RESUMO
BACKGROUND: Although molecular biomarkers have significantly advanced precision oncology in glioblastoma, the prevalence of these biomarkers by race remains underexplored. This study aims to characterize the genomic alterations in glioblastoma across Asian, Black, and White patients, offering insights into racial disparities that may influence treatment outcomes and disease progression. METHODS: Analyzing data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange database V13.0, this study examined 2390 primary glioblastoma samples from unique patients. Genomic alterations in 566 cancer-related genes were assessed using targeted next-generation sequencing panels from 3 large cancer institutes. The patient cohort included 112 Asians, 67 Blacks, and 2211 Whites. Statistical significance of associations between genomic alterations and race was evaluated using the chi-squared test, with the Benjamini-Hochberg method applied to control for multiple testing adjustments. RESULTS: Significant racial differences were observed in the frequency of genomic alterations. Asians exhibited a higher frequency of TP53 alterations (52.68%, P < 0.001), Blacks showed more frequent alterations in NRAS (7.46%, P < 0.001), MTOR (10.45%, P = 0.039), and TET2 (8.96%, P = 0.039), and Whites had a higher occurrence of PTEN alterations (48.67%, P = 0.045). Additionally, Black patients had an elevated rate of RET deletions (14.29%, P < 0.001). CONCLUSIONS: This study identifies significant racial disparities in the alteration frequencies of 6 key glioblastoma genes: NRAS, TP53, MTOR, TET2, PTEN, and RET. These findings underscore the need for racial considerations in glioblastoma treatment strategies and highlight potential avenues for targeted therapeutic interventions. Further research is needed to explore the clinical implications of these genomic disparities.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povo Asiático/genética , Biomarcadores Tumorais/genética , Negro ou Afro-Americano/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/etnologia , Estudos de Coortes , Proteínas de Ligação a DNA/genética , Genômica , Glioblastoma/genética , Glioblastoma/etnologia , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Mutação , Proteínas Proto-Oncogênicas/genética , PTEN Fosfo-Hidrolase/genética , Serina-Treonina Quinases TOR/genética , Proteína Supressora de Tumor p53/genética , Brancos/genéticaRESUMO
Glioblastoma (GBM), an aggressive form of brain cancer, has a higher incidence in non-Hispanics when compared to the US Hispanic population. Using data from RT-PCR analysis of 21 GBM tissue from Hispanic patients in Puerto Rico, we identified significant correlations in the gene expression of focal adhesion kinase and proline-rich tyrosine kinase (PTK2 and PTK2B) with NGFR (nerve growth factor receptor), PDGFRB (platelet-derived growth factor receptor B), EGFR (epithelial growth factor receptor), and CXCR1 (C-X-C motif chemokine receptor 1). This study further explores these correlations found in gene expression while accounting for sex and ethnicity. Statistically significant (p < 0.05) correlations with an r value > ±0.7 were subsequently contrasted with mRNA expression data acquired from cBioPortal for 323 GBM specimens. Significant correlations in Puerto Rican male patients were found between PTK2 and PTK2B, NGFR, PDGFRB, EGFR, and CXCR1, which did not arise in non-Hispanic male patient data. The data for Puerto Rican female patients showed correlations in PTK2 with PTK2B, NGFR, PDGFRB, and EGFR, all of which did not appear in the data for non-Hispanic female patients. The data acquired from cBioPortal for non-Puerto Rican Hispanic patients supported the correlations found in the Puerto Rican population for both sexes. Our findings reveal distinct correlations in gene expression patterns, particularly involving PTK2, PTK2B, NGFR, PDGFRB, and EGFR among Puerto Rican Hispanic patients when compared to non-Hispanic counterparts.
