Japan, where ranks second in the number of CT scans conducted in the world, did not show an increased risk of brain tumours related to CT scans, it should be taken with caution due to a case–control study with limited sample size.

Primary CNS tumors in adults and environmental factors: an update

The incidence of adult primary brain tumors is increasing in some European countries. High-dose ionizing irradiation, rare genetic syndromes, and genetic predisposition in 5 % of families are a few established environmental risk factors for brain tumor. Mobile phone use that causes near brain exposure to radiofrequency electromagnetic waves and thus creates risks of CNS tumors has been the focus of many studies. Nine meta-analyses were available on this subject. The Interphone multi-center case-control study is the largest one to date; it included 2.708 glioma and 2.409 meningioma cases and matched controls in 13 countries. Studies exploring metals (cadmium, lead), pesticides, outdoor pollution, virus, and risk of glioma created by exposure to them were reviewed. Interphone study did not show increased risk of glioma or meningioma in mobile-phone users. One recent meta-analysis in 2017 found that prolonged exposure i.e.,&gt; 10 years of all phone types was associated with increased risk of ipsilateral CNS tumor locations. In another meta-analysis, long-term use of mobile-phones was found to be a risk factor for low-grade glioma. In case of all durations regarding mobile phone use and both sides of the head, the results of pooling data were more discordant. A large prospective study in 2014 showed that long term use vs never use increased risks of acoustic neurinoma (10+ years: RR = 2.46, 95 % CI = 1.07–5.64, P = 0.03), but not of glioma or meningioma. Studies of other risk factors showed no/weak/contradictory association with brain tumor risk. In the absence of robust and consistent evidence, a causal relation between radiofrequency exposure and CNS tumors was not found. Large prospective studies of this kind regarding a disease with low incidence require a high number of participants and a long follow-up period.

Первичные опухоли центральной нервной системы у взрослого населения и факторы окружающей среды: обновленный обзор существующих публикаций

The incidence of adult primary brain tumors is increasing in some European countries. High-dose ionizing irradiation, rare genetic syndromes, and genetic predisposition in 5 % of families are a few established environmental risk factors for brain tumor. Mobile phone use that causes near brain exposure to radiofrequency electromagnetic waves and thus creates risks of CNS tumors has been the focus of many studies. Nine meta-analyses were available on this subject. The Interphone multi-center case-control study is the largest one to date; it included 2.708 glioma and 2.409 meningioma cases and matched controls in 13 countries. Studies exploring metals (cadmium, lead), pesticides, outdoor pollution, virus, and risk of glioma created by exposure to them were reviewed. Interphone study did not show increased risk of glioma or meningioma in mobile-phone users. One recent meta-analysis in 2017 found that prolonged exposure i.e.,&gt; 10 years of all phone types was associated with increased risk of ipsilateral CNS tumor locations. In another meta-analysis, long-term use of mobile-phones was found to be a risk factor for low-grade glioma. In case of all durations regarding mobile phone use and both sides of the head, the results of pooling data were more discordant. A large prospective study in 2014 showed that long term use vs never use increased risks of acoustic neurinoma (10+ years: RR = 2.46, 95 % CI = 1.07–5.64, P = 0.03), but not of glioma or meningioma. Studies of other risk factors showed no/weak/contradictory association with brain tumor risk. In the absence of robust and consistent evidence, a causal relation between radiofrequency exposure and CNS tumors was not found. Large prospective studies of this kind regarding a disease with low incidence require a high number of participants and a long follow-up period.

