Influence of county-level geographic/ancestral origin on glioma incidence and outcomes in US Hispanics.

BACKGROUND: Glioma incidence is 25% lower in Hispanics than White non-Hispanics. The US Hispanic population is diverse, and registry-based analyses may mask incidence differences associated with geographic/ancestral origins. METHODS: County-level glioma incidence data in Hispanics were retrieved from the Central Brain Tumor Registry of the United States. American Community Survey data were used to determine the county-level proportion of the Hispanic population of Mexican/Central American and Caribbean origins. Age-adjusted incidence rate ratios and incidence rate ratios (IRRs) quantified the glioma incidence differences across groups. State-level estimates of admixture in Hispanics were obtained from published 23andMe data. RESULTS: Compared to predominantly Caribbean-origin counties, predominantly Mexican/Central American-origin counties had lower age-adjusted risks of glioma (IRR = 0.83; P < 0.0001), glioblastoma (IRR = 0.86; P < 0.0001), diffuse/anaplastic astrocytoma (IRR = 0.78; P < 0.0001), oligodendroglioma (IRR = 0.82; P < 0.0001), ependymoma (IRR = 0.88; P = 0.012), and pilocytic astrocytoma (IRR = 0.76; P < 0.0001). Associations were consistent in children and adults and using more granular geographic regions. Despite having lower glioma incidence, Hispanic glioblastoma patients from predominantly Mexican/Central American-origin counties had poorer survival than Hispanics living in predominantly Caribbean-origin counties. Incidence and survival differences could be partially explained by state-level estimates of European admixture in Hispanics with European admixture associated with higher incidence and improved survival. CONCLUSIONS: Glioma incidence and outcomes differ in association with the geographic origins of Hispanic communities, with counties of predominantly Mexican/Central American origin at significantly reduced risk and those of Caribbean origin at comparatively greater risk. Although typically classified as a single ethnic group, appreciating the cultural, socioeconomic, and genetic diversity of Hispanics can advance cancer disparities research.

Association between telomerase reverse transcriptase rs2736100 polymorphism and risk of glioma.

BACKGROUND: Epidemiological studies have been conducted to investigate the association of telomerase reverse transcriptase (TERT) rs2736100 polymorphism with glioma risk. The aim of the present study was to evaluate the association of TERT rs2736100 polymorphism with glioma risk using a meta-analysis approach. MATERIALS AND METHODS: All eligible studies were identified through a search of PubMed, EMBASE, China National Knowledge Infrastructure, Database of Chinese Scientific and Technical Periodicals, and China Biology Medical literature database before January 2014. The association between the TERT rs2736100 polymorphism and glioma risk was estimated by odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of nine case-control studies including 9411 cases and 13,708 controls were eventually collected. Overall, we found that TERT rs2736100 polymorphism was significantly associated with the risk of glioma (OR = 1.29, 95% CI 1.24-1.34, P < 0.001). In the subgroup analysis based on ethnicity, the significant association was found in Caucasians (OR = 1.29, 95% CI 1.24-1.34, P < 0.001). In subgroup analyses by histology, the associations were significant in glioblastoma (OR = 1.45, 95% CI 1.32-1.60, P < 0.001), astrocytoma (OR = 1.41, 95% CI 1.26-1.58, P < 0.001), and oligodendroglioma (OR = 1.20, 95% CI 1.05-1.37, P = 0.008). CONCLUSIONS: Taken together, these data suggested that TERT rs2736100 polymorphism may contribute to glioma susceptibility.

RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population.

Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case-control study from Xi'an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

Chromosome DNA imbalances in human astrocytic tumors: a comparative genomic hybridization study of 63 Chinese patients.

Astrocytic tumors are the most frequent primary brain neoplasms. They are clinically characterized by wide variations in histology. Analysis of chromosome DNA imbalance may help to advance diagnosis, grading, and classification, and to determine appropriate therapeutic approaches for tumors of astrocytic lineages. Comparative genomic hybridization (CGH) provides comprehensive information about chromosome DNA aberrations, and is an important technique for evaluating the differences at genomic levels among the same or different grade tumors. In this study, 63 astrocytic tumors of Chinese patients were screened by CGH, and the relationship between their chromosome DNA imbalances and the histopathological classification, grading, and clinical features was analyzed. Most tumors showed genomic copy aberrations detected by CGH. The most frequent abnormalities were regional gains in chromosome 1q and 7p; regional losses in chromosome 1p, 2q, 4q, 6p, 10q, 12q, 15q, 19q, and 22q were also frequently observed. The gain of 1q and the loss of 15q were relevant to the histological types and grades of WHO classification. The losses of 4q and 10q correlated with age in the group of anaplastic astrocytoma, which was unreported in the literature. This study confirmed that chromosomal aberrations, such as +1q, -4q, -10q, +7p, and -15q possibly contributed to the pathogenesis of these tumors. Our data was the first report on the chromosomal aberrations of astrocytic tumors of Chinese patients.