Assuntos
Neoplasias Encefálicas , Regulação Neoplásica da Expressão Gênica , Glioblastoma , Hispânico ou Latino , Transdução de Sinais , Humanos , Glioblastoma/genética , Glioblastoma/etnologia , Hispânico ou Latino/genética , Masculino , Feminino , Transdução de Sinais/genética , Porto Rico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/etnologia , Proteína-Tirosina Quinases de Adesão Focal/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Pessoa de Meia-Idade , Receptores ErbB/genética , Adulto , IdosoRESUMO
BACKGROUND: Brain metastases were rare in esophageal cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER) database, the present study investigated the incidence, risk and prognostic factors of brain metastases in esophageal cancer patients. METHODS: Retrieving esophageal cancer patients diagnosed between 2010 and 2018 from the SEER database, univariable and multivariable logistic and cox regression models were used to investigate the risk factors for brain metastases development and prognosis, respectively. The brain metastases predicting nomogram was constructed, evaluated and validated. The overall survival (OS) of patients with brain metastases was analyzed by Kaplan-Meier method. RESULTS: A total of 34,107 eligible esophageal cancer patients were included and 618 of them were diagnosed with brain metastases (1.8%). The median survival of the brain metastatic esophageal cancer patients was 5 (95% CI: 5-7) months. The presence of bone metastases and lung metastases were the homogeneously associated factors for the development and prognosis of brain metastases in esophageal cancer patients. Patients younger than 65 years, American Indian/Alaska Native race (vs. White), overlapping lesion (vs. Upper third), esophageal adenocarcinoma histology subtype, higher N stage, and liver metastases were positively associated with brain metastases occurrence. The calibration curve, ROC curve, and C-index exhibited good performance of the nomogram for predicting brain metastases. CONCLUSIONS: Homogeneous and heterogeneous factors were found for the development and prognosis of brain metastases in esophageal cancer patients. The nomogram had good calibration and discrimination for predicting brain metastases.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Esofágicas/patologia , Nomogramas , Programa de SEER , Adenocarcinoma/secundário , Idoso , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/mortalidade , Intervalos de Confiança , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/secundário , Modelos Logísticos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVE: To investigate racial disparities in 30-day postoperative outcomes of craniotomy for glioma resection. METHODS: 2006-2019 American College of Surgeons' National Surgical Quality Improvement Program files were queried for all patients who underwent a craniotomy for a supratentorial glioma resection. Racial disparities in preoperative variables were studied between the demographic cohorts of Asian, African Americans, Hispanics, and Caucasian. Fisher exact tests were used to examine association of preoperative variables with race. Multivariable logistic regression models, adjusted for all preoperative variables associated with race, were used to determine the odds ratios of postoperative outcomes for each demographic cohort in comparison with Caucasian patients. RESULTS: A total of 12,544 patients were identified: 4% Asian, 5% African American, 7% Hispanic, and 85% Caucasian. African American patients had significantly higher adjusted odds than Caucasian patients of major adverse cardiovascular events (adjusted odds ratio [aOR]: 1.827, 95% confidence interval [CI]: 1.155-2.891, P = 0.01), pulmonary events (aOR: 1.683, 95% CI: 1.145-2.473, P = 0.008), and urinary tract infection (aOR: 2.016, 95% CI: 1.221-3.327, P = 0.006). Asian patients had significantly higher odds than Caucasian patients of requiring a transfusion (aOR: 2.094, 95% CI: 1.343-3.266, P = 0.001). All demographic cohorts had higher odds of having an extended length of stay than Caucasian patients. CONCLUSIONS: African American patients who undergo a craniotomy for glioma resection have almost twice the odds of Caucasian patients of having a postoperative major cardiovascular complication, pulmonary complication, or urinary tract infection. All minority groups have higher odds of an extended length of stay as compared with Caucasian patients.
