Risk Of Central Nervous System Tumors Research Articles

The regulatory role and clinical application prospects of circRNA in the occurrence and development of CNS tumors.

Central nervous system (CNS) tumors originate from the spinal cord or brain. The study showed that even with aggressive treatment, malignant CNS tumors have high mortality rates. However, CNS tumor risk factors and molecular mechanisms have not been verified. Due to the reasons mentioned above, diagnosis and treatment of CNS tumors in clinical practice are currently fraught with difficulties. Circular RNAs (circRNAs), single-stranded ncRNAs with covalently closed continuous structures, are essential to CNS tumor development. Growing evidence has proved the numeral critical biological functions of circRNAs for disease progression: sponging to miRNAs, regulating gene transcription and splicing, interacting with proteins, encoding proteins/peptides, and expressing in exosomes. This review aims to summarize current progress regarding the molecular mechanism of circRNA in CNS tumors and to explore the possibilities of clinical application based on circRNA in CNS tumors. We have summarized studies of circRNA in CNS tumors in Pubmed. This review summarized their connection with CNS tumors and their functions, biogenesis, and biological properties. Furthermore, we introduced current advances in clinical RNA-related technologies. Then we discussed the diagnostic and therapeutic potential (especially for immunotherapy, chemotherapy, and radiotherapy) of circRNA in CNS tumors in the context of the recent advanced research and application of RNA in clinics. CircRNA are increasingly proven to participate in decveloping CNS tumors. An in-depth study of the causal mechanisms of circRNAs in CNS tomor progression will ultimately advance their implementation in the clinic and developing new strategies for preventing and treating CNS tumors.

Early-onset grade 2-3 diffuse gliomas and schwannomas increase the risk of central nervous system tumors among the patients' relatives.

Central nervous system (CNS) tumors are a heterogeneous group of tumors that include several aggressive malignancies with a high mortality rate. This study aimed to evaluate the familial relative risk of CNS tumors in family members of early-onset index cases (probands) in and between diffuse glioma, non-diffuse glioma, meningioma, and other CNS tumors. We retrieved tumor data from the Finnish cancer registry and familial relationships data from the population information system. We ascertained 5408 probands diagnosed with primary CNS tumors (age ≤40 years) between 1970 and 2012 in Finland. We report the standardized incidence ratios as a measure of familial aggregation using Poisson regression. The risk of early-onset diffuse glioma increased among siblings of probands with the same tumor [SIR 3.85, 95% confidence interval (CI): 1.66-7.59], with association mainly returning to grade 2-3 diffuse gliomas. Early-onset other CNS tumors were associated with an increased risk of other CNS tumors, early-onset meningioma, and late-onset diffuse glioma in 1st-degree relatives. The elevated risk of other CNS tumors was largely caused by schwannomas (SIR 59.44, 95% CI: 27.18-112.84 for 1st-degree relatives) and associated with neurofibromatosis. No tumor syndrome was associated with an increased risk of diffuse gliomas. The early onset of grade 2-3 diffuse gliomas is associated with an increased risk of similar tumor entities. Early-onset schwannomas dramatically increase CNS tumor risk with a broader tumor-type profile. In future studies, it would be important to identify the underlying shared hereditary factors that contribute to the development of familial diffuse gliomas.

Food processing and risk of central nervous system tumours: A preliminary case–control analysis from the MEditerranean DIet in relation to CancEr of brAin (MEDICEA) study

The relationship between diet and central nervous system (CNS) tumours was almost exclusively focused on food composition. We evaluated the relationship of different degrees of food processing with risk of CNS tumours. The study sample included 44 CNS tumours cases (20 non-malignant and 24 malignant) recruited from the Neurosurgery Department at the IRCCS Neuromed (Italy), and 88 controls matched 1:2 for sex and age± 10 years, identified from the Moli-sani Study. Dietary intake was assessed using a 188-item FFQ. Food items were grouped according to the NOVA classification on the basis of processing as: (1) unprocessed/minimally processed foods; (2) processed culinary ingredients; (3) processed foods; and (4) ultra-processed food (UPF). Conditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence intervals (95%CI) of dietary contributions from each NOVA group (as weight ratio on the total food eaten) and adjusting for potential confounders. In a multivariable conditional to match logistic regression analysis also controlled for overall diet quality, 1% increment in UPF intake was associated with higher odds of all CNS tumours (OR=1.06; 1.01-1.13), particularly of malignant CNS tumours (OR=1.11; 1.02-1.22), while no association with non-malignant CNS tumours was found (OR=1.06; 0.99-1.15). In contrast, only processed food was inversely associated with risk of both CNS tumours overall (OR=0.94; 0.90-0.98) and of malignant CNS tumours (OR=0.90; 0.83-0.96). Increasing UPF intake was associated with higher risk of CNS tumours, especially malignant ones, independently of the overall diet quality, while only processed food (but not UPF) was inversely related to the risk of this disease.

