Elevated meningioma risk among individuals who are Non-Hispanic Black is strongest for grade 2-3 tumors and synergistically modified by male sex.

Background: Meningioma risk factors include older age, female sex, and African-American race. There are limited data exploring how meningioma risk in African-Americans varies across the lifespan, interacts with sex, and differs by tumor grade. Methods: The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry covering the entire U.S. population. Meningioma diagnoses from 2004-2019 were used to calculate incidence rate ratios (IRRs) for non-Hispanic Black individuals (NHB) compared to non-Hispanic white individuals (NHW) across 10-year age intervals, and stratified by sex and by WHO tumor grade. Results: 53,890 NHB individuals and 322,373 NHW individuals with an intracranial meningioma diagnosis were included in analyses. Beginning in young adulthood, the NHB-to-NHW IRR was elevated for both grade 1 and grade 2/3 tumors. The IRR peaked in the seventh decade of life regardless of grade, and was higher for grade 2/3 tumors (IRR=1.57; 95% CI: 1.46-1.69) than grade 1 tumors (IRR=1.27; 95% CI: 1.25-1.30) in this age group. The NHB-to-NHW IRR was elevated in females (IRR=1.17; 95% CI: 1.16-1.18) and further elevated in males (IRR=1.28; 95% CI: 1.26-1.30), revealing synergistic interaction between NHB race/ethnicity and male sex (P Interaction =0.001). Conclusions: Relative to NHW individuals, NHB individuals are at elevated risk of meningioma from young adulthood through old age. NHB race/ethnicity conferred higher risk of meningioma among men than women, and higher risk of developing WHO grade 2/3 tumors. Results identify meningioma as a significant source of racial disparities in neuro-oncology and may help to improve preoperative predictions of meningioma grade.

Genome-wide Polygenic Risk Scores Predict Risk of Glioma and Molecular Subtypes.

BACKGROUND: Polygenic risk scores (PRS) aggregate the contribution of many risk variants to provide a personalized genetic susceptibility profile. Since sample sizes of glioma genome-wide association studies (GWAS) remain modest, there is a need to efficiently capture genetic risk using available data. METHODS: We applied a method based on continuous shrinkage priors (PRS-CS) to model the joint effects of over 1 million common variants on disease risk and compared this to an approach (PRS-CT) that only selects a limited set of independent variants that reach genome-wide significance (P<5×10-8). PRS models were trained using GWAS stratified by histological (10,346 cases, 14,687 controls) and molecular subtype (2,632 cases, 2,445 controls), and validated in two independent cohorts. RESULTS: PRS-CS was generally more predictive than PRS-CT with a median increase in explained variance (R2) of 24% (interquartile range=11-30%) across glioma subtypes. Improvements were pronounced for glioblastoma (GBM), with PRS-CS yielding larger odds ratios (OR) per standard deviation (OR=1.93, P=2.0×10-54 vs. OR=1.83, P=9.4×10-50) and higher explained variance (R2=2.82% vs. R2=2.56%). Individuals in the 80th percentile of the PRS-CS distribution had significantly higher risk of GBM (0.107%) at age 60 compared to those with average PRS (0.046%, P=2.4×10-12). Lifetime absolute risk reached 1.18% for glioma and 0.76% for IDH wildtype tumors for individuals in the 95th PRS percentile. PRS-CS augmented the classification of IDH mutation status in cases when added to demographic factors (AUC=0.839 vs. AUC=0.895, PΔAUC=6.8×10-9). CONCLUSIONS: Genome-wide PRS has potential to enhance the detection of high-risk individuals and help distinguish between prognostic glioma subtypes.

Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations.