Assuntos
Neoplasias Encefálicas/etnologia , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/tendências , Complicações Pós-Operatórias/etnologia , Cuidados Pré-Operatórios/tendências , Grupos Raciais/etnologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/cirurgia , Craniotomia/efeitos adversos , Craniotomia/tendências , Feminino , Mortalidade Hospitalar/etnologia , Mortalidade Hospitalar/tendências , Humanos , Masculino , Complicações Pós-Operatórias/diagnósticoRESUMO
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 (â¼6,700 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.
Assuntos
Aeroportos , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/metabolismo , Exposição Ambiental , Meningioma/etiologia , Meningioma/metabolismo , Material Particulado , Negro ou Afro-Americano , Idoso , Encéfalo/patologia , Neoplasias Encefálicas/etnologia , Estudos de Coortes , Sistemas Computacionais , Etnicidade , Feminino , Humanos , Los Angeles , Masculino , Neoplasias Meníngeas/etnologia , Neoplasias Meníngeas/etiologia , Neoplasias Meníngeas/metabolismo , Meningioma/etnologia , Pessoa de Meia-Idade , Bulbo Olfatório/fisiologia , Estudos Prospectivos , Risco , Fatores de Risco , Estados UnidosRESUMO
Folate (vitamin B9) is found in some water-soluble foods or as a synthetic form of folic acid and is involved in many essential biochemical processes. Dietary folate is converted into tetrahydrofolate, a vital methyl donor for most methylation reactions, including DNA methylation. 5,10-methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate metabolism pathway that converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which produces a methyl donor for the remethylation of homocysteine to methionine. MTHFR polymorphisms result in reduced enzyme activity and altered levels of DNA methylation and synthesis. MTHFR polymorphisms have been linked to increased risks of several pathologies, including cancer. Breast cancer, gliomas and gastric cancer are highly heterogeneous and aggressive diseases associated with high mortality rates. The impact of MTHFR polymorphisms on these tumors remains controversial in the literature. This review discusses the relationship between the MTHFR C677T and A1298C polymorphisms and the increased risk of breast cancer, gliomas, and gastric cancer. Additionally, we highlight the relevance of ethnic and dietary aspects of population-based studies and histological stratification of highly heterogeneous tumors. Finally, this review discusses these aspects as potential factors responsible for the controversial literature concerning MTHFR polymorphisms.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias da Mama/genética , Glioma/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/metabolismo , Neoplasias da Mama/etnologia , Neoplasias da Mama/metabolismo , Metilação de DNA , Feminino , Ácido Fólico/metabolismo , Predisposição Genética para Doença , Glioma/etnologia , Glioma/metabolismo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/metabolismoRESUMO
Epidemiology provides an avenue for deciphering disease pathogenesis. By determining incidence across socioeconomic and demographic variables in the context of benign cerebral meningiomas (BCM), epidemiologic data may aid in elucidating and addressing healthcare inequalities. To investigate BCM incidence (per 100,000) with respect to sex, age, income, residence, and race/ethnicity, we queried the largest United States (US) administrative dataset (1997-2016), the National (Nationwide) Inpatient Sample (NIS), which surveys 20% of US discharges. Annual national BCM incidence was 5.01. Females had an incidence of 6.78, higher (p = 0.0000038) than males at 3.14. Amongst age groups incidence varied (p = 1.65 × 10-11) and was highest amongst those 65-84 (16.71) and 85+ (18.32). Individuals with middle/high income had an incidence of 5.27, higher (p = 0.024) than the 4.91 of low income patients. Depending on whether patients lived in urban, suburban, or rural communities, incidence varied (χ2 = 8.22, p = 0.016) as follows, respectively: 5.23; 4.96; 5.51. Amongst race/ethnicity (p = 8.15 × 10-14), incidence for Whites, Blacks, Asian/Pacific Islanders, Hispanics, and Native Americans were as follows, respectively: 5.05; 4.59; 4.22; 2.99; 0.55. In the US, BCM annual incidence exhibited disparities amongst socioeconomic and demographic subsets. Disproportionately, incidence was greatest for patients who were White, Black, female, 65 and older, and middle/high income.