Ionizing radiation exposure during adulthood and risk of developing central nervous system tumors: systematic review and meta-analysis

Many studies on ionizing radiation (IR) exposure during childhood have shown deleterious effects on the central nervous system (CNS), however results regarding adult exposure are inconsistent, and no systematic reviews have been performed. The objectives are to synthesize the findings and draw evidence-based conclusions from epidemiological studies on the risk of benign and malignant brain and CNS tumors in humans exposed to low-to-moderate doses (< 0.5 Gy) of IR during adulthood/young adulthood. A systematic literature search of four electronic databases, supplemented by a hand search, was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled excess relative risk (ERRpooled) was estimated using a random effect model. Eighteen publications were included in the systematic review and twelve out of them were included in a meta-analysis. The following IR sources were considered: atomic bombs, occupational, and environmental exposures. No significant dose-risk association was found for brain/CNS tumors (ERRpooled at 100 mGy = − 0.01; 95% CI: − 0.05, 0.04). Our systematic review and meta-analysis did not show any association between exposure to low-to-moderate doses of IR and risk of CNS tumors. Further studies with histological information and precise dose assessment are needed.

O-083 Tumors of the central nervous system among women treated with fertility drugs: a population-based cohort study

Abstract Study question Is the use of fertility drugs among infertile women associated with tumors of the central nervous system (CNS)? Summary answer The use of most specific types of fertility drugs is not associated with an increased risk of CNS tumors overall. What is known already Few previous studies have investigated the association between fertility drugs and CNS tumors. Studies have reported inconsistent results regarding the risk of CNS tumors associated with assisted reproductive technologies such as in vitro fertilization (IVF). No studies have reported the risk associated with various specific fertility drugs. Study design, size, duration Retrospective population-based cohort study of all women included in the Danish Infertility Cohort. The study cohort consisted of 148 016 infertile women after exclusion of women who emigrated, died, were diagnosed with cancer before infertility diagnosis, and women for whom information on level of education was missing. The cohort was linked to various national health- and civil registers to study all 20- to 45-year old infertile women in Denmark during 1995-2017. Participants/materials, setting, methods The study cohort was linked to various national health and population registers to obtain information on fertility drugs (clomiphene citrate, gonadotropins, human chorionic gonadotropin, gonadotropin-releasing hormone receptor modulators and progesterone), CNS tumors, relevant covariates and vital and emigration status. Cox proportional hazard regression models were used to calculate hazard ratios and 95% confidence intervals for CNS tumors overall and for gliomas, meningiomas and diverse benign tumors of the brain and other parts of the CNS. Main results and the role of chance During a median 11.3 years of follow-up, 328 women were diagnosed with a CNS tumor. No marked associations were observed between use of most types of fertility drugs (clomiphene citrate, gonadotropins, gonadotropin releasing hormone receptor modulators and progesterone) and CNS tumors. However, ever use of human chorionic gonadotropin was associated with an increased rate of gliomas (HR 2.13 95% CI 0.90-5.01) but a decreased rate of meningiomas (HR 0.49 95% CI 0.28-0.87). No clear associations with CNS tumors were observed according to time since first use or cumulative dose for any specific fertility drugs. Additional studies with longer follow-up are necessary to support these findings. Limitations, reasons for caution The median age at end of follow-up (43.5 years) was lower than the median age for CNS tumors diagnosis (60 years). Information on estrogen use, treatment regimens and number of cycles is only partly available in the registers and these were not included in this study. Wider implications of the findings This study presents reassuring results regarding the risk of tumors of the CNS among women treated with fertility drugs. Our study is only generalizable to premenopausal women, and the risk for postmenopausal women remains to be assessed. Trial registration number not applicable

