Changes in survival over time for primary brain and other CNS tumors in the United States, 2004-2017.

PURPOSE: Despite advances in cancer diagnosis and clinical care, survival for many primary brain and other central nervous system (CNS) tumors remain poor. This study performs a comprehensive survival analysis on these tumors. METHODS: Survival differences were determined utilizing the National Program of Cancer Registries Survival Analytic file for primary brain and CNS tumors. Overall survival and survival of the 5 most common histopathologies, within specific age groups, were determined. Overall survival was compared for three time periods: 2004-2007, 2008-2012, and 2013-2017. Survival differences were evaluated using Kaplan-Meier and multivariable Cox proportional hazards models. Models were adjusted for sex, race/ethnicity, and treatment. Malignant and non-malignant brain tumors were assessed separately. RESULTS: Among malignant brain and CNS tumor patients overall, there were notable differences in survival by time period among all age groups. Similar differences were noted in non-malignant brain and CNS tumor patients, except for adults (aged 40-64 years), where no survival changes were observed. Survival differences varied within specific histopathologies across age groups. There were improvements in survival in 2008-2012 and 2013-2017, when compared to 2004-2007, in children, AYA, and older adults with malignant tumors, and among older adults with non-malignant tumors. CONCLUSION: Overall survival for malignant brain and other CNS tumors improved slightly in 2013-2017 for all age groups as compared to 2004-2007. Significant changes were observed for non-malignant brain and other CNS tumors among older adults. Information regarding survival over time can be utilized to identify population level effects of diagnostic and treatment improvements.

CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018.

The CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018 comprehensively describes the current population-based incidence of primary malignant and non-malignant brain and other CNS tumors in children and adolescents ages 0-19 years, collected and reported by central cancer registries covering approximately 100% of the United States population. Overall, brain and other CNS tumors are the most common solid tumor, the most common cancer, and the most common cause of cancer death in children and adolescents ages 0-19 years. This report aims to serve as a useful resource for researchers, clinicians, patients, and families.

The shared genetic architecture between epidemiological and behavioral traits with lung cancer.

The complex polygenic nature of lung cancer is not fully characterized. Our study seeks to identify novel phenotypes associated with lung cancer using cross-trait linkage disequilibrium score regression (LDSR). We measured pairwise genetic correlation (rg) and SNP heritability (h2) between 347 traits and lung cancer risk using genome-wide association study summary statistics from the UKBB and OncoArray consortium. Further, we conducted analysis after removing genomic regions previously associated with smoking behaviors to mitigate potential confounding effects. We found significant negative genetic correlations between lung cancer risk and dietary behaviors, fitness metrics, educational attainment, and other psychosocial traits. Alcohol taken with meals (rg = - 0.41, h2 = 0.10, p = 1.33 × 10-16), increased fluid intelligence scores (rg = - 0.25, h2 = 0.22, p = 4.54 × 10-8), and the age at which full time education was completed (rg = - 0.45, h2 = 0.11, p = 1.24 × 10-20) demonstrated negative genetic correlation with lung cancer susceptibility. The body mass index was positively correlated with lung cancer risk (rg = 0.20, h2 = 0.25, p = 2.61 × 10-9). This analysis reveals shared genetic architecture between several traits and lung cancer predisposition. Future work should test for causal relationships and investigate common underlying genetic mechanisms across these genetically correlated traits.

Partitioned glioma heritability shows subtype-specific enrichment in immune cells.

BACKGROUND: Epidemiological studies of adult glioma have identified genetic syndromes and 25 heritable risk loci that modify individual risk for glioma, as well increased risk in association with exposure to ionizing radiation and decreased risk in association with allergies. In this analysis, we assess whether there is a shared genome-wide genetic architecture between glioma and atopic/autoimmune diseases. METHODS: Using summary statistics from a glioma genome-wide association studies (GWAS) meta-analysis, we identified significant enrichment for risk variants associated with gene expression changes in immune cell populations. We also estimated genetic correlations between glioma and autoimmune, atopic, and hematologic traits using linkage disequilibrium score regression (LDSC), which leverages genome-wide single-nucleotide polymorphism (SNP) associations and patterns of linkage disequilibrium. RESULTS: Nominally significant negative correlations were observed for glioblastoma (GB) and primary biliary cirrhosis (rg = -0.26, P = .0228), and for non-GB gliomas and celiac disease (rg = -0.32, P = .0109). Our analyses implicate dendritic cells (GB pHM = 0.0306 and non-GB pHM = 0.0186) in mediating both GB and non-GB genetic predisposition, with GB-specific associations identified in natural killer (NK) cells (pHM = 0.0201) and stem cells (pHM = 0.0265). CONCLUSIONS: This analysis identifies putative new associations between glioma and autoimmune conditions with genomic architecture that is inversely correlated with that of glioma and that T cells, NK cells, and myeloid cells are involved in mediating glioma predisposition. This provides further evidence that increased activation of the acquired immune system may modify individual susceptibility to glioma.

The Shared Genetic Architectures Between Lung Cancer and Multiple Polygenic Phenotypes in Genome-Wide Association Studies.

BACKGROUND: Prior genome-wide association studies have identified numerous lung cancer risk loci and reveal substantial etiologic heterogeneity across histologic subtypes. Analyzing the shared genetic architecture underlying variation in complex traits can elucidate common genetic etiologies across phenotypes. Exploring pairwise genetic correlations between lung cancer and other polygenic traits can reveal the common genetic etiology of correlated phenotypes. METHODS: Using cross-trait linkage disequilibrium score regression, we estimated the pairwise genetic correlation and heritability between lung cancer and multiple traits using publicly available summary statistics. Identified genetic relationships were also examined after excluding genomic regions known to be associated with smoking behaviors, a major risk factor for lung cancer. RESULTS: We observed several traits showing moderate single nucleotide polymorphism-based heritability and significant genetic correlations with lung cancer. We observed highly significant correlations between the genetic architectures of lung cancer and emphysema/chronic bronchitis across all histologic subtypes, as well as among lung cancer occurring among smokers. Our analyses revealed highly significant positive correlations between lung cancer and paternal history of lung cancer. We also observed a strong negative correlation with parental longevity. We observed consistent directions in genetic patterns after excluding genomic regions associated with smoking behaviors. CONCLUSIONS: This study identifies numerous phenotypic traits that share genomic architecture with lung carcinogenesis and are not fully accounted for by known smoking-associated genomic loci. IMPACT: These findings provide new insights into the etiology of lung cancer by identifying traits that are genetically correlated with increased risk of lung cancer.