Assuntos
Neoplasias Encefálicas/economia , Etnicidade , Disparidades em Assistência à Saúde/economia , Renda , Neoplasias Meníngeas/economia , Meningioma/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/terapia , Feminino , Humanos , Masculino , Neoplasias Meníngeas/etnologia , Neoplasias Meníngeas/terapia , Meningioma/etnologia , Meningioma/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/etnologia , Adulto JovemRESUMO
BACKGROUND: Despite improvements in overall survival for pediatric cancers, treatment disparities remain for racial/ethnic minorities compared to non-Hispanic Whites; however, the impact of race on treatment outcomes for pediatric brain and central nervous system (CNS) tumors in the United States is not well known. METHODS: We included 8713 children aged 0-19 years with newly diagnosed primary brain and CNS tumors between 2000 and 2015 from the Census Tract-level SES and Rurality Database developed by Surveillance, Epidemiology, and End Results (SEER) Program. We used chi-square tests to assess differences in sociodemographic, cancer, and treatment characteristics by race/ethnicity and Kaplan-Meier curves and Cox proportional hazards models to examine differences in 10-year survival, adjusting for these characteristics. RESULTS: Among 8713 patients, 56.75% were non-Hispanic White, 9.59% non-Hispanic Black, 25.46% Hispanic, and 8.19% from "other" racial/ethnic groups. Median unadjusted survival for all pediatric brain tumors was 53 months, but varied significantly by race/ethnicity with a median survival of 62 months for non-Hispanic Whites, 41 months for non-Hispanic Blacks, and 40 months for Hispanic and other. Multivariable analyses demonstrated minority racial groups still had significantly higher hazard of death than non-Hispanic Whites; Hispanic (adjusted hazard ratio [aHR] 1.25 [1.18-1.31]); non-Hispanic Black (aHR 1.12 [1.04-1.21]); other (aHR 1.22 [1.12-1.32]). Results were consistent when stratified by tumor histology. CONCLUSION: We identified disparities in survival among racial/ethnic minorities with pediatric brain and CNS tumors, with Hispanic patients having the highest risk of mortality. Eliminating these disparities requires commitment toward promoting heath equity and personalized cancer treatment.
Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias do Sistema Nervoso Central/mortalidade , Etnicidade/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Adolescente , Adulto , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/terapia , Neoplasias do Sistema Nervoso Central/etnologia , Neoplasias do Sistema Nervoso Central/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Programa de SEER , Fatores Socioeconômicos , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto JovemRESUMO
PURPOSE: Although 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. METHODS: A 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. RESULTS: During 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. CONCLUSIONS: Compared 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.
Assuntos
Estatura , Índice de Massa Corporal , Neoplasias Encefálicas/etnologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Japão/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
Glioblastoma (GBM) is the most malignant primary brain tumor in adults with substantial genomic alterations. The median survival is approximately 14.6 months, despite aggressive therapeutic intervention, which comprised of surgical resection, radiotherapy, and chemotherapy. Recent studies on cancer genomic have revealed crucial insights into dynamic molecular subgroups within GBM, which govern distinct clinical response and sensitivity of each individual to therapy. In the present study, we analyzed genomic composition of primary GBMs between two ethnic groups [IRCR (Institute of Refractory Cancer Research), and TCGA (The Cancer Genome Atlats)] to explore genomic and molecular features that constitute malignant behavior of glioblastoma based on distinct ethnicity. We identified enrichments of MAPK and p53 pathways in IRCR patients, while aberrant activation of Receptor Tyrosine Kinases (RTKs) were predominant in TCGA cohort. We also discovered differential clinical prognosis between two groups and explored essential features that present such diversity.