Association Between Maternal Hormonal Contraception Use and Central Nervous System Tumors in Children

The incidence of central nervous system (CNS) tumors in children appears to be increasing, yet few risk factors are established. There is limited information regarding whether maternal hormonal contraception use increases this risk. To examine the association between maternal hormonal contraception use and CNS tumors in children (<20 years). In this nationwide cohort study based on population-based registry data, 1 185 063 children born in Denmark between January 1, 1996, and December 31, 2014, were followed up for a diagnosis of a CNS tumor (final follow-up on December 31, 2018). Maternal hormonal contraception use was analyzed according to any use, regimen (combined/progestin only), and route of administration (oral/nonoral), categorized as recent use (≤3 months before start and during pregnancy), previous use (>3 months before start of pregnancy), and no use. For injections, implants, and intrauterine devices that are used for a different time period, the categorization was appropriately altered. Hazard ratio (HR) and incidence rate difference (IRD) of CNS tumors diagnosed at younger than 20 years. After 15 335 990 person-years of follow-up (mean follow-up, 12.9 years), 725 children were diagnosed with a CNS tumor. The mean age at diagnosis was 7 years, and 342 (47.2%) of the diagnosed children were female. The adjusted incidence rate of CNS tumors per 100 000 person-years was 5.0 for children born to mothers with recent hormonal contraception use (n = 136 022), 4.5 for children born to mothers with previous use (n = 778 843), and 5.3 for children born to mothers with no use (n = 270 198). The corresponding HRs were 0.95 ([95% CI, 0.74-1.23]; 84 children with CNS tumors; IRD, -0.3 [95% CI, -1.6 to 1.0]) for recent use and 0.86 ([95% CI, 0.72-1.02]; 421 children with CNS tumors; IRD, -0.8 [95% CI, -1.7 to 0.0]) for previous use, compared with no use. No statistically significant associations were found for recent or previous use of oral combined, nonoral combined, oral progestin only, or nonoral products compared with no use of hormonal contraception. Among Danish children, there was no statistically significant association between any maternal hormonal contraception use and CNS tumor risk.

Associations between LMO1 gene polymorphisms and central nervous system tumor susceptibility.

ABSTRACTImportanceLIM domain only 1 (LMO1) gene polymorphisms were previously found to be implicated in the risk of several cancers. No available studies were performed regarding the predisposing effect of LMO1 gene single nucleotide polymorphisms (SNPs) on central nervous system (CNS) tumor risk.ObjectiveWe aimed to determine whether the LMO1 gene SNPs were associated with the risk of CNS tumor by applying a case‐control study with 191 cases and 248 controls in China.MethodsThe contributions of LMO1 gene SNPs to the risk of CNS tumor was evaluated by multinomial logistic regression.ResultsBased on the calculations of odds ratio (OR) and 95% confidence interval (CI), we failed to detect a significant relationship between each LMO1 gene SNP (rs110419 A>G, rs4758051 G>A, rs10840002 A>G, rs204938 A>G, and rs2168101 G>T) and CNS tumor risk, respectively. A negative association was also found in the combined effects on these five SNPs and CNS tumor risk. The stratification analysis further demonstrated the individuals with rs204938 AG/GG genotype confer to increased risk of CNS tumor compared with those with an AA genotype in males (OR: 1.74, 95% CI: 1.01–2.98, P = 0.046).InterpretationWe concluded that LMO1 gene SNPs may not strong enough to influence the risk of CNS tumor in Chinese children. More studies are required to verify this association.