Components of particulate matter air-pollution and brain tumors

BackgroundAir pollution is an established carcinogen. Evidence for an association with brain tumors is, however, inconclusive. We investigated if individual particulate matter constituents were associated with brain tumor risk. MethodsFrom comprehensive national registers, we identified all (n = 12 928) brain tumor cases, diagnosed in Denmark in the period 1989–2014, and selected 22 961 controls, matched on age, sex and year of birth. We established address histories and estimated 10-year mean residential outdoor concentrations of particulate matter < 2.5 µm, primarily emitted black carbon (BC) and organic carbon (OC), and combined carbon (OC/BC), as well as secondary inorganic and organic PM air pollutants from a detailed dispersion model. We used conditional logistic regression to calculate odds ratios (OR) per inter quartile range (IQR) exposure. We adjusted for income, marital and employment status as well as area-level socio-demographic characteristics. ResultsTotal tumors of the brain were associated with OC/BC (OR: 1.053, 95%CI: 1.005–1.103, per IQR). The data suggested strongest associations for malignant tumors with ORs per IQR for OC/BC, BC and OC of 1.063 (95% CI: 1.007–1.123), 1.036 (95% CI: 1.006–1.067) and 1.030 (95%CI: 0.979–1.085), respectively. The results did not indicate adverse effects of other PM components. ConclusionsThis large, population based study showed associations between primary emitted carbonaceous particles and risk for malignant brain tumors. As the first of its kind, this study needs replication.

Body mass index and height in relation to brain tumor risk in a Japanese population

PurposeAlthough height and body mass index (BMI) are reported to be positively associated with several common cancers, evidence regarding their association with brain tumor risk remains sparse, particularly in Asian populations. In this study, we analyzed the association between height and BMI and brain tumor risk in a Japanese population using a large population-based prospective cohort study. MethodsA total of 102,925 participants (48,213 men and 54,712 women) enrolled in the Japan Public Health Center–based Prospective Study were followed from baseline, namely 1990 for cohort I and 1993 for cohort II, until 2012. Information on participants’ dietary and lifestyle habits, including height and body weight, was collected through survey questionnaires administered at baseline. We used the Cox proportional hazards regression model to estimate hazard ratios and 95% confidence intervals (CIs) for brain tumor incidence, with adjustment for potential confounding variables. ResultsDuring an average follow-up of 18.1 years, 157 (70 men and 87 women) cases of brain tumor were newly diagnosed. BMI showed a statistically insignificant positive association with the risk of brain tumor. In addition, statistically significant positive trends were seen for men and meningioma, with multivariable-adjusted hazard ratios for a BMI of 27.5 to less than 40 versus 18.5 to less than 23 kg per m2 of 2.14 (95% CI = 0.99–4.59) (P = 0.03) and 1.98 (95% CI = 0.84–4.67) (P = 0.046), respectively. In contrast, height showed no clear association with brain tumor risk, overall or in subgroup analysis. ConclusionsCompared with a BMI of 18 to less than 23.5 kg per m2, a higher BMI was associated with higher risk of brain tumor, particularly in men and with meningioma.

Abstract 5779: The association of instrument assisted deliveries and the development of childhood brain tumors: A matched case control study

Abstract Background: Pediatric brain tumors are the second most common type of childhood cancer and have the highest mortality rate among all pediatric cancer types. New information on potentially preventative measures would be of great value. Previous studies have suggested that instrument-assisted delivery (forceps and vacuum) may be associated with an increased risk for childhood brain tumors. The goal of this study was to determine if there was an association of exposure to instrument-assisted deliveries with childhood brain tumors in Denmark. We additionally examined risk with emergency or planned cesarean section. Methods: This was a matched case-control study with childhood brain tumor cases in Denmark diagnosed from 1978-2013. Cases were identified from the Danish Cancer Registry. Birth outcomes, maternal procedures and covariates were obtained from the Danish Medical Births Register and the nationwide Hospital Register. A total of 3,698 brain tumor cases were recruited and 25 controls were matched to each case based on child's sex and birth year (N=89,554). We used conditional logistic regression to determine associations of delivery instruments types with various childhood brain tumors. Results: Compared to children birthed by spontaneous vaginal delivery, children who later developed ependymomas (N=136) had a greater likelihood of having been delivered by vacuum assisted deliveries (OR=1.69, 95% CI 1.01-2.83). An overall increased risk for cesarean section with any CNS tumor (OR= 1.20, 95% CI 1.06-1.36) dropped to 1.10 when we limited the age range to 4 or older (N=1,087). This suggests no clear increased risk for cancer with cesarean section, as there is a possibility that the CNS tumor was present before birth and influenced a larger head size, thus requiring a cesarean section. Planned cesarean and emergency cesarean section were not related to risk increases. While the use of forceps was rare in this population (1.2% in controls), we could not confirm previously reported associations with astrocytoma (OR=0.84), though there was a weak increase for ependymoma with wide confidence intervals (OR=2.69, 95% CI 0.77, 9.38). Conclusions: Based on objective data, the findings in our study suggest that there might be an association between vacuum assisted deliveries and ependymomas. Our data did not support a strong association of childhood brain tumors with cesarean sections. Citation Format: Karen Yeh, Johnni Hansen, Julia E. Heck. The association of instrument assisted deliveries and the development of childhood brain tumors: A matched case control study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5779.