Assuntos
Povo Asiático/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/genética , Glioblastoma/etnologia , Glioblastoma/genética , População Branca/genética , Adulto , Idoso , Neoplasias Encefálicas/cirurgia , Bases de Dados de Ácidos Nucleicos , Feminino , Perfilação da Expressão Gênica , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , RNA-Seq , República da Coreia/epidemiologia , Transcriptoma , Sequenciamento do ExomaRESUMO
BACKGROUND: cranial X radiation therapy was the standard of care for treating dermatological conditions until the 1960s, when its association to cancer and particularly high rates of brain tumors was discovered. This study examines associations found between incidence of brain tumor and ethnicity. METHODS: This study analyzed two cohorts who underwent examination at age 17 and were followed by linkage to the national cancer registry. The first cohort included 376,336 participants born in 1948-1959 (when treatment with cranial X radiation was standard care for treating tinea capitis), and the second 474,923 participants born in 1960-1971. RESULTS: In the first cohort, ethnicity was strongly associated with the incidence of brain tumor (BT), with higher incidence observed among patients with origins in North Africa or the Middle East. This effect was ablated in the second cohort, and a significant decrease in the rate of meningiomas was noted. CONCLUSION: The association of brain tumor with ethnicity was present only during the period when treatment with cranial X radiation was the standard of care for TC in Israel, therefore it is most likely that radiation exposure was a confounding factor, and that ethnic susceptibility for brain cancer was not causative in these cohorts.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnologia , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/etnologia , África do Norte/etnologia , Idoso , Estudos de Coortes , Etnicidade , Feminino , Seguimentos , Humanos , Israel/etnologia , Masculino , Pessoa de Meia-Idade , Oriente Médio/etnologia , Sistema de Registros , Tinha do Couro Cabeludo/etnologia , Tinha do Couro Cabeludo/radioterapiaRESUMO
BACKGROUND: Survivors of pediatric brain tumor are at risk for adaptive difficulties. The present study examined adaptive functioning in a multiethnic sample of survivors accounting for socioeconomic status, and whether demographic, diagnostic, and/or treatment-related variables predict adaptive outcomes. METHOD: Participants included a multiethnic sample of survivors (58 Caucasian, 34 Hispanic, and 22 other non-Caucasian; M age = 14.05 years, SD = 4.33) who were approximately seven years post-treatment. Parents rated adaptive functioning and provided demographic information. Diagnostic and treatment-related information was abstracted from the electronic medical record. RESULTS: Parent ratings of adaptive functioning were similar across Caucasian, Hispanic, and other non-Caucasian survivors covarying for family income and primary caregiver education, both of which served as proxies for socioeconomic status. All ethnic groups were rated lower than the normative mean in overall adaptive functioning as well as the specific domains of conceptual, social, and practical skills. Demographic, diagnostic, and treatment-related variables were differentially associated with adaptive functioning in survivors of pediatric brain tumor, though socioeconomic status emerged as a strong significant predictor of adaptive functioning domains. CONCLUSIONS: Adaptive outcomes do not differ as a function of ethnicity after accounting for primary caregiver education and family income. Racial and ethnic minorities may be at increased risk for poorer outcomes given their overrepresentation at lower income levels. Assessing demographic and treatment-related variables early on may be helpful in identifying children likely to develop adaptive difficulties.
Assuntos
Neoplasias Encefálicas/etnologia , Sobreviventes de Câncer , Hispânico ou Latino , Classe Social , População Branca , Adolescente , Adulto , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
Glioma is the most common malignant primary brain tumors with poor prognosis. Genome wide association studies (GWAS) of glioma in populations with Western European ancestry were completed in the US and UK. However, our previous results strongly suggest the genetic heterogeneity could be important in glioma risk. To systematically investigate glioma risk-associated variants in Chinese population, we performed a multistage GWAS of glioma in the Han Chinese population, with a total of 3,097 glioma cases and 4,362 controls. In addition to confirming two associations reported in other ancestry groups, this study identified one new risk-associated locus for glioma on chromosome 12p11.23 (rs10842893, pmeta = 2.33x10-12, STK38L) as well as a promising association at 15q15-21.1 (rs4774756, pmeta = 6.12x10-8, RAB27A) in 3,097 glioma cases and 4,362 controls. Our findings demonstrate two novel association between the glioma risk region marked by variant rs10842893 and rs4774756) and glioma risk. These findings may advance the understanding of genetic susceptibility to glioma.
Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Proteínas rab27 de Ligação ao GTP/genética , Neoplasias Encefálicas/etnologia , Estudos de Casos e Controles , China/etnologia , Europa (Continente)/etnologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Glioma/etnologia , Humanos , MasculinoAssuntos
Neoplasias Encefálicas , Glioma , Adulto , Neoplasias Encefálicas/etnologia , Glioma/terapia , HumanosRESUMO
Importance: Glioma is the most commonly occurring malignant brain tumor in the United States, and its incidence varies by age, sex, and race or ethnicity. Survival after brain tumor diagnosis has been shown to vary by these factors. Objective: To quantify the differences in incidence and survival rates of glioma in adults by race or ethnicity. Design, Setting, and Participants: This population-based study obtained incidence data from the Central Brain Tumor Registry of the United States and survival data from Surveillance, Epidemiology, and End Results registries, covering the period January 1, 2000, to December 31, 2014. Average annual age-adjusted incidence rates with 95% CIs were generated by glioma histologic groups, race, Hispanic ethnicity, sex, and age groups. One-year and 5-year relative survival rates were generated by glioma histologic groups, race, Hispanic ethnicity, and insurance status. The analysis included 244â¯808 patients with glioma diagnosed in adults aged 18 years or older. Data were collected from January 1, 2000, to December 31, 2014. Data analysis took place from December 11, 2017, to January 31, 2018. Results: Overall, 244â¯808 patients with glioma were analyzed. Of these, 150â¯631 (61.5%) were glioblastomas, 46â¯002 (18.8%) were non-glioblastoma astrocytomas, 26â¯068 (10.7%) were oligodendroglial tumors, 8816 (3.6%) were ependymomas, and 13â¯291 (5.4%) were other glioma diagnoses in adults. The data set included 137 733 males (56.3%) and 107 075 (43.7%) females. There were 204 580 non-Hispanic whites (83.6%), 17 321 Hispanic whites (7.08%), 14 566 blacks (6.0%), 1070 American Indians or Alaska Natives (0.4%), and 5947 Asians or Pacific Islanders (2.4%). Incidences of glioblastoma, non-glioblastoma astrocytoma, and oligodendroglial tumors were higher among non-Hispanic whites than among Hispanic whites (30% lower overall), blacks (52% lower overall), American Indians or Alaska Natives (58% lower overall), or Asians or Pacific Islanders (52% lower overall). Most tumors were more common in males than in females across all race or ethnicity groups, with the great difference in glioblastoma where the incidence was 60% higher overall in males. Most tumors (193â¯329 [79.9%]) occurred in those aged 45 years or older, with differences in incidence by race or ethnicity appearing in all age groups. Survival after diagnosis of glioma of different subtypes was generally comparable among Hispanic whites, blacks, and Asians or Pacific Islanders but was lower among non-Hispanic whites for many tumor types, including glioblastoma, irrespective of treatment type. Conclusions and Relevance: Incidence of glioma and 1-year and 5-year survival rates after diagnosis vary significantly by race or ethnicity, with non-Hispanic whites having higher incidence and lower survival rates compared with individuals of other racial or ethnic groups. These findings can inform future discovery of risk factors and reveal unaddressed health disparities.