BACKGROUND: Canine and human osteosarcoma are similar in clinical presentation and tumor genomics. Giant breed dogs experience elevated osteosarcoma incidence, and taller stature remains a consistent risk factor for human osteosarcoma. Whether evolutionarily conserved genes contribute to both human and canine osteosarcoma predisposition merits evaluation. METHODS: A multi-center sample of childhood osteosarcoma patients and controls underwent genome-wide genotyping and imputation. Ancestry-adjusted SNP associations were calculated within each dataset using logistic regression, then meta-analyzed across the three datasets, totaling 1091 patients and 3026 controls. Ten regions previously associated with canine osteosarcoma risk were mapped to the human genome, spanning ∼6 Mb. We prioritized association testing of 5985 human SNPs mapping to candidate osteosarcoma risk regions detected in Irish wolfhounds, the largest dog breed studied. Secondary analyses explored 6289 additional human SNPs mapping to candidate osteosarcoma risk regions identified in Rottweilers and greyhounds. RESULTS: Fourteen SNPs were associated with human osteosarcoma risk after adjustment for multiple comparisons, all within a 42 kb region of human Chromosome 7p12.1. The lead variant was rs17454681 (OR=1.25, 95 %CI: 1.12-1.39; P=4.1×10-5), and independent risk variants were not observed in conditional analyses. While the associated region spanned 2.1 Mb and contained eight genes in Irish wolfhounds, associations were localized to a 50-fold smaller region of the human genome and strongly implicate GRB10 (growth factor receptor-bound protein 10) in canine and human osteosarcoma predisposition. PheWAS analysis in UK Biobank data identified noteworthy associations of the rs17454681 risk allele with varied measures of height and pubertal timing. CONCLUSIONS: Our comparative oncology analysis identified a novel human osteosarcoma risk allele near GRB10, a growth inhibitor that suppresses activated receptor tyrosine kinases including IGF1R, PDGFRB, and EGFR. Epidemiologists may benefit from leveraging cross-species comparisons to identify haplotypes in highly susceptible but genetically homogenous populations of domesticated animals, then fine-mapping these associations in diverse human populations.

Atopy improves survival and decreases risk of brain metastasis in cutaneous melanoma.

Importance: Development of new therapies in melanoma has increased survival, and as a result more patients are living to develop brain metastasis (BrM). Identifying patients at increased risk of BrM is therefore of significant public health importance. Objective: To determine whether history of atopy is associated with improved survival or reduced incidence of BrM in cutaneous melanoma. Design: A retrospective cohort study conducted from June 2022 to March 2024. Setting: Population-based in states with Surveillance, Epidemiology and End Results (SEER) supported cancer registries. Participants: Individuals (≥65 years) diagnosed with cutaneous melanoma between January 1, 2008 and December 31, 2017 that are participants in traditional Medicare. Exposures: Individuals were compared that had history of atopy (allergic rhinitis, atopic dermatitis, asthma, and/or allergic/atopic conjunctivitis) diagnosed prior to melanoma diagnosis, ascertained using ICD-9 or ICD-10 codes in Medicare claims. Main Outcomes and Measures: Primary endpoints were diagnosis with a BrM or death during the follow-up period. Associations between atopy and endpoints were assessed using cox proportional hazards models to estimate hazard ratios (HR) and p-values. Results: A total of 29,956 cutaneous melanoma cases were identified (median age 76, 60% male and 97% non-Hispanic White). Overall, 7.1% developed BrM during follow up. Among the 35% that had history of atopy, the most common condition was atopic dermatitis (19%). After adjustment for demographic and prognostic factors, atopy was associated with a 16% decrease in death (HR=0.84 [95%CI:0.80-0.87], pFDR<0.001). Among those with non-metastatic disease at time of diagnosis, atopy conferred a 15% decrease in cumulative incidence BrM (HR=0.85 [95%CI: 0.76-0.94], pFDR=0.006), with a 25% decrease associated with atopic dermatitis (HR=0.75 [95%CI:0.65-0.86], pFDR<0.001). Among those with metastatic disease at diagnosis (any metastatic site), only those who received immune checkpoint inhibitors had a survival benefit associated with atopy (HR=0.31, [95%CI:0.15-0.64], p=0.001 vs HR=1.41, [95%CI:0.87-2.27], p=0.165). Conclusions and Relevance: Atopy, particularly atopic dermatitis, was significantly associated with improved survival and decreased incidence of BrM. The improved survival associated with these conditions in the context of immunotherapy suggests that these conditions in the elderly may identify those with more robust immune function that may be more responsive to treatment.

