Descriptive epidemiology of malignant and nonmalignant primary spinal cord, spinal meninges, and cauda equina tumors, United States, 2004-2007.

BACKGROUND: Primary tumors of the spinal cord, spinal meninges, and cauda equina are relatively rare, and a paucity of population-based data exist on tumors in these sites. This study intends to augment the current literature by examining incidence of these tumors on a national level. METHODS: Data from central cancer registries in the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) programs for 2004-2007 (covering 99.2% of US population) and 1999-2007 (covering 89.4% of US population) were analyzed. Analyses for diagnosis years 2004-2007 included cases of malignant and nonmalignant primary spinal cord, spinal meninges, and cauda equina tumors. Descriptive statistics including estimated age-adjusted incidence rates standardized to the 2000 US standard population were conducted for both malignant and nonmalignant primary spinal tumors from cases diagnosed during 2004-2007 as well as trend analyses on malignant cases of primary spinal tumors (n = 5103) for cases diagnosed during 1999-2007 using SEER Stat 6.6.2 software. RESULTS: There were 2576 cases of malignant primary spinal tumors and 9136 cases of nonmalignant primary spinal tumors in 2004-2007. The incidence of malignant and nonmalignant primary spinal tumors combined differed by age, sex, race, and ethnicity. Results of trend analyses indicated that malignant primary spinal tumors have been stable throughout the 1999-2007 period. CONCLUSIONS: This large population-based study adds new insights into the descriptive epidemiology of primary spinal cord, spinal meninges, and cauda equina tumors by providing in-depth analyses of the incidence of these tumors on a national level.

Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma.

The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P(trend) <1.0 × 10(-8)). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.

Improved survival time trends for glioblastoma using the SEER 17 population-based registries.

The EORTC/NCIC 22981/26981 study demonstrated an improvement in median overall survival (OS) from 12.1 to 14.6 months in patients with glioblastoma (GBM) who received temozolomide with post-operative radiotherapy (RT). The current study was performed to determine if those results translated into a survival benefit in a population-based cohort. Patients diagnosed between 2000 and 2006 with a GBM who underwent surgery and post-operative RT were selected from the Surveillance, Epidemiology and End Results database. Patients were grouped into time periods: 2000-2001, 2002-2003, 2004 and 2005-2006 (which represented those treated after the EORTC/NCIC trial presentation in 2004). Relative survival (RS) was estimated by the Kaplan-Meier method, and Cox multivariable regression modeling was used to estimate proportional hazard ratios (HR). Over time, there was improvement in the median and 2-year RS of 12 months and 15% for 2000-2001, 13 months and 19% for 2002-2003, 14 months and 24% for 2004, and 15 months and 26% for 2005-2006 (P < 0.0001 compared to 2000-2001 and 2002-2003; P = 0.07 compared to 2004). The estimated adjusted HR showed that patients diagnosed in 2005-2006 had significantly improved survival when compared to patients diagnosed in 2000-2001 (HR = 0.648, 95% CI 0.604-0.696). The median and 2 year RS of 15 months and 26% in 2005-2006 was similar to the median and 2 year OS of 14.6 months and 26% seen in the EORTC/NCIC phase III study. These results are encouraging and suggest that the current treatment of glioblastoma nationwide is now associated with an improved survival compared to previous time cohorts.

Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking.

Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility. Data from 855 high-grade glioma cases and 1,160 controls from 4 geographic regions of the United States during 1997-2008 were analyzed for interactions between allergy and smoking histories and inherited variants in 5 established glioma risk regions: 5p15.3 (TERT), 8q24.21 (CCDC26/MLZE), 9p21.3 (CDKN2B), 11q23.3 (PHLDB1/DDX6), and 20q13.3 (RTEL1). The inverse relation between allergy and glioma was stronger among those who did not (odds ratio(allergy-glioma) = 0.40, 95% confidence interval: 0.28, 0.58) versus those who did (odds ratio(allergy-glioma) = 0.76, 95% confidence interval: 0.59, 0.97; P(interaction) = 0.02) carry the 9p21.3 risk allele. However, the inverse association with allergy was stronger among those who carried (odds ratio(allergy-glioma) = 0.44, 95% confidence interval: 0.29, 0.68) versus those who did not carry (odds ratio(allergy-glioma) = 0.68, 95% confidence interval: 0.54, 0.86) the 20q13.3 glioma risk allele, but this interaction was not statistically significant (P = 0.14). No relation was observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk of smoking history with any of the risk alleles. The authors' observations are consistent with a recent report that the inherited glioma risk variants in chromosome regions 9p21.3 and 20q13.3 may modify the inverse association of allergy and glioma.