Association of EGFR c.2073A>T polymorphism with decreased risk of diffusely infiltrating astrocytoma in a Brazilian case-control study.

Epidermal growth factor receptor (EGFR) gene overexpression has been implicated in the development of many types of tumors, including glioblastomas, the most frequent diffusely infiltrating astrocytomas. However, little is known about the influence of the polymorphisms of EGFR on EGFR production and/or activity, possibly modulating the susceptibility to astrocytomas. This study aimed to examine the association of two EGFR promoter polymorphisms (c.-191C>A and c.-216G>T) and the c.2073A>T polymorphism located in exon 16 with susceptibility to astrocytomas, EGFR gene expression and survival in a case-control study of 193 astrocytoma patients and 200 cancer-free controls. We found that the variant TT genotype of the EGFR c.2073A>T polymorphism was associated with a significantly decreased risk of astrocytoma when compared with the AA genotype [sex- and age-adjusted odds ratio 0.51, 95% confidence interval 0.26-0.98]. No association of the two promoter EGFR polymorphisms (or combinations of these polymorphisms) and risk of astrocytomas, EGFR expression or survival was found. Our findings suggest that modulation of the EGFR c.2073A>T polymorphism could play a role in future therapeutic approaches to astrocytoma.

Genome-wide oligonucleotide microarray analysis of gene-expression profiles of Taiwanese patients with anaplastic astrocytoma and glioblastoma multiforme.

This study investigated the relationship between gene expression and disease based on the expression profiles of tissue-specific genes, with the aim of discovering the candidate genes associated with disease risk as diagnostic markers. The gene-expression profiles of approximately 20,000 genes from 4 anaplastic astrocytomas (AAs), 7 glioblastoma multiformes (GBMs), and 1 nontumor brain (NB) were analyzed by in situ-synthesized 60-mer oligonucleotide microarray. The signal intensity of each feature was measured by laser scanner, and gene expression was quantified as the tumor/NB intensity ratio. Gene expression was defined as having increased or decreased when the ratio was >or=1.5 or

Pediatric brain tumors in non-Hispanics, Hispanics, African Americans and Asians: differences in survival after diagnosis.

BACKGROUND: Racial differences in survival for children with brain tumors have not been well studied, particularly in Hispanics and Asians. The objective of this study was to assess racial differences in survival of children with brain tumors, focusing on Hispanics, African Americans and Asians compared to Non-Hispanics. METHODS: Subjects identified through the SEER Program were 2799 children, < or =19 years old at diagnosis, newly diagnosed between 1973 and 1996 with primary, malignant brain tumors. Chi-square tests were used to evaluate prognostic variables by race. Kaplan-Meier models and Cox proportional hazards models were used to assess racial differences in overall survival and in survival by histological type of tumor. RESULTS: The distribution histological type of tumor varied significantly by race. Overall survival was similar for Hispanics, African Americans, Asians compared to Non-Hispanics, although trends of increased risk of death for the minority groups were noted when stratifying by histological type of tumor. CONCLUSIONS: Racial differences in survival could exist by histological type of tumor, but further work is necessary for a more complete understanding of these differences.

Racial differences in survival after diagnosis with primary malignant brain tumor.

BACKGROUND: Previous studies have shown that the overall incidence of primary malignant brain tumor is greatest in Caucasians, although survival is better in African Americans. The objective of this study was to examine racial differences in survival after diagnosis with primary malignant brain tumor in a population-based sample of patients while adjusting for prognostic variables that differ by race. METHODS: The authors analyzed 21,493 patients (20,493 Caucasians and 1000 African Americans) who were diagnosed with primary malignant brain tumors from 1973 to 1997 (with follow-up through 1999) from the population-based Surveillance, Epidemiology, and End Results (SEER) Program. Chi-square tests were used to determine statistical significance of prognostic variables and race (using two-sided P values). Kaplan-Meier and Cox proportional hazards models were used to assess survival differences by race. RESULTS: The univariable model for race showed no survival difference by race. The multivariable model demonstrated that African American patients were at a 13% increased risk of death from any cause compared with Caucasian patients. The racial difference was explained further by an interaction between race and surgery type in which there was an increased risk of death for African American patients who underwent subtotal resections or surgery not otherwise specified compared with Caucasian patients who underwent the same procedures. CONCLUSIONS: There was a significant difference in the risk of death due to any cause for Caucasian patients and African American patients who were diagnosed with first primary brain tumors.

Birth characteristics and brain cancers in young children.