CBTRUS Statistical Report: American Brain Tumor Association & NCI Neuro-Oncology Branch Adolescent and Young Adult Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020.

Recent analyses have shown that, whereas cancer survival overall has been improving, it has not improved for adolescents and young adults ages 15-39 years (AYA). The clinical care of AYA with primary brain and other central nervous system (CNS) tumors (BT) is complicated by the fact that the histopathologies of such tumors in AYA differ from their histopathologies in either children (ages 0-14 years) or older adults (ages 40+ years). The present report, as an update to a 2016 publication from the Central Brain Tumor Registry of the United States and the American Brain Tumor Association, provides in-depth analyses of the epidemiology of primary BT in AYA in the United States and is the first to provide biomolecular marker-specific statistics and prevalence by histopathology for both primary malignant and non-malignant BT in AYA. Between 2016 and 2020, the annual average age-specific incidence rate (AASIR) of primary malignant and non-malignant BT in AYA was 12.00 per 100,000 population, an average of 12,848 newly diagnosed cases per year. During the same period, an average of 1,018 AYA deaths per year were caused by primary malignant BT, representing an annual average age-specific mortality rate of 0.96 per 100,000 population. When primary BT were categorized by histopathology, pituitary tumors were the most common (36.6%), with an AASIR of 4.34 per 100,000 population. Total incidence increased with age overall; when stratified by sex, the incidence was higher in females than males at all ages. Incidence rates for all primary BT combined and for non-malignant tumors only were highest for non-Hispanic American Indian/Alaska Native individuals, whereas malignant tumors were more frequent in non-Hispanic White individuals, compared with other racial/ethnic groups. On the basis of histopathology, the most common molecularly defined tumor was diffuse glioma (an AASIR of 1.51 per 100,000). Primary malignant BT are the second most common cause of cancer death in the AYA population. Incidence rates of primary BT overall, as well as specific histopathologies, vary significantly by age. Accordingly, an accurate statistical assessment of primary BT in the AYA population is vital for better understanding the impact of these tumors on the US population and to serve as a reference for afflicted individuals, for researchers investigating new therapies, and for clinicians treating these patients.

Meningioma: International Consortium on Meningiomas (ICOM) consensus review on scientific advances & treatment paradigms for clinicians, researchers, and patients.

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and the rising availability of neuroimaging. While most exhibit non-malignant behaviour, a subset of meningiomas are biologically aggressive and lead to significant neurological morbidity and mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) working group. There also remains clinical equipoise on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas (ICOM) including field-leading experts, have prepared a comprehensive consensus narrative review directed towards clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality of life studies, and management strategies for unique meningioma patient populations. In each section we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

Sex differences in adverse events in Medicare individuals ≥ 66 years of age post glioblastoma treatment.

PURPOSE: Glioblastoma (GB) is the most common primary malignant brain tumor with the highest incidence occurring in older adults with a median age at diagnosis of 64 years old. While treatment often improves survival it brings toxicities and adverse events (AE). Here we identify sex differences in treatment patterns and AE in individuals ≥ 66 years at diagnosis with GB. METHODS: Using the SEER-Medicare dataset sex differences in adverse events were assessed using multivariable logistic regression performed to calculate the male/female odds ratio (M/F OR) and 95% confidence intervals [95% CI] of experiencing an AE adjusted for demographic variables and Elixhauser comorbidity score. RESULTS: Males with GB were more likely to receive standard of care (SOC; Surgery with concurrent radio-chemotherapy) [20%] compared to females [17%], whereas females were more likely to receive no treatment [26%] compared to males [21%]. Females with GB receiving SOC were more likely to develop gastrointestinal disorders (M/F OR = 0.76; 95% CI,0.64-0.91, p = 0.002) or blood and lymphatic system disorders (M/F OR = 0.79; 95% CI,0.66-0.95, p = 0.012). Males with GB receiving SOC were more likely to develop cardiac disorders (M/F OR = 1.21; 95% CI,1.02-1.44, p = 0.029) and renal disorders (M/F OR = 1.65; 95% CI,1.37-2.01, p < 0.001). CONCLUSIONS: Sex differences for individuals, 66 years and older, diagnosed with GB exist in treatment received and adverse events developed across different treatment modalities.