Update on meningiomas.

Although meningiomas are the most common tumor in the central nervous system, their incidence, epidemiology, and clinical outcomes have historically been poorly defined. This has been attributed to their benign course, difficulty obtaining histologic diagnosis, and lack of uniform database registration. Their clinical behavior can range from a silent incidentaloma to a lethal tumor. Projections of an aging population should raise medical awareness of an expectant rise in the incidence of meningiomas. This disease increases with advancing age, has a female predilection, and exposure to ionizing radiation is associated with a higher risk for disease development. There have been minimal advances in treatment, except in radiation therapy. Although no U.S. Food and Drug Administration-approved systemic therapy exists, there are treatment options that include hydroxyurea and sandostatin. Currently, no molecularly targeted therapy has provided clinical benefit, although recurring molecular alterations are present and novel therapies are being investigated.

Conditional survival of all primary brain tumor patients by age, behavior, and histology.

BACKGROUND: Survival statistics commonly reflect survival from the time of diagnosis but do not take into account survival already achieved after a diagnosis. The objective of this study was to provide conditional survival estimates for brain tumor patients as a more accurate measure of survival for those who have already survived for a specified amount of time after diagnosis. METHODS: Data on primary malignant and nonmalignant brain tumor cases diagnosed from 1985-2005 from selected SEER state cancer registries were obtained. Relative survival up to 15 years postdiagnosis and varying relative conditional survival rates were computed using the life-table method. RESULTS: The overall 1-year relative survival estimate derived from time of diagnosis was 67.8% compared to the 6-month relative conditional survival rate of 85.7% for 6-month survivors (the probability of surviving to 1 year given survival to 6 months). The 10-year overall relative survival rate was 49.5% from time of diagnosis compared to the 8-year relative conditional survival rate of 79.2% for 2-year survivors. Conditional survival estimates and standard survival estimates varied by histology, behavior, and age at diagnosis. The 5-year relative survival estimate derived from time of diagnosis for glioblastoma was 3.6% compared to the 3-year relative conditional survival rate of 36.4% for 2-year survivors. For most nonmalignant tumors, the difference between relative survival and the corresponding conditional survival estimates were minimal. Older age groups had greater numeric gains in survival but lower conditional survival estimates than other age groups. Similar findings were seen for other conditional survival intervals. CONCLUSIONS: Conditional survival is a useful disease surveillance measure for clinicians and brain tumor survivors to provide them with better 'real-time' estimates and hope.

Association between body mass index and mortality in patients with glioblastoma mutliforme.

PURPOSE: To examine the association between obesity and survival in patients with glioblastoma mutliforme (GBM) METHODS: Using a prospective design, 1,259 patients with previously untreated GBM were recruited between 1991 and 2008. Height and weight were self-reported or abstracted from medical records at study entry and used to calculate body mass index (BMI) [weight (kg)/[height (m)](2). Cox proportional models were used to estimate the risk of death associated with BMI as a continuous variable or categorized using established criteria (normal weight, 18.5-24.9 kg/m(2); overweight, 25.0-29.9 kg/m(2); obese, ≥ 30.0 kg/m(2)). RESULTS: Median follow-up was 40 months, and 1,069 (85%) deaths were observed during this period. For all patients, minimal adjusted analyses indicated no significant association between BMI treated as a continuous variable and survival. Compared with patients with a BMI 18.5-24.9 kg/m(2), the minimally adjusted HR for overall survival was 1.08 (95% CI, 0.94-1.24) for a BMI 25-29.9 kg/m(2) and 1.08 (95% CI, 0.91-28) for a BMI ≥ 30.0 kg/m(2). After additional adjustment for adjuvant therapy, the HR for those with a BMI of 25.0-29.9 kg/m(2) was 1.14 (95% CI, 0.99-1.32) and 1.09 (95% CI, 0.91-1.30) for those with a BMI ≥ 30.0 kg/m(2). No significant interactions were revealed for BMI and any demographic variables. CONCLUSION: BMI was not associated with survival in newly diagnosed and previously untreated patients with GBM. Further research investigating the prognostic significance of alternative, quantitative measures of body habitus, and functional performance are required.

Descriptive epidemiology of selected olfactory tumors.