Assuntos
Neoplasias Encefálicas/etnologia , Glioma/etnologia , Vigilância da População/métodos , Programa de SEER/estatística & dados numéricos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Feminino , Glioma/diagnóstico , Glioma/epidemiologia , Disparidades nos Níveis de Saúde , Hispânico ou Latino/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: While survival in overall pediatric malignancy has improved during recent decades, brain/central nervous system (CNS) tumors has not demonstrated comparable survival advantage. Incidence and mortality data in this malignancy continue to illustrate race and sex differences; however, there are few data in the pediatric setting. This study sought to characterize brain/CNS tumors by socio-demographic and assess racial and sex variances in both cumulative incidence and mortality. METHODS: A retrospective cohort design with Surveillance, Epidemiology and End Results (SEER) 1973-2014 was used for the assessment of children aged < 1-19 years diagnosed with brain/CNS tumors. The age-adjusted incidence rates were used for temporal trends, percent change, and annual percent change. We utilized binomial regression model to determine the exposure effect of race and sex on cancer mortality, adjusting for potential confounders. RESULTS: Childhood brain/CNS tumor cumulative incidence (CmI) continues to rise in annual percent change, and mortality varied by race, sex, and year of diagnosis. The CmI was highest among whites, intermediate among blacks, and lowest among Asians, as well as lower in females relative to that in males. Compared to whites, blacks were 21% more likely to die from brain/CNS tumors [risk ratio (RR) 1.21, 95% confidence interval (C.I.) 1.13-1.28], while males were 4% more likely to die relative to females (RR 1.04, 95% C.I. 1.00-1.08). After controlling for age, sex, and tumor grade, racial disparities persisted, with 16% increased risk of dying among blacks relative to whites [adjusted risk ratio 1.16, (99% C.I.) 1.08-1.25, p < 0.001]. CONCLUSION: The cumulative incidence of brain/CNS malignancy is higher among whites relative to that in blacks; however, blacks experienced survival disadvantage even after adjustment for potential tumor prognostic and predisposing factors.
Assuntos
Neoplasias Encefálicas/etnologia , Etnicidade/estatística & dados numéricos , Mortalidade/etnologia , Adolescente , Negro ou Afro-Americano , Asiático , Neoplasias Encefálicas/mortalidade , Neoplasias do Sistema Nervoso Central/etnologia , Neoplasias do Sistema Nervoso Central/mortalidade , Criança , Pré-Escolar , Feminino , Disparidades nos Níveis de Saúde , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Programa de SEER , Distribuição por Sexo , População BrancaRESUMO
This is a single centre study in mainland China aiming to evaluate the reliability, validity and responsiveness of the Chinese version of EORTC QLQ-BN20, designed by The European Organization for Research and Treatment of Cancer Quality of Life Group to evaluate the life quality of patients with brain tumour, cancer or metastases. One hundred and eighty-eight patients with primary or secondary brain cancer from Hunan Provincial Tumor Hospital during September 2013 to June 2014 completed the Chinese EORTC QLQ-C30/BN20 questionnaires developed by translation, back translation and cultural adaptation. Results were statistically analysed using SPSS17.0. The internal consistency (Cronbach's α coefficient) was between .753 and .869, the correlation coefficients among items and its own dimension were bigger than .4, and all items had a better correlation with its own dimension. The Spearman was used to analyse the correlation of each dimension between EORTC QLQ-BN20 and EORTC QLQ-C30, and the result showed that individual dimensions were moderately correlated, other dimensions were weakly correlated. In conclusion, the Chinese version of EORTC QLQ BN20 questionnaire had great relevance, reliability, convergent validity and discriminant validity. It provides a valuable tool for the assessment of health-related quality of life in clinical studies of Chinese patients with primary or secondary brain cancer.