Genome-wide Polygenic Risk Scores Predict Risk of Glioma and Molecular Subtypes.

Background: Polygenic risk scores (PRS) aggregate the contribution of many risk variants to provide a personalized genetic susceptibility profile. Since sample sizes of glioma genome-wide association studies (GWAS) remain modest, there is a need to find efficient ways of capturing genetic risk factors using available germline data. Methods: We developed a novel PRS (PRS-CS) that uses continuous shrinkage priors to model the joint effects of over 1 million polymorphisms on disease risk and compared it to an approach (PRS-CT) that selects a limited set of independent variants that reach genome-wide significance (P<5×10-8). PRS models were trained using GWAS results stratified by histological (10,346 cases, 14,687 controls) and molecular subtype (2,632 cases, 2,445 controls), and validated in two independent cohorts. Results: PRS-CS was consistently more predictive than PRS-CT across glioma subtypes with an average increase in explained variance (R2) of 21%. Improvements were particularly pronounced for glioblastoma tumors, with PRS-CS yielding larger effect sizes (odds ratio (OR)=1.93, P=2.0×10-54 vs. OR=1.83, P=9.4×10-50) and higher explained variance (R2=2.82% vs. R2=2.56%). Individuals in the 95th percentile of the PRS-CS distribution had a 3-fold higher lifetime absolute risk of IDH mutant (0.63%) and IDH wildtype (0.76%) glioma relative to individuals with average PRS. PRS-CS also showed high classification accuracy for IDH mutation status among cases (AUC=0.895). Conclusions: Our novel genome-wide PRS may improve the identification of high-risk individuals and help distinguish between prognostic glioma subtypes, increasing the potential clinical utility of germline genetics in glioma patient management.

The impact of COVID-19 on 2020 monthly incidence trends of primary brain and other CNS tumors.

BACKGROUND: To mitigate disease spread, restrictions implemented in the United States surrounding the COVID-19 pandemic created an environment that led to delays in cancer diagnosis. The data needed to accurately analyze the impact of the pandemic on brain and CNS tumor incidence has not been available until now. Utilizing incidence data from the Central Brain Tumor Registry of the United States (CBTRUS) we analyzed the impact of the COVID-19 pandemic on primary brain and other CNS tumor incidence for the first year of the pandemic. METHODS: Monthly age-adjusted incidence rates and incidence trends for 2019 and 2020 were determined for age at diagnosis, sex, race, ethnicity, diagnostic confirmation, behavior, tumor histopathology, and county-level urbanization. Monthly incidence rate ratios comparing 2020 and 2019 were evaluated for the same factors. RESULTS: Overall, there was a notable decrease in incidence rates in March-May 2020 when compared to 2019. These decreases were driven by nonmalignant tumors, with a 50% incidence decrease between March 2020 and 2019. Individuals who were Black had a larger incidence decrease in early 2020 than individuals who were White. Radiographically confirmed tumors saw larger incidence decreases than histologically confirmed tumors. There were no changes in monthly incidence of glioblastoma in 2020 compared to 2019. CONCLUSIONS: These data provide evidence that disruptions in medical care, such as governmental and health care mandates, in response to the COVID-19 pandemic resulted in an overall decreased incidence of primary brain tumors in early 2020.

Childhood, adolescent, and adult primary brain and central nervous system tumor statistics for practicing healthcare providers in neuro-oncology, CBTRUS 2015-2019.