Maternal and perinatal factors are associated with risk of pediatric central nervous system tumors and poorer survival after diagnosis

Central nervous system (CNS) tumors are the most common solid tumors in children. Findings on the role of maternal and perinatal factors on the susceptibility or outcome of these tumors are inconclusive. Therefore, we investigated the association between these early-life factors, risk, and survival of pediatric CNS tumors, using data from one of the world’s largest and most diverse cancer registries. Information on pediatric CNS tumor cases (n = 1950) for the period 1995–2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on birth year at a ratio of 10:1 for the same period. Evaluated maternal and perinatal variables were obtained from birth records. Unconditional logistic regression was used to generate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for etiological factors. Additionally, Cox proportional hazards regression was employed to assess adjusted hazard ratios (HRs) and 95% CIs for survival factors. The results indicated that Hispanic and non-Hispanic black mothers were less likely to have children with CNS tumors compared to non-Hispanic white mothers (OR 0.88 [95% CI 0.78–0.98] P-value = 0.019; OR 0.79 [95% CI 0.67–0.93 P-value = 0.004], respectively). Infants born large for gestational age (OR 1.26 [95% CI 1.07–1.47] P-value = 0.004) and those delivered pre-term (OR 1.19 [95% CI 1.04–1.38] P-value = 0.013) showed an increased risk of CNS tumors. Infants born by vaginal forceps or vacuum delivery had a higher risk of CNS tumors compared to those born by spontaneous vaginal delivery (OR 1.35 [95% CI 1.12–1.62] P-value = 0.002). Additionally, offspring of Hispanic and non-Hispanic black mothers showed a higher risk of death (HR 1.45 [95% CI 1.16–1.80] P-value = 0.001; HR 1.53 [95% CI 1.12–2.09] P-value = 0.008, respectively). Infants born by cesarean had a higher risk of death compared to those delivered vaginally (HR 1.28 [95% CI 1.05–1.57] P-value = 0.016). These findings indicate the important role of maternal and perinatal characteristics in the etiology and survival of these clinically significant malignancies.

No Association Between FTO Gene Polymorphisms and Central Nervous System Tumor Susceptibility in Chinese Children.

BackgroundCentral nervous system (CNS) tumor is a malignancy commonly seen occurring in childhood, worldwide. Fat mass and obesity-associated (FTO) enzyme, initially identified as an obesity-related protein, also functions as a susceptibility gene for cancers. However, predisposing effect of FTO gene single nucleotide polymorphisms (SNPs) on CNS tumor risk remains unknown.MethodsHerein, we genotyped 314 CNS tumor patients and 380 healthy controls samples from three hospitals to explore whether FTO gene SNPs impact CNS tumor risk. TaqMan SNP genotyping assay was applied for the genotyping. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from multinomial logistic regression, were applied to determine the associations of SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G, and rs8047395 A>G) in FTO gene with risk of CNS tumor.ResultsWe failed to detect significant associations between FTO gene SNPs and CNS tumor risk, either in single-locus or combined analysis. A significantly increased ependymoma risk was found for carriers with 3–4 risk genotypes in comparison to 0–2 risk genotypes (adjusted OR=1.94, 95% CI=1.11–3.37, P=0.020).ConclusionOur data indicated that FTO gene SNPs are unlikely to have large effects on CNS tumor risk but may have weaker effects.

Abstract 4656: Evaluating the role of early-life factors on the risk of pediatric central nervous system tumors: A registry-linkage study