Occupational exposure to unintentionally emitted nanoscale particles and risk of cancer: From lung to central nervous system - Results from three French case-control studies

ObjectivesNanoscale particles (1–100 nm) can be of natural origin, and either intentionally or unintentionally produced by human activities. Toxicological data have suggested a possible carcinogenic effect of such particles. The aim of this study was to estimate the association between occupational exposure to nanoscale particles and risk of lung cancer, pleural mesothelioma and brain tumors in adults. MethodsThree French population-based case-control studies were analyzed: 1) the ICARE study including 2029 lung cancer cases and 2591 controls; 2) the PNSM study including 371 pleural mesothelioma cases and 730 controls and 3) the CERENAT study including 257 brain tumor cases and 511 controls. Occupational exposure to unintentionally emitted nanoscale particles (UNPs) was retrospectively assessed by a job exposure matrix providing a probability and a frequency of exposure. ResultsIn adjusted analyses among men, significant associations between occupational exposure to UNPs and lung cancer (OR = 1.51; 95% CI: 1.22–1.86 and brain tumors (OR = 1.69; 95% CI: 1.17–2.44) were observed. No increased OR was observed for pleural mesothelioma (OR = 0.78; 95% CI: 0.46–1.33). ConclusionThis is the first study showing positive associations between occupational exposure to UNPs and increased risk of lung cancer and brain tumors. These preliminary results should encourage further epidemiological research.

Clinical indications for the use of computed tomography in children who underwent frequent computed tomography: a near-13-year follow-up retrospective study at a single institution in Japan.

Recent studies suggest a causal link of childhood leukemia and brain tumor with repeated computed tomography (CT) scans. The reasons why frequent CT scans are taken in a specific child remain unclear. The present study aimed to clarify the medical reasons why frequent CT examinations in children, and the characteristics of the diseases of those children that required multiple CT scans. A long-term follow-up retrospective study was conducted over a 12.75-year period at a single institution. Radiological reports were investigated that contained the indications for the CT scans. The clinical indications were classified for the examination of children under 16 years of age who underwent more than three CT scans into trauma, tumor, inflammation, and others. This study showed that 8.5% of CT examinations were done three times or more. The numbers of patients by indication were 23.3% for trauma, 5.3% for hydrocephalus, and 2.3% for appendicitis. The frequencies of trauma and inflammation decreased rapidly with an increasing number of CT scans. In particular, hydrocephalus brought high frequency more than ten scans. Regarding the frequencies of clinical indications by age groups, there was a significant difference (p<0.05). The near-13-year follow-up study indicated the main clinical indications for frequent CT scans in children were trauma and hydrocephalus. Multiple follow-up CT scans in children with hydrocephalus would be traded off against the resultant increase in brain tumor risk associated with CT exposure.