Background: The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI), is the largest aggregation of histopathology-specific population-based data for primary brain and other central nervous system (CNS) in the US. CBTRUS publishes an annual statistical report which provides critical reference data for the broad neuro-oncology community. Here, we summarize the key findings from the 2022 CBTRUS annual statistical report for healthcare providers. Methods: Incidence data were obtained from the CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results Program for 52 central cancer registries (CCRs). Survival data were obtained from 42 NPCR CCRs. All rates are per 100 000 and age-adjusted using the 2000 US standard population. Overall median survival was estimated using Kaplan-Meier models. Survival data for selected molecularly defined histopathologies are from the National Cancer Database. Mortality data are from the National Vital Statistics System. Results: The average annual age-adjusted incidence rate of all primary brain and other CNS tumors was 24.25/100 000. Incidence was higher in females and non-Hispanics. The most commonly occurring malignant and predominately non-malignant tumors was glioblastoma (14% of all primary brain tumors) and meningioma (39% of all primary brain tumors), respectively. Mortality rates and overall median survival varied by age, sex, and histopathology. Conclusions: This summary describes the most up-to-date population-based incidence, mortality, and survival, of primary brain and other CNS tumors in the US and aims to serve as a concise resource for neuro-oncology providers.

Association Between Urbanicity and Outcomes Among Patients with Spinal Cord Ependymomas in the United States.

BACKGROUND: Spinal cord ependymomas (SCEs) represent the most common intramedullary spinal cord tumors among adults. Research shows that access to neurosurgical care and patient outcomes can be greatly influenced by patient location. This study investigates the association between the outcomes of patients with SCE in metropolitan and nonmetropolitan areas. METHODS: Cases of SCE between 2004 and 2019 were identified within the Central Brain Tumor Registry of the United States, a combined dataset including the Centers for Disease Control and Prevention's National Program of Cancer Registries and National Cancer Institute's Surveillance, Epidemiology, and End Results Program data. Multivariable logistic regression models were constructed to evaluate the association between urbanicity and SCE treatment, adjusted for age at diagnosis, sex, race and ethnicity. Survival data was available from 42 National Program of Cancer Registries (excluding Kansas and Minnesota, for which county data are unavailable), and Cox proportional hazard models were used to understand the effect of surgical treatment, county urbanicity, age at diagnosis, and the interaction effect between age at diagnosis and surgery, on the survival time of patients. RESULTS: Overall, 7577 patients were identified, with 6454 (85%) residing in metropolitan and 1223 (15%) in nonmetropolitan counties. Metropolitan and nonmetropolitan counties had different age, sex, and race/ethnicity compositions; however, demographics were not associated with differences in the type of surgery received when stratified by urbanicity. Irrespective of metropolitan status, individuals who were American Indian/Alaska Native non-Hispanic and Hispanic (all races) were associated with reduced odds of receiving surgery. Individuals who were Black non-Hispanic and Hispanic were associated with increased odds of receiving comprehensive treatment. Diagnosis of SCE at later ages was linked with elevated mortality (hazard ratio = 4.85, P < 0.001). Gross total resection was associated with reduced risk of death (hazard ratio = 0.37, P = 0.004), and age did not interact with gross total resection to influence risk of death. CONCLUSIONS: The relationship between patients' residential location and access to neurosurgical care is critical to ensuring equitable distribution of care. This study represents an important step in delineating areas of existing disparities.

Association of county-level socioeconomic status with meningioma incidence and outcomes.