Abstract Background: Central nervous system (CNS) tumors are the most common solid tumors in children and remain a significant contributor to death by disease in this population. While there is evidence that pediatric CNS tumors arise in early-life, limited knowledge is available on the role of maternal and perinatal factors in the etiology of these malignancies, which hampers prevention efforts. Therefore, we investigated the association between these early-life factors and risk of CNS tumors in children using data from Texas Cancer Registry, which is one of the world's largest and most diverse cancer registries, which may lead to the identification of modifiable risk factors. Methods: Information on pediatric CNS tumor cases (N=1950) for the period 1995-2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on year of birth at a ratio of 10:1 for the same period. Variables evaluated were obtained from birth records and included maternal race/ethnicity, maternal age, maternal education, maternal nativity, maternal residency (urban vs rural), residency on Mexican border, plurality and birth order of child, size for gestational age, term of birth, and mode of delivery. Unconditional logistic regression was used to generate an adjusted odds ratio (OR) and 95% confidence interval (CI) testing the association between each factor and CNS tumors overall, as well as astrocytoma (N=978) and ependymoma (N=157) subtypes individually. Results: Hispanic and non-Hispanic black mothers were less likely to have children who developed CNS tumors compared to non-Hispanic white mothers (OR: 0.88 [95%CI: 0.79-0.98]; OR: 0.78 [95%CI: 0.66-0.91], respectively). Conversely, infants born large for gestational age (OR: 1.26 [95%CI: 1.08-1.48]) as well as those delivered pre-term (&amp;lt;37 weeks) (OR: 1.18 [95%CI: 1.03-1.36]) showed an increased risk of CNS tumors compared to the respective reference groups. Compared to women with spontaneous vaginal delivery, those with vaginal forceps or vacuum delivery were more likely to have children that developed CNS tumors (OR: 1.35 [95%CI: 1.12-1.62]). This was also true for cesarean delivery, but the confidence interval included the null (OR: 1.10 [95%CI: 0.99-1.22]). Effect estimates for pre-term birth as well as vaginal forceps or vacuum delivery were stronger for astrocytomas. An increased risk of ependymoma subtype was found for offspring of native-born Mexican mothers compared to mothers born in the United States (OR: 1.67 [95%CI: 1.03-2.71]), while a decreased risk of this subtype was detected for children of mothers with education greater than high school (OR: 0.54 [95%CI: 0.35-0.82]). Conclusions: Overall, several maternal and perinatal factors were associated with pediatric CNS tumors, indicating the important role of these characteristics in the etiology of these clinically significant malignancies. Citation Format: Maral Adel Fahmideh, Erin C. Peckham-Gregory, Jeremy M. Schraw, Murali Chintagumpala, Stephen C. Mack, Philip J. Lupo, Michael E. Scheurer. Evaluating the role of early-life factors on the risk of pediatric central nervous system tumors: A registry-linkage 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 4656.

The association between high birth weight and the risks of childhood CNS tumors and leukemia: an analysis of a US case-control study in an epidemiological database

BackgroundHigh birth weight (BW), 4000 g or larger, is an established risk factor for childhood leukemia. However, its association with central nervous system (CNS) tumor risk is yet unclear. The present study examined it, analyzing data obtained from a case-control study conducted among three states from the US. The association with childhood leukemia risk was also further examined.MethodsIn this study, a data set provided by the Comprehensive Epidemiologic Data Resource was analyzed with an official permission. The original case-control study was conducted to examine the association between paternal preconception exposure to ionizing radiation and childhood cancer risk. Cases with childhood cancer were mainly ascertained from local hospitals, and controls were selected, matched with birth year (1-year category), county of residence, sex, ethnicity and maternal age (+/−2 years). Since the ID numbers were unavailable, conventional logistic analyses were conducted adjusting for those matching variables except for the county of residence. In addition to those variables, gestational age, age at diagnosis and study sites as covariables were included in the logistic models.ResultsAnalyzed subjects were 72 CNS tumor cases, 124 leukemia cases and 822 controls born from 1945 to 1989. The odds ratios (ORs) of CNS tumor risk for children with low BWs (<2500 g) and high BWs (>4000 g) were 2.0 (95% confidence interval [CI]) = 0.7, 5.9) and 2.5 (95%CI = 1.2, 5.2)], respectively. When high-BW children were restricted to those who were large for gestational age (LGA), the OR for high-BW children remained similar (OR = 2.7; 95%CI = 1.1, 6.2). On the other hand, the ORs of leukemia risk for children with low and high BWs were 0.8 (95%CI = 0.2, 3.0) and 1.4 (95%CI = 0.7, 2.6), respectively. In the normal range of BW (2500–4000 g), higher BW was positively associated with CNS tumor risk (beta = 0.0011, p for trend = 0.012). However, the association with leukemia risk was not significant (beta = −0.0002, p for trend = 0.475).ConclusionHigh-BW and LGA children had an elevated childhood CNS tumor risk. In the normal BW range, the BW itself was positively related to CNS tumor risk. No significant association between BW and childhood leukemia risk was observed in this study.

Association between nonsteroidal anti-inflammatory drugs use and risk of central nervous system tumors: a dose-response meta analysis.