Olfactory tumors, especially olfactory neuroblastomas (ON) and carcinomas with neuroendocrine differentiation (CND), are extremely rare, and little descriptive epidemiologic information is available. The objective of this study was to more fully describe selected olfactory tumors using a large population-based cancer incidence database. The Surveillance, Epidemiology and End Results (SEER) 9 registries limited-use data were reviewed from 1973 to 2006 for selected nasal cavity (C30.0) and accessory sinus (C31.0-31.9) tumors. Frequencies, incidence rates, and relative survival rates were estimated using SEER*Stat, v6.5.2. The majority of cases were squamous cell carcinoma (SCC), while the incidence of ON was greater than CND. For ON, the incidence was highest in the 60-79 year age group, while for SCC, the incidence was highest in the 80+ year age group. For CND, the incidence leveled off in the oldest age groups. Survival rates were highest for ON (>70% alive at 5 years after diagnosis) and poorest for CND (44% alive at 5 years). Adjuvant radiation therapy did not improve survival over surgery alone in ON. In SCC, survival was worse in patients who received adjuvant radiation compared to patients who had surgery alone. Our analysis confirms some previously published information, and adds new information about the incidence and demographics of ON and CND. In addition, our analysis documents the lack of benefit of adjuvant radiation in ON. It is not feasible to conduct prospective trials in patients with these rare diseases, and the importance of registry data in learning about olfactory tumors is emphasized.

Association between glioma and history of allergies, asthma, and eczema: a case-control study with three groups of controls.

Because glioma etiology is largely unknown, the inverse association of glioma risk with atopic conditions is promising and deserves close scrutiny. We examined the association between a history of allergies, asthma, and eczema, and glioma risk using sibling, friend, and clinic-based controls. This analysis included 388 incident glioma cases and 80 sibling, 191 friend, and 177 clinic-based controls. Each subject's medical history was assessed via a Web-based or telephone survey. Odds ratios (OR) and their 95% confidence intervals (CI) for the associations with allergies, asthma, eczema, and the overall number of these conditions were calculated from conditional (for sibling and friend controls) and unconditional (for clinic-based controls) logistic models. Allergies were consistently inversely associated with the glioma: ORs were 0.53 (95% CI, 0.15-1.84), 0.54 (95% CI, 0.28-1.07), and 0.34 (95% CI, 0.23-0.50) with sibling, friend, and clinic-based controls, respectively. Asthma showed an inverse association only in the comparison with sibling controls (OR, 0.43; 95% CI, 0.19-1.00). Eczema showed an inverse association only in the comparison with friend controls (OR, 0.42; 95% CI, 0.15-1.18). The overall number of these conditions (ordinal score 0, 1, 2, 3) was inversely associated with glioma: The risk decreased 31% to 45% with each addition of an atopic condition. These estimates were the most stable when different control groups were considered. Comparing the prevalence of these conditions in the three control groups with published data, we note that clinic-based controls generally better approximate the prevalence data for population-based groups. These controls seem to present a reasonable choice for clinic-centered case-control studies.

A case for the worldwide collection of primary benign brain tumors.

BACKGROUND: Incidence data on malignant tumors are reported by the International Agency for Research on Cancer, with 189,485 new malignant brain tumors globally in 2002. However, collection and reporting of benign brain tumors are not universal. The objective here is to encourage the collection of primary benign brain tumors worldwide. METHODS: Worldwide numbers of primary benign brain tumors were estimated through published articles and cancer registry reports presenting directly or indirectly reported benign incidence rates or frequencies for regions or countries. RESULTS: An estimated 186,678 benign brain tumors were diagnosed worldwide in 2002. The estimated numbers of benign brain tumors were higher in females than males (105,918 vs. 80,759). Since many countries do not report primary benign brain tumors, the incidence rate estimates vary significantly by region. CONCLUSIONS: This is the first survey to assess worldwide numbers of benign brain tumors. Under-reporting, non-standardized collection, lack of age-adjustment, and other causes of the varying incidence rates must be considered. However, the estimated number of benign brain tumors approximately equals, and could exceed, the number of malignant brain tumors globally. Registration of primary benign brain histologies in different geographical areas and ethnicities could provide clues to the underlying causes of these tumors.

Human exposure to selected animal neurocarcinogens: a biomarker-based assessment and implications for brain tumor epidemiology.