BACKGROUND: Prior literature suggests that individual socioeconomic status (SES) may influence incidence, treatments, and survival of brain tumor cases. We aim to conduct the first national study to evaluate the association between US county-level SES and incidence, treatment, and survival in meningioma. METHODS: The Central Brain Tumor Registry of the United States analytic dataset, which combines data from CDC's National Program of Cancer Registries (NPCR) and National Cancer Institute's Surveillance, Epidemiology, and End Results Program, was used to identify meningioma cases from 2006 to 2019. SES quintiles were created using American Community Survey data. Logistic regression models were used to evaluate associations between SES and meningioma. Cox proportional hazard models were constructed to assess the effect of SES on survival using the NPCR analytic dataset. RESULTS: A total of 409 681 meningioma cases were identified. Meningioma incidence increased with higher county-level SES with Q5 (highest quintile) having a 12% higher incidence than Q1 (incidence rate ratios (IRR) = 1.12, 95%CI: 1.10-1.14; P < .0001). The Hispanic group was the only racial-ethnic group that had lower SES associated with increased meningioma incidence (Q5: age-adjusted incidence ratio (AAIR) = 9.02, 95%CI: 8.87-9.17 vs. Q1: AAIR = 9.33, 95%CI: 9.08-9.59; IRR = 0.97, 95%CI: 0.94-1.00; P = .0409). Increased likelihood of surgical treatment was associated with Asian or Pacific Islander non-Hispanic individuals (compared to White non-Hispanic (WNH)) (OR = 1.28, 95%CI: 1.23-1.33, P < .001) and males (OR = 1.31, 95%CI: 1.29-1.33, P < .001). Black non-Hispanic individuals (OR = 0.90, 95%CI: 0.88-0.92, P < .001) and those residing in metropolitan areas (OR = 0.96, 95%CI: 0.96-0.96, P < .001) were less likely to receive surgical treatment compared to WNH individuals. Overall median survival was 137 months, and survival was higher in higher SES counties (Q5 median survival = 142 months). CONCLUSIONS: Higher county-level SES was associated with increased meningioma incidence, surgical treatment, and overall survival. Racial-ethnic stratification identified potential disparities within the meningioma population. Further work is needed to understand the underpinnings of socioeconomic and racial disparities for meningioma patients.

Impact of environment on pediatric and adult brain tumors: The 2023 Brain Tumor Epidemiology Consortium meeting report.

The Brain Tumor Epidemiology Consortium (BTEC) is an international organization with membership of individuals from the scientific community with interests related to brain tumor epidemiology including surveillance, classification, methodology, etiology, and factors associated with morbidity and mortality. The 2023 annual BTEC meeting entitled "Impact of Environment on Pediatric and Adult Brain Tumors" was held in Lexington, KY, USA on May 22 - 24, 2023. The meeting gathered scientists from the United States, Canada, Australia, and Europe and included four keynote sessions covering genomic, epigenomic, and metabolomic considerations in brain tumor epidemiology, cancer clusters, environmental risk factors, and new approaches to cancer investigation. The meeting also included three abstract sessions and a brainstorming session. A summary of the meeting content is included in this report.

Brain tumors in United States military veterans.

BACKGROUND: Comprehensive analysis of brain tumor incidence and survival in the Veteran population has been lacking. METHODS: Veteran data were obtained from the Veterans Health Administration (VHA) Medical Centers via VHA Corporate Data Warehouse. Brain tumor statistics on the overall US population were generated from the Central Brain Tumor Registry of the US data. Cases were individuals (≥18 years) with a primary brain tumor, diagnosed between 2004 and 2018. The average annual age-adjusted incidence rates (AAIR) and 95% confidence intervals were estimated per 100 000 population and Kaplan-Meier survival curves evaluated overall survival outcomes among Veterans. RESULTS: The Veteran population was primarily white (78%), male (93%), and between 60 and 64 years old (18%). Individuals with a primary brain tumor in the general US population were mainly female (59%) and between 18 and 49 years old (28%). The overall AAIR of primary brain tumors from 2004 to 2018 within the Veterans Affairs cancer registry was 11.6. Nonmalignant tumors were more common than malignant tumors (AAIR:7.19 vs 4.42). The most diagnosed tumors in Veterans were nonmalignant pituitary tumors (AAIR:2.96), nonmalignant meningioma (AAIR:2.62), and glioblastoma (AAIR:1.96). In the Veteran population, survival outcomes became worse with age and were lowest among individuals diagnosed with glioblastoma. CONCLUSIONS: Differences between Veteran and US populations can be broadly attributed to demographic composition differences of these groups. Prior to this, there have been no reports on national-level incidence rates and survival outcomes for Veterans. These data provide vital information that can drive efforts to understand disease burden and improve outcomes for individuals with primary brain tumors.