Although studies have examined the association between nonsteroidal anti-inflammatory drugs (NSAIDs) use and central nervous system (CNS) tumors risk, the results are inconclusive. Here, we conducted a dose-response meta-analysis in order to investigate the correlation between NSAIDs use and CNS tumors risk. Up to July 2017, 12 studies were included in current meta-analysis. NSAIDs use was significantly associated with a lower risk of CNS tumors. Furthermore, non-aspirin NSAIDs or aspirin use are significantly associated with a lower risk of CNS tumors. Additionally, NSAIDs use was associated with significantly a lower risk of glioma, glioblastoma but not meningioma. Subgroup analysis showed consistent findings. Furthermore, a significant dose-response relationship was observed between NSAIDs use and CNS tumors risk. Increasing cumulative 100 defined daily dose of NSAIDs use was associated with a 5% decrement of CNS tumors risk, increasing NSAIDs or non-aspirin NSAIDs or aspirin use (per 3 prescriptions increment) was associated with a 7%, 7%, 10% decrement of CNS tumors risk, increasing per 2 year of duration of NSAIDs or non-aspirin NSAIDs or aspirin use was associated with a 6%, 8%, 6% decrement of CNS tumors risk. Considering these promising results, NSAIDs use might provide helpful for reducing CNS tumors risk. Large sample size and different ethnic population are warranted to validate this association.

Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant: A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR)

Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent solid tumors, including central nervous system (CNS) tumors. The risk of CNS tumors after HCT in pediatric HCT recipients is not known. We evaluated the incidence and risk factors for CNS tumors in pediatric recipients of allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research between 1976 and 2008. A case control design was used. There were no CNS tumors in the nonmalignant cohort (n = 4543) or in those undergoing HCT for solid tumors (n = 26). There were 59 CNS tumors in 8720 patients transplanted for hematologic malignancies. In comparison with the general population, pediatric HCT recipients with hematologic malignancies had a 33 times higher than expected rate of CNS tumors (95% confidence interval, 22.98 to 45.77; P < .0001). The cumulative incidence of subsequent CNS tumors was 1.29% (95% confidence interval .87 to 1.87) at 20 years after HCT. Significant risk factors in the entire cohort were having an unrelated donor (HR, 3.35; P = .0002) and CNS disease before HCT for both acute lymphoblastic leukemia (HR, 8.21; P = .0003) and acute myeloid leukemia (HR, 6.21; P = .0174). Analysis of the matched cohort showed having an unrelated donor transplant (HR, 4.79; P = .0037), CNS disease before HCT (HR, 7.67; P = .0064), and radiotherapy exposure before conditioning (HR, 3.7; P = .0234) to be significant risk factors. Chronic graft-versus-host disease was associated with a lower risk (HR, .29; P = .0143). Survivors of HCT for nonmalignant diseases did not show an increased incidence of CNS tumors, whereas survivors of hematologic malignancies have a markedly increased incidence of CNS tumors that warrants lifelong surveillance.

Menopausal hormone therapy and central nervous system tumor risk: large UK prospective study and meta-analysis.

Female sex hormones are thought to affect women's risk of developing central nervous system (CNS) tumors. Some have reported an increased risk in users of menopausal hormone therapy (HT) but evidence is limited. In the UK General Practice Research Database we compared prospectively collected information on HT prescriptions in women aged 50-79 years with CNS tumors diagnosed in 1987-2011 with that in matched controls (four per case). Relative risks (RRs) in relation to prescribed HT were calculated overall and by CNS tumor subtype. Statistical tests are two-sided. For all CNS tumors (n = 3,500), glioma (n = 689), meningioma (n = 1,197), acoustic neuroma (n = 439), and pituitary tumors (n = 273) adjusted RRs for women prescribed HT versus not were, respectively, 1.21 (95% confidence intervals (CI) = 1.10-1.32, p < 0.0001), 1.14 (0.93-1.40, p = 0.2), 1.30 (1.11-1.51, p = 0.001), 1.37 (1.06-1.75, p = 0.01), and 1.35 (0.99-1.85, p = 0.06). There was no significant difference in risk by tumor subtype (p(heterogeneity) = 0.6). A meta-analysis was conducted, combining our results with those from other published studies with prospectively collected exposure information. The meta-analyses yielded significantly increased risks for all CNS tumors, glioma and meningioma in users of estrogen-only [1.35 (1.22-1.49), 1.23 (1.06-1.42) and 1.31 (1.20-1.43), respectively] but not estrogen-progestin HT [1.09 (0.99-1.19), 0.92 (0.78-1.08) and 1.05 (0.95-1.16), respectively]; these differences were statistically significant (p < 0.005 for each tumor type). There was no significant difference between glioma and meningioma risk in users of estrogen-only HT. The totality of the available evidence suggests an increased risk of all CNS tumors (and of glioma and meningioma separately) in users of estrogen-only HT. Absolute excess risk (2 per 10,000 users over 5 years) is small.