BACKGROUND: High birthweight is a potential risk factor for childhood brain tumours, particularly astrocytomas. We investigated several birth characteristics in relationship to brain cancers in young children. METHODS: We obtained 849 invasive central nervous system (CNS) cancer cases, ages 0-4 years, from California's population-based cancer registry for 1988-1997. We matched 746 (88%) of these cases to a California live birth certificate. We randomly selected two control birth certificates for each case, matched on date of birth and gender. We used conditional logistic regression to obtain odds ratios (OR) and 95% CI. The birth characteristics examined included birthweight, gestational age, race, parental age, and parental education. RESULTS: Analysing all CNS tumours combined, we found that children of other racial/ ethnic groups had OR below one compared with non-Hispanic white children. When adjusted for gestational age, race/ethnicity, and mother's place of birth, the OR for high birthweight (>/=4000 g) was 1.05 (95% CI: 0.79-1.38) compared with children with birthweights of 2500-3999 g. For astrocytomas (313 cases), the adjusted OR for high birthweight was 1.40 (95% CI: 0.90-2.18). When parental education was included in the model (available for only a subset of the birth years), the adjusted OR was 1.71 (95% CI: 1.01-2.90). High birthweight did not appear to be a risk factor for primitive neuroectodermal tumours (PNET). CONCLUSIONS: We found high birthweight associated with increased risk of astrocytomas, but not PNET, in young children.

Racial differences in the incidence of gliomas: a retrospective study from Memphis, Tennessee.

This study records the incidence of glioblastoma multiforme, astrocytoma and oligodendroglioma in the white and Black patients in the Memphis Statistical Metropolitan Area (MSMA) during a 10.5-year period from 1 January 1984 through 30 June 1994. During this time, only six hospitals performed craniotomy and computer tomography (CT) scanning was routine in each of the hospitals. A total of 824 histologically confirmed first diagnoses were made at these six area hospitals. Based on the zip code listed as the home address, we determined patient's locale and identified 373 patients (232 glioblastoma multiforme, 106 astrocytomas and 35 oligodendroglioma) who resided in the area during the study interval. There were 50 black and 323 white patients. The background population for the area was obtained from the US Census Bureau's statistics for the year 1990. These statistics indicated that 40.5% of the population identified themselves as black and 57.9% as white. Age adjusted incidence rates were 1.550 (p < 0.001) for other astrocytomas, and 0.106 and 0.461 (p = 0.003) in the black and white populations, respectively. There was no significant difference in survival between the two populations. This study confirms a significant disparity in incidence rates for the three most common gliomas between the black and white populations and this disparity is higher than predicted by previous reports.

[Primary brain tumors].

In our retrospective analysis of 305 patients with primary brain tumors, treated and followed at Rambam Medical Center between 1983-1990, 56% were males; mean age was 43; 47% were Ashkenazi Jews, 22% Sephardi Jews, 22% Arabs and 9% were Jews of unspecified origin. 3-year actuarial survival for all patients was 33.5%, Arabs 51%, Sephardi Jews 40%, Ashkenazi Jews 20%; for those younger than 20, it was 57%, and older than 20, 26%. Diagnoses were: astrocytoma grades I-II, 68%; astrocytoma grade III, 24%; glioblastoma multiforme, 5.5%; medulloblastoma 73%; ependymoma, 75%; oligodendroglioma, 85%; meningioma, 100%; pituitary adenoma, 100%. Survival probability of those with glioblastoma multiforme treated by combined surgery and radiotherapy was superior to that of those treated by surgery alone. In low-grade astrocytoma there was no difference in survival probability between those with combined therapy and those treated by surgery alone. Survival when the diagnosis was based on imaging studies alone without histological confirmation of malignancy, was similar to that of those with glioblastoma: only 3.0% at 3 years. Prognostic factors identified by univariate analysis were histology, age of patient and ethnic origin, and type of treatment.

Descriptive epidemiology of primary tumors of the spinal cord and spinal meninges in Los Angeles County, 1972-1985.

This report presents data on the distribution of 462 primary tumors of the spinal cord and spinal meninges (both benign and malignant) diagnosed among residents of Los Angeles County from 1972 to 1985. Incidence rates of gliomas, meningiomas, nerve sheath tumors, and all histologic types combined are presented for specific age, sex, and ethnic groups. The highest rates are seen for meningiomas in women (age-adjusted rate 3/million/year compared to 1/million/year for the other two histologic types in women and for each of the three types in men). Proportional incidence ratios for spinal tumors are elevated among men and women born in Eastern Europe and among Jewish residents of Los Angeles County. The incidence rates appear not to relate to the social class.

Tumours of the central nervous system in Chinese in Hong Kong: a histological review.

One hundred and sixty-eight cases of tumours of the central nervous system (CNS) from Chinese patients in Hong Kong were reviewed histologically as well as by the immunoperoxidase techniques in equivocal cases. Detailed comparisons were made between this series and previously published series on CNS tumours in Chinese, in other Asians and in Caucasians. The percentage of gliomas was low, and the average age of patients with high grade astrocytomas was low. Meningiomas were relatively common tumours and microcystic meningiomas were a common histological subtype. The percentages of vascular malformations and haemangioblastomas were also higher than those recorded in the West. The difference in incidence in gliomas and vascular malformations between this series and previous reports from mainland China was attributed to a possible difference between southern and northern Chinese.