Genetic association between atopic disease and osteoarthritis.

OBJECTIVES: To evaluate the association between genetically determined risk for atopic disease and osteoarthritis (OA). METHODS: We performed linkage disequilibrium (LD) score regression using 1000 Genomes Project European samples as a reference for patterns of genome-wide LD. Summary statistics for atopic disease traits were obtained from the UK Biobank. We generated a pairwise genetic correlation between OA and traits for atopic disease to estimate the genetic correlation between traits (rg) and heritability for each trait. The association between atopy-related traits and OA was examined using Mendelian randomization (MR) on summary statistics; we reported inverse-variance weighted (IVW), MR-Egger, maximum likelihood estimation, weighted median, and weighted mode. RESULTS: There was a significant positive correlation between the genome-wide genetic architecture of asthma and all OA traits. Using the IVW (random effects), there was a significant association between asthma and knee OA ((odds ratio) OR = 1.04, 95% (confidence interval) CI 1.01-1.08, p = 0.0169). Using IVW (fixed effects), significant associations were identified between knee OA and allergic disease (OR = 1.07, 95% CI 1.01-1.14, p = 0.0342), allergic rhinitis (OR = 1.07, 95% CI 1.00-1.13, p = 0.0368), and asthma (OR = 1.04, 95% CI 1.01-1.07, p = 0.0139), as well as for OA at any site and asthma (OR = 1.02, 95% CI 1.00-1.04, p = 0.0166). CONCLUSIONS: We found a significant correlation between the overall genetic architecture of asthma and OA, as well as an increased risk of developing OA in patients with genetic variants associated with asthma and allergic rhinitis; predominately, this risk was for the development of knee OA. These results support a causal relationship between asthma and/or allergic rhinitis and knee OA.

Association between county-level socioeconomic status and the incidence of and surgical treatment for pituitary adenoma.

OBJECTIVE: The objective of this study was to evaluate the association between county-level socioeconomic status (SES) and the incidence of and surgical treatment for pituitary adenoma (PA). METHODS: Using the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results database, the authors identified the average annual age-adjusted incidence rates and calculated odds ratios (ORs) for surgical treatment of PA, stratified by a county-level index for SES, race/ethnicity, metropolitan status, and other confounders. RESULTS: From 2006 to 2018, 167,121 PA cases were identified. There was no significant trend in the incidence of PA by county-level SES overall (incidence rate ratio [IRR] 0.98, 95% CI 0.96-1.00, p = 0.05, comparing highest to lowest quintile of SES). Among Asian or Pacific Islander (API; IRR 0.82, 95% CI 0.71-0.95, p = 0.007) and American Indian/Alaska Native (AIAN) participants (IRR 0.82, 95% CI 0.71-0.95, p = 0.009), the incidence of PA was statistically significantly lower with higher SES, while among Black individuals, the incidence of PA was higher with higher SES (IRR 1.10, 95% CI 1.05-1.15, p < 0.001, comparing 5th to 1st quintile of SES). Higher SES quintile was associated with surgical treatment of PA (OR 1.04, 95% CI 0.99-1.09, comparing highest to lowest quintile, p value for trend = 0.02). Males were more likely than females to undergo surgery (OR 1.50, 95% CI 1.47-1.53, p < 0.001), and Black (OR 0.89, 95% CI 0.86-0.91, p < 0.001) and AIAN individuals (OR 0.88, 95% CI 0.78-0.99, p = 0.04) were less likely to undergo surgery than White individuals, whereas API individuals were more likely to undergo surgery (OR 1.15, 95% CI 1.09-1.21, p < 0.001). CONCLUSIONS: Higher county-level SES in the US was associated with a higher incidence of PA among Black individuals, but not among White individuals, while API and AIAN individuals had a lower PA incidence with higher SES. After multivariable adjustment, higher county-level SES was associated with surgical treatment of PA, and White and API individuals were significantly more likely to undergo surgery than Black or AIAN individuals.