Asthma and risk of brain cancer in children

Little is known about the causes of central nervous system tumors in children. An inverse association between asthma and brain cancer was found in adults, but there is a dearth of studies in children. The goal of this study was to evaluate the association between asthma and brain cancer in children. Two hundred and seventy-two cases of children with brain tumor diagnosed between 0 and 14 years of age in the Province of Québec, Canada, between 1980 and 1999 and 272 incidence density-matched controls were included in the study. The parents of cases and controls were interviewed by phone using structured questionnaires. Besides asthma in children, family history of asthma, the presence of other atopies, and medication intake were also investigated. Conditional logistic regression was used to analyze the data. Brain tumor risk was decreased in children with asthma (OR, 0.55; CI 95%, 0.33-0.93), with eczema (OR, 0.52; CI 95%, 0.17-1.57), and with both asthma and eczema (OR, 0.76; CI 95%, 0.18-3.2). Maternal or sibling asthma did not modify the effect of asthma on central nervous system (CNS) tumors, while father's asthma seemed to increase the risk, but numbers were small. Antiasthma medications such as inhaled corticosteroid and beta agonists seemed to increase the risk of CNS tumors (OR for steroids, 2.55; CI 95%, 0.79-8.20 and OR for inhaled beta agonist, 1.62; CI 95%, 0.57-4.63). This study strengthens the hypothesis of inverse association between asthma and brain cancer in children, but family history and medications for asthma need further investigation.

Fetal Growth, Preterm Birth, Neonatal Stress and Risk for CNS Tumors in Children: A Nordic Population- and Register-Based Case-Control Study

The peak incidence of central nervous system (CNS) tumors in childhood indicates that intrauterine or neonatal characteristics are potential risk factors or symptoms of early onset of disease. We conducted a registry-based case-control study nested in the childhood populations of Denmark, Finland, Sweden, and Norway on the association between indicators of fetal growth and neonatal stress and childhood CNS tumor risk diagnosed during the period 1985-2006. Each of the 3,443 cases was matched individually on date of birth, sex, and country to five controls sampled randomly from population registries. Information on birth characteristics was obtained from national birth registries. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) by conditional logistic regression analyses. We observed a U-shaped relation between risk for CNS tumors and birthweight, at >4.5 kg (OR, 1.27; 95% CI, 1.03-1.55) and <2.0 kg (OR, 1.50; 95% CI, 1.13-1.99), the latter being attenuated after adjustment for gestational age. Moreover, small-for-gestational age (OR, 1.28; 95% CI, 0.98-1.66) and large-for-gestational age (OR, 1.26; 95% CI, 1.02-1.55) were both associated with CNS tumors. The OR for preterm births was increased per 1-week decrease in gestational age (OR, 1.58; 95% CI, 1.04-2.44). Increased ORs were also observed for head circumference >38 cm (1.80; 95% CI, 1.18-2.74), 5-minute Apgar score <7 (1.44; 95% CI, 0.98-2.12), and breech presentation (1.33; 95% CI, 1.04-1.69). The observed associations varied little by histologic subgroup. This study supports intrauterine or neonatal onset of childhood CNS tumors. The findings provide insight into the natural history of childhood CNS tumors indicating an early onset or, alternatively, potentially harmful exposures in the neonatal period that might be preventable.

Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy and childhood malignant central nervous system tumours: the ESCALE study (SFCE)*