This review is based on the proceedings from the Second Lebow Conference, held in Chicago in 2007. The conference concentrated on developing a framework for innovative studies in the epidemiology of environmental exposures, focusing specifically on the potential relationship with brain tumors. Researchers with different perspectives, including toxicology, pharmacokinetics, and epidemiological exposure assessment, exchanged information and ideas on the use of biomarkers of exposure in molecular epidemiology studies and summarized the current knowledge on methods and approaches for biomarker-based exposure assessment. This report presents the state of science regarding biomarker-based exposure assessment of the four most common neurocarcinogens: acrylamide, 1,3-butadiene, N-nitroso compounds, and polycyclic aromatic hydrocarbons. Importantly, these chemicals are also carcinogenic in other organs; therefore, this discussion is useful for environmental epidemiologists studying all cancer types.

The Impact of the Benign Brain Tumor Cancer Registries Amendment Act (Public Law 107-260) on Non-malignant Brain and Central Nervous System Tumor Incidence Trends.

The study objective was to investigate patterns of reported non-malignant brain and CNS tumor incidence over a time period encompassing 1997-2008 during which time the Benign Brain Tumor Cancer Registries Amendment Act (PL 107-260) was passed and implemented. Analyses of 75,350 incident non-malignant brain and CNS tumors from eleven population-based central registries revealed that there were statistically significant increases in the age-adjusted incidence rate for non-malignant tumors for those diagnosed prior to 2002 and over the time period from 2002 until 2005. However, no significant change in the age-adjusted incidence rate for non-malignant tumors was observed over the time period 2005 to 2008 indicating that the incidence from this time period may quantify the "true" incidence of non-malignant brain and CNS tumors in the United States.

Comparing the reliability of responses to telephone-administered versus self-administered Web-based surveys in a case-control study of adult malignant brain cancer.

INTRODUCTION: To determine whether a Web-based survey was an acceptable method of data collection for a clinic-based case-control study of adult brain cancer, the authors compared the reliability of paired responses to a main and resurvey for participants completing surveys by telephone (n=74) or self-administered on the Web (n=465) between 2003 and 2006. METHODS: Recruitment of cases was done at the Evanston Northwestern Healthcare Kellogg Cancer Care Center and the Duke University Medical Center Cancer Control division, and controls were friends and siblings of cases. Twenty-five variables were examined, including smoking, oral contraceptive and residential histories, water sources, meat preparation, fruit and vegetable consumption, and pesticide use. Weighted and simple kappa's were estimated for categorical and binary variables, respectively. RESULTS: The number of concordant paired responses was summed for use in linear regression. Respondents were 97% White and 85% had postsecondary education. Kappa's for individual questions ranged from 0.31 (duration of residence in a single family house) to 0.96 (ever smoked), with a median of 0.57 (95% confidence interval, 0.47-0.64). The median number of concordant responses was 16.2 (range, 5-22). Reliability was greater for controls than cases, Web-based versus telephone responders, females, and higher-income responders. Frequency of e-mail and Internet use was not associated with reliability. CONCLUSIONS: A self-administered, Web-based survey was a feasible and appropriate mode of interview in this study. The comparable reliability of Web compared with telephone responses suggest that Web-based self-interviews could be a cost-effective alternative to traditional modes of interview.

Issues of diagnostic review in brain tumor studies: from the Brain Tumor Epidemiology Consortium.

Epidemiologists routinely conduct centralized single pathology reviews to minimize interobserver diagnostic variability, but this practice does not facilitate the combination of studies across geographic regions and institutions where diagnostic practices differ. A meeting of neuropathologists and epidemiologists focused on brain tumor classification issues in the context of protocol needs for consortial studies (http://epi.grants.cancer.gov/btec/). It resulted in recommendations relevant to brain tumors and possibly other rare disease studies. Two categories of brain tumors have enough general agreement over time, across regions, and between individual pathologists that one can consider using existing diagnostic data without further review: glioblastomas and meningiomas (as long as uniform guidelines such as those provided by the WHO are used). Prospective studies of these tumors benefit from collection of pathology reports, at a minimum recording the pathology department and classification system used in the diagnosis. Other brain tumors, such as oligodendroglioma, are less distinct and require careful histopathologic review for consistent classification across study centers. Epidemiologic study protocols must consider the study specific aims, diagnostic changes that have taken place over time, and other issues unique to the type(s) of tumor being studied. As diagnostic changes are being made rapidly, there are no readily available answers on disease classification issues. It is essential that epidemiologists and neuropathologists collaborate to develop appropriate study designs and protocols for specific hypothesis and populations.

Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries.

The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor databases. Three different databases were used: Surveillance, Epidemiology, and End Results (SEER) database (1973-2001); Central Brain Tumor Registry of the United States (CBTRUS; 1997-2001); and National Cancer Data Base (NCDB; 1985-2003). Tumors were identified using the International Classification of Diseases for Oncology, third edition (ICD-O-3), site code C75.3, and categorized according to histology codes 9060-9085. Data were analyzed using SAS/STAT release 8.2, SEER*Stat version 5.2, and SPSS version 13.0 software. A total of 1,467 cases of malignant pineal germ-cell tumors were identified: 1,159 from NCDB, 196 from SEER, and 112 from CBTRUS. All three databases showed a male predominance for pineal germ-cell tumors (>90%), and >72% of patients were Caucasian. The peak number of cases occurred in the 10- to 14-year age group in the CBTRUS data and in the 15- to 19-year age group in the SEER and NCDB data, and declined significantly thereafter. The majority of tumors (73%-86%) were germinomas, and patients with germinomas had the highest survival rate (>79% at 5 years). Most patients were treated with surgical resection and radiation therapy or with radiation therapy alone. The number of patients included in this study exceeds that of any study published to date. The proportions of malignant pineal germ-cell tumors and intracranial germ-cell tumors are in range with previous studies. Survival rates for malignant pineal germ-cell tumors are lower than results from recent treatment trials for intracranial germ-cell tumors, and patients that received radiation therapy in the treatment plan either with surgery or alone survived the longest.

Time trends in oligodendroglial and astrocytic tumor incidence.

BACKGROUND: We hypothesized that the incidences of oligodendrogliomas, anaplastic oligodendrogliomas, and mixed gliomas have significantly increased from the early 1990 s forward, while the incidences of anaplastic and grade II astrocytic tumors have significantly decreased. METHODS: Data for the years 1973-2004 from the Surveillance, Epidemiology and End Results (SEER) public-use data and for 1985-2004 from six collaborating registries of the Central Brain Tumor Registry of the US (CBTRUS) were obtained. SEER*Stat was used to estimate age-adjusted incidence trends and annual percent change (APC) for selected histologies. Joinpoint regression was used to identify sharp changes in incidences occurring over time. RESULTS: Using CBTRUS data, the incidences (per 100,000 person-years) of oligodendrogliomas (APC = 4.7), mixed gliomas (APC = 3.9) and anaplastic oligodendrogliomas (APC = 12.5) have all increased over time, while the incidences of astrocytoma not otherwise specified (APC = -8.1) and fibrillary astrocytoma (APC = -2.1) have decreased. Restricting the analyses to later years (1992-2004) using SEER data shows the incidence of oligodendrogliomas leveling off (APC = 0.5), while joinpoint analyses demonstrate a decreasing trend after 1998. CONCLUSIONS: This study has demonstrated that increases in oligodendroglial tumor incidence correspond to decreases in astrocytic tumor incidence over the same time period. Minimizing misclassification of glial tumors will be essential for accurately assessing incidence, survival, and mortality rates, as well as for identifying homogeneous subgroups for epidemiologic and treatment studies.

Application of mutagen sensitivity assay in a glioma case-control study.

Few risk factors for glioma have been identified other than ionizing radiation. The alkylating agent acrylamide is a compound found in both occupational and the general environment and identified as one of the forty known or suspected neurocarcinogens in animal models. The mutagen sensitivity assay (MSA) has been used to indirectly show reduced DNA repair capacity upon exposure to ionizing radiation in those with glioma compared to controls. In this study, MSA was used to assess its applicability to a glioma case-control study and to test the hypothesis that subjects with glioma may have lower DNA repair capacity after exposure to selected potential human neurocarcinogens (i.e. acrylamide), compared to controls. Approximately 50 case and 50 control subjects were identified from a clinic-based study that investigated environmental risk factors for glioma, who completed an exposure survey, and had frozen immortalized lymphocytes available. A total of 50 metaphase spreads were read and reported for each participant. The association of case-control status with MSA for acrylamide, i.e. breaks per spread, was examined by multivariable logistic regression models. The mean number of breaks per slide was similar between hospital-based controls and cases. In addition, case-control status or exposure categories were not associated with the number of breaks per spread. Although the MSA has been shown as a useful molecular epidemiology tool for identifying individuals at higher risk for cancer, our data do not support the hypothesis that glioma patients have reduced DNA repair capacity in response to exposure to acrylamide. Further research is needed before the MSA is utilized in large-scale epidemiological investigations of alkylating agents.