Capturing evolving definitions of 12 select rare CNS tumors: a timely report from CBTRUS and NCI-CONNECT.

PURPOSE: Incidence, prevalence, and survival are population-based statistics describing cancer burden. The National Cancer Institute's (NCI) Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) specializes in tumor biology and outcomes for 12 rare CNS tumor types selected for their importance in adults, research interest, or potential for targeted treatment. The aim of this study was to update incidence, prevalence, and survival statistics for these tumors. METHODS: The Central Brain Tumor Registry of the United States (CBTRUS) database, a combined dataset of Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology and End Results (SEER) data, was used to calculate average annual age-adjusted incidence rates (AAAIR) per 100,000 population overall and by sex, race-ethnicity, and age for diagnosis years 2008-2019. Incidence time trends were calculated for diagnosis years 2004-2019. NPCR data were used to calculate relative survival rates. Point prevalence on December 31, 2019 was estimated using annual age-specific incidence and survival. RESULTS: AAAIR was 1.47 per 100,000 for these tumors combined, with highest incidence in ependymomas (AAAIR = 0.41/100,000). Most tumor types were more common in males, adults (ages 40 + years) or children (ages < 15 years), and non-Hispanic White individuals. Ependymomas were the most prevalent tumor type (19,320 cases) followed by oligodendrogliomas (14,900 cases). Ependymomas had the highest five-year survival (90.6%) and primary CNS sarcomas the lowest (7.7%). CONCLUSIONS: These data provide means to measure the impact of clinical care and evaluate new therapies and the evolving histopathology definitions in rare CNS tumor types.

CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.83 per 100,000 population (malignant AAAIR=6.94 and non-malignant AAAIR=17.88). This overall rate was higher in females compared to males (27.85 versus 21.62 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.24 versus 22.61 per 100,000). Gliomas accounted for 26.3% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.9% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (40.8% of all tumors and 56.2% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.13 per 100,000 population. There were 86,030 deaths attributed to malignant brain and other CNS tumors between 2016 and 2020. This represents an average annual mortality rate of 4.42 per 100,000 population and an average of 17,206 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, for a non-malignant brain and other CNS tumor the five-year relative survival rate was 91.8%.

Heritable Traits and Lung Cancer Risk: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Lung cancer is a complex polygenic disorder. Analysis with Mendelian randomization (MR) allows for genetically predicted risks to be estimated between exposures and outcomes. METHODS: We analyzed 345 heritable traits from the United Kingdom Biobank and estimated their associated effects on lung cancer outcomes using two sample MR. In addition to estimating effects with overall lung cancer, adenocarcinoma, small cell lung cancer, and squamous cell lung cancers, we performed conditional effect modeling with multivariate MR (MVMR) and the traits of alcohol use, smoking initiation, average pre-tax income, and educational attainment. RESULTS: Univariate MR provided evidence for increased age at first sexual intercourse (OR, 0.55; P = 6.15 × 10-13), educational attainment (OR, 0.24; P = 1.07 × 10-19), average household income (OR, 0.58; P = 7.85 × 10-05), and alcohol usually taken with meals (OR, 0.19; P = 1.06 × 10-06) associating with decreased odds of overall lung cancer development. In contrast, a lack of additional educational attainment (OR, 8.00; P = 3.48 × 10-12), body mass index (OR, 1.28; P = 9.00 × 10-08), pack years smoking as a proportion of life span (OR, 9.93; P = 7.96 × 10-12), and weekly beer intake (OR, 3.48; P = 4.08 × 10-07) were associated with an increased risk of overall lung cancer development. CONCLUSIONS: Many heritable traits associated with an increased or inverse risk of lung cancer development. Effects vary based on histologic subtype and conditional third trait exposures. IMPACT: We identified several heritable traits and presented their genetically predictable impact on lung cancer development, providing valuable insights for consideration.