Assuntos
Neoplasias Encefálicas/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Adolescente , Adulto , Idoso , Povo Asiático/etnologia , Neoplasias Encefálicas/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Adulto JovemRESUMO
The objective of this study is to shed light on racial disparities among Hispanic and African American adult brain tumor patients treated at Harbor-UCLA Medical Center compared to the general populations of Los Angeles County (LAC) and Torrance, California (CA). A retrospective review of patients admitted to the neurosurgery service at Harbor-UCLA Medical Center during years 2006 through 2010 was performed. Government census data was queried and pertinent national statistics were retrieved. Brain tumor patients at Harbor-UCLA were compared to the general populations of LAC and Torrance. A total of 271 patients were included in the study. The mean age was 46.9â¯years. Hispanics comprised the majority of neurosurgical patients (nâ¯=â¯151, 55.7%), followed by African Americans (nâ¯=â¯35, 12.9%). A greater percentage of Hispanic patients were treated at Harbor-UCLA relative to the general Hispanic populations of LAC and Torrance (pâ¯<â¯.001). A greater percentage of African American patients were treated at Harbor-UCLA relative to the general African American populations of LAC and Torrance (pâ¯=â¯.035 and pâ¯<â¯.001, respectively). Our data revealed significant racial disparities amid the Harbor-UCLA Hispanic and African American patient populations compared to the general Angeleno populations of LAC and Torrance.
Assuntos
Centros Médicos Acadêmicos/tendências , Negro ou Afro-Americano/etnologia , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/cirurgia , Disparidades em Assistência à Saúde/tendências , Hispânico ou Latino , Centros Médicos Acadêmicos/normas , Adulto , Idoso , Feminino , Disparidades em Assistência à Saúde/normas , Humanos , Los Angeles/etnologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This case-control study aimed to investigate the association between PHLDB1 rs498872 polymorphism and the risk of glioma in a Chinese Han population. A total of 210 patients and 235 controls were enrolled in this study. The CT genotype and TT genotype were significantly associated with the risk of glioma (OR=1.48, 95%CI 1.00-2.19, P=0.05 and OR=2.40, 95%CI 1.06-4.10, P=0.03), respectively. In addition, T allele of PHLDB1 rs498872 polymorphism was significantly associated with an increased risk of glioma (OR=1.58, 95%CI 1.08-2.29, P=0.02). We also found that PHLDB1 rs498872 polymorphism was not associated with histology and tumor grade of glioma. In conclusion, this study found that PHLDB1 rs498872 polymorphism was significantly associated with glioma risk in Chinese Han population.
Assuntos
Neoplasias Encefálicas/genética , Predisposição Genética para Doença , Glioma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Povo Asiático , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Frequência do Gene , Glioma/diagnóstico , Glioma/etnologia , Glioma/patologia , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Razão de Chances , Fatores de RiscoRESUMO
BACKGROUND: Racial disparities exist in health care, frequently resulting in unfavorable outcomes for minority patients. Here, we use guided machine learning (ML) ensembles to model the impact of race on discharge disposition and length of stay (LOS) after brain tumor surgery from the Healthcare Cost and Utilization Project National Inpatient Sample. METHODS: We performed a retrospective cohort study of 41,222 patients who underwent craniotomies for brain tumors from 2002 to 2011 and were registered in the National Inpatient Sample. Twenty-six ML algorithms were trained on prehospitalization variables to predict non-home discharge and extended LOS (>7 days) after brain tumor resection, and the most predictive algorithms combined to create ensemble models. Partial dependence analysis was performed to measure the independent impact of race on the ensembles. RESULTS: The guided ML ensembles predicted non-home disposition (area under the curve, 0.796) and extended LOS (area under the curve, 0.824) with good discrimination. Partial dependence analysis showed that black race increases the risk of non-home discharge and extended LOS over white race by 6.9% and 6.5%, respectively. Other, nonblack race increases the risk of extended LOS over white race by 6.0%. The impact of race on these outcomes is not seen when analyzing the general inpatient or general operative population. CONCLUSIONS: Minority race independently increases the risk of extended LOS and black race increases the risk of non-home discharge in patients undergoing brain tumor resection, a finding not mimicked in the general inpatient or operative population. Recognition of the influence of race on discharge and LOS could generate interventions that may improve outcomes in this population.