Occupational Lead Exposure and Brain Tumors: Systematic Review and Meta-Analysis

(1) Background: Due to inconsistencies in epidemiological findings, there has been uncertainty regarding the association of lead compounds with brain tumors. We performed a meta-analysis of published case-control and cohort studies exploring lead compound exposure and brain tumor risk. (2) Methods: We searched PubMed, Embase®, and Cochrane to find eligible studies. Eighteen studies were selected for assessment of occupational exposure to lead compound and brain tumor. Pooled estimates of odds ratios (ORs) were obtained using random effects models. We assessed the differences through subgroup analysis according to tumor type, study design, measurements of exposure, and tumor outcome. Statistical tests for publication bias, heterogeneity, and sensitivity analysis were applied. (3) Results: Our systematic review and meta-analysis showed a not significant association with lead exposure and risk of benign and malignant brain tumors (pooled OR = 1.11, 95% Confidence Interval (CI): 0.95–1.29). Including only malignant brain tumors, the risk of brain tumor was significantly increased (pooled OR = 1.13, 95% CI: 1.04–1.24). (4) Conclusions: This meta-analysis provides suggestive evidence for an association between lead compound exposure and brain tumor. In future studies, it will be necessary to identify the effect of lead compounds according to the types of brain tumor.

Genetic and expression variations of cell cycle pathway genes in brain tumor patients.

The present study was designed to determine the association between the genetic polymorphisms/expression variations of RB1 and CCND1 genes and brain tumor risk. For this purpose, 250 blood samples of brain tumor patients along with 250 controls (cohort I) and 96 brain tumor tissues (cohort II) with adjacent control section were collected. Mutation analysis of RB1 (rs137853294, rs121913300) and CCND1 (rs614367, rs498136) genes was performed using ARMS-PCR followed by sequencing, and expression analysis was performed using real-time PCR and immunohistochemistry. The results showed homozygous mutant genotype of RB1 gene polymorphism, rs121913300 (P=0.003) and CCND1 gene polymorphism rs614367 (P=0.01) were associated significantly with brain tumor risk. Moreover, significant down-regulation of RB1 (P=0.005) and up-regulation of CCND1 (P=0.0001) gene was observed in brain tumor sections vs controls. Spearman correlation showed significant negative correlation between RB1 vs proliferation marker, Ki-67 (r = −0.291*, P<0.05) in brain tumors. Expression levels of selected genes were also assessed at protein level using immunohistochemical analysis (IHC) and signification down-regulation of RB1 (P=0.0001) and up-regulation of CCND1 (P=0.0001) was observed in brain tumor compared with control sections. In conclusion, it is suggested that polymorphisms/expression variations of RB1 and CCND1 genes may be associated with increased risk of brain tumor.

Maternal Occupational Exposures and Adverse Pregnancy Outcomes: An Overview of Meta- Analysis

Background: Working pregnant women are exposed to numerous occupational exposures, some of which may adversely affect their reproductive health. We aimed to review the effects of maternal occupational exposures and adverse effects on the infants. Materials and Methods: In this overview, searches were done on the online databases of Scopus, EMBASE, Cochrane, Web of Science and Medline; with no language or time restrictions (up to December 2019) to find studies that assess the relationship between maternal occupational exposures and adverse pregnancy outcomes. Two independent researchers performed the search process and a supervisor judged any disagreement in this regard. Results: Women occupationally exposed to anaesthetic gases had increased risk of spontaneous abortion. Second study reported specific birth defects including limb defects, cleft lip and cleft palate neural tube defects, urinary tract defects and congenital heart defects. In the third study, increased risk of childhood brain tumors was seen following maternal occupational exposures to chlorinated solvents. In the fourth study, a positive relationship between maternal exposures to ambient air pollution with autism spectrum disorder. In the fifth study, a significant relationship between anesthetic gases and congenital malformation, chemotherapy agent and spontaneous abortion and between shift work and spontaneous abortion. In the sixth study, exposure to endocrine-disrupting chemicals, group at work showed an increased risk of LBW with the odds ratio of 1.25, 95% CI: 1.04, 1.49. In the seventh study, exposure to ambient air pollution increases the risk of stillbirth. In eight, a statistically significant association between childhood leukemia and parental occupation. Conclusion: Maternal occupational exposures can be can be leading risk factors for many adverse pregnancy outcomes and birth defects.