GLIOGENE an International Consortium to Understand Familial Glioma.

Evidence for familial aggregation of glioma has been documented in both case-control and cohort studies and occurs apart from the well-described rare inherited genetic syndromes involving glioma: neurofibromatosis type 1 and 2, tuberous sclerosis, Turcot's syndrome, and Li-Fraumeni syndrome. Nonsyndromic glioma families have been studied but no genes have been identified in the two published linkage studies of familial glioma probably due to the small number of families. Because glioma is a rare but devastating cancer, and a family history of glioma has been observed in approximately 5% of the cases, we initiated an international consortium to identify glioma families not affected by syndromes to better understand the inherited factors related to this disease. The international consortium GLIOGENE is an acronym for "glioma gene" and includes 15 research groups in North America, Europe, and Israel to study familial glioma. The overarching goal is to characterize genes in glioma families using a genome-wide single-nucleotide polymorphism approach and conducting linkage analysis to identify new genomic regions or loci that could harbor genes important for gliomagenesis. Here, we review the rationale for studying familial glioma and our proposed strategy for the GLIOGENE study.

Seasonal variation in incidence of pediatric medulloblastoma in the United States, 1995-2001.

BACKGROUND/AIMS: Brain tumors are the second most common pediatric malignancy. The literature suggests that one of the most common subtypes of malignant childhood brain tumor, medulloblastoma, has some seasonal variation in incidence by month of birth. METHODS: Data from cases in the Central Brain Tumor Registry of the United States, including primary brain tumor cases diagnosed in children (0-19 years) between the years 1995 and 2001 from 13 state cancer registries, were analyzed to determine whether there was seasonal variation. Analyses were performed using Edwards' test for sinusoidal variation, which uses case frequencies per month, and tests whether frequencies follow a sine function over 12 months. RESULTS: Seasonal variation in incidence by month of birth was highly statistically significant for medulloblastoma, not otherwise specified (NOS) (p = 0.016), with the peak occurring in October. Medulloblastoma, NOS also demonstrated seasonal variation in incidence by month of birth in children aged 5-19 (p = 0.041), especially females aged 5-19 (p = 0.034), with the peak in October. There were no significant results for brain tumors overall, or for the other most common pediatric tumor subtypes (pilocytic astrocytoma, other astrocytoma, and ependymoma). CONCLUSION: These preliminary results indicate seasonal variation unique to medulloblastoma incidence by month of birth and may provide evidence for an environmental exposure etiology, though further studies are needed to explore specific hypotheses.

Temporal trends in incidence of primary brain tumors in the United States, 1985-1999.

A number of reports have indicated an increasing incidence of primary brain tumors over the past few decades. The purpose of this study was to describe incidence rate trends in a population-based series of newly diagnosed primary nonmalignant and malignant brain and other CNS tumors, contributing five additional years to previously published incidence trends. Data for the years 1985 through 1999 from six collaborating state cancer registries of the Central Brain Tumor Registry of the United States were used to determine incidence trends in the broad age groups 0-19, 20-64, and >or=65 years, overall and for selected histologies. Multiplicative Poisson regression was used to express trends as average annual percent change (AAPC). Joinpoint regression was used to identify sharp changes in incidence occurring over this period. Overall, incidence increased modestly (AAPC, 1.1; 95% CI, 0.8-1.4). When brain lymphomas were excluded, this increase remained statistically significant. A sharp change in incidence of brain lymphomas from increasing to decreasing over time was identified. Specific histologies that were increasing included anaplastic astrocytomas in individuals aged >or=65 years, microscopically confirmed gliomas in both adult age groups, and microscopically confirmed glioma, not otherwise specified (NOS), in children. Increases that were not specific to any population subgroup were seen for oligodendrogliomas, ependymomas, meningiomas, and nerve sheath tumors. Decreases were noted for astrocytoma, NOS, nonmicroscopically confirmed gliomas, and pituitary tumors. Improvements in diagnosis and classification are likely reflected in the decreasing trends in unspecified glioma subgroups and the accompanying increasing trends in more specific glioma subgroups. However, increases in meningiomas and nerve sheath tumors deserve further attention.