Parental smoking and maternal alcohol and caffeinated beverage consumption are prevalent exposures which may play a role, either directly or through their influence on metabolism, in the aetiology of childhood malignant central nervous system (CNS) tumours. The hypothesis was investigated in the Epidemiological Study on childhood Cancer and Leukemia ESCALE study, a national population-based case-control study carried out in France in 2003-2004. The study included 209 incident cases of CNS tumours and 1681 population-based controls, frequency matched with the cases by age and sex. The data were collected through a standardized telephone interview of the biological mothers. No association between maternal smoking during pregnancy and CNS tumours [odds ratio (OR): 1.1 (0.8-1.6)] was observed. Paternal smoking during the year before birth was associated with CNS tumours (P for trend=0.04), particularly astrocytomas [OR: 3.1 (1.3-7.6)]. Maternal alcohol consumption during pregnancy was not associated with CNS tumours. Associations between ependymomas and the highest consumption of coffee [OR: 2.7 (0.9-8.1)] and tea [OR: 2.5 (1.1-5.9)] were observed. A strong association between CNS tumours and the highest maternal consumption of both coffee and tea during pregnancy was observed [OR: 4.4 (1.5-13)]. The results constitute additional evidence for a role of paternal smoking and suggest that maternal coffee and tea consumption during pregnancy may also increase the risk of CNS tumours. The study does not suggest an increased risk of CNS tumours related to alcohol consumption during pregnancy.

Risk of cancer in children with the diagnosis immaturity at birth

Cancer risk in children born before term has been assessed in a large number of case-control studies but very rarely in cohort studies. We carried out a cohort study of 35 178 children with the diagnosis immaturity at birth in the Hospital Discharge Register during 1977-89. The children were followed for cancer in the Danish Cancer Registry until 1994 and comparisons were made with incidence rates for all children in Denmark. The 64 observed cases of childhood cancer in the cohort corresponded closely to the expected number {standardised incidence ratio (SIR) = 1.03; [95% confidence interval (CI) 0.80, 1.32]}. The only cancer site with an observed number that deviated significantly from the expected number was central nervous system (CNS) tumours (26 cases observed; SIR = 1.57; [95% CI 1.02, 2.30]) in particular medulloblastoma (9 cases observed; SIR = 3.1; [95% CI 1.4, 5.9]). In a nested case-control study of the CNS tumours, we found that more cases than controls had been exposed to diagnostic X-rays, but the result was not significant. Surprisingly, for those born before term, the risk of CNS tumours increased with increasing gestational age in the nested case-control data. Our results are in line with previous evidence that children born before term are not at increased risk for childhood cancer in general. An explanation behind the excess of CNS tumours could not be identified, but the effect of diagnostic X-rays in newborns may deserve further attention.

Brain and other central nervous system tumors: rates, trends, and epidemiology.

Reports that central nervous system (CNS) cancer rates are increasing have prompted debate on whether secular trends reflect environmental changes related to etiology or artifacts of case ascertainment. We present the most recent data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program on incidence rates and trends of CNS malignancies, including primary CNS lymphomas, and on survival probability. We discuss the new 2000 standard for adjusting rates; underreporting of CNS tumor rates resulting from the exclusion of nonmalignancies in most cancer registries; and information on CNS tumor risk factors, including concerns related to nonionizing electromagnetic fields and wireless mobile telephones.

Cancer risk in a cohort of polio patients.

Poliomyelitis has hypothetically been associated with an increased risk of central nervous system (CNS) tumors. The present study was performed to examine not only the risk of CNS tumors but also the overall risk of cancer among a cohort of 5,883 polio patients. Patients diagnosed with acute poliomyelitis in the Danish capital, Copenhagen, between 1919 and 1954 were identified and followed with respect to cancer. Information on vital status and cancer diagnoses was obtained through linkage with the Danish Civil Registration System and the Danish Cancer Registry, respectively. The ratio of observed number of cancers to the number expected from population-based incidence rates, i.e., the standardized incidence ratio (SIR), served as measure of the relative cancer risk. Overall, 717 cases of cancer were observed among 5,883 polio patients during 249,084 person-years of follow-up vs. an expected number of 645 (SIR = 1.11 [95% confidence interval 1.03 to 1.20])). The increased risk was restricted to female polio patients (SIR = 1.18 [1.07 to 1.30]), among whom the risk was particularly high for breast cancer (SIR = 1.35 [1.12 to 1.61]) and for skin cancer (SIR = 1.66 [1.32 to 2.07]). The risk of breast cancer was highest among women with a history of paralytic polio (SIR = 1.62 [1.24 to 2.10]). The observed number of CNS tumors did not exceed the expected (SIR = 1.09 [0.72 to 1.60]). Women diagnosed with poliomyelitis, in particular paralytic polio, may be at increased risk of breast cancer. There was no association between malignancies of the CNS and poliomyelitis.