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.

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.

Age-specific cancer incidence rates increase through the oldest age groups.

BACKGROUND: In the United States, from 2005 to 2009, nearly 8% of all cancers diagnosed and 15% of cancer deaths occurred in individuals aged 85 years and older (85+ age group). With the aging of the U.S. population, an analysis of incidence of cancer in the elderly population may provide information for clinical care and resource allocation. MATERIALS AND METHODS: Previously reported data were retrieved from the Surveillance Epidemiology and End Results (SEER) 18 Registry for years 2000 to 2010 and Central Brain Tumor Registry of the United States (CBTRUS) for years 2004 to 2008. Cancers included invasive cases only, except for nonmalignant meningiomas, and rates were per 100,000. RESULTS: The age-specific cancer incidence rate (IR) increases with age until a decrease in the 85+ age group. IR for all cancers combined for this age group was 2,317 per 100,000. Statistically, males had significantly higher IR compared with females (3,194 versus 1,911 [P≤0.0001]). Blacks had an IR similar to whites (2,255 versus 2,340 [P=0.12]). Despite a drop in the overall IR in this oldest age group, IR for certain cancers continued to increase. Among these cancers, gastrointestinal cancers like colorectal, pancreatic and stomach had the highest incidence and mortality rates. CONCLUSIONS: This study contributes to measuring cancer burden in the oldest old population. In certain cancers, including meningiomas, the IR continues to rise with advancing age. Management of cancer in elderly is challenging and screening persons in the 85+ age group for frailty very thoroughly may help guide decisions of palliative versus aggressive therapies.

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.

Investigating ocular dimensions in African Americans with long anterior zonules.

PURPOSE: To investigate ocular dimensions in African Americans with the long anterior zonule (LAZ) trait. METHODS: A total of 61 African American LAZ subjects and 61 age-matched, race-matched, and sex-matched controls were compared with respect to central corneal thickness, central corneal curvature, axial length (AL), and subjective refraction. RESULTS: LAZ right eyes had a mean SR=+1.75±1.82 D and were 1.58 D (95% confidence interval, 0.83-2.31 D, P<0.0001) more hyperopic on average when compared with the control right eyes. LAZ right eyes also had an AL that was 0.69 mm (95% confidence interval, 0.34-1.04 mm, P<0.001) shorter on average than control right eyes. Similar results were found for left eyes. No differences were found with respect to central corneal curvature and central corneal thickness (P>0.05). CONCLUSIONS: In this data set, LAZ eyes tended to be more hyperopic and had ALs that were shorter than control eyes, characteristics that are consistent with elevated risk for angle-closure glaucoma.

Description of selected characteristics of familial glioma patients - results from the Gliogene Consortium.

BACKGROUND: While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part of the Gliogene Consortium. METHODS: Families with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires. FINDINGS: The study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (±standard deviation [SD]) diagnosis age was 49.4 (±18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at <40y, and in 12% both were diagnosed under 40y of age. Most of these families (76%) had at least one grade IV glioblastoma multiforme (GBM), and in 32% both cases were grade IV gliomas. The most common glioma subtype was GBM (55%), followed by anaplastic astrocytoma (10%) and oligodendroglioma (8%). Individuals with grades I-II were on average 17y younger than those with grades III-IV. INTERPRETATION: Familial glioma cases are similar to sporadic cases in terms of gender distribution, age, morphology and grade. Most familial gliomas appear to comprise clusters of two cases suggesting low penetrance, and that the risk of developing additional gliomas is probably low. These results should be useful in the counselling and clinical management of individuals with a family history of glioma.

A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma.

BACKGROUND: We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma. METHODS: First, we fit segregation models by formulating the likelihood for a person to have a bivariate phenotype, affection status and age of onset, along with other covariates, and from these we estimate population trait allele frequencies and penetrance parameters as a function of age (N = 281 multiplex glioma pedigrees). Second, the best fitting models are used as trait models in multipoint linkage analysis (N = 74 informative multiplex glioma pedigrees). To correct for ascertainment, a prevalence constraint is used in the likelihood of the segregation models for all 281 pedigrees. Then the trait allele frequencies are reestimated for the pedigree founders of the subset of 74 pedigrees chosen for linkage analysis. RESULTS: Using the best-fitting segregation models in model-based multipoint linkage analysis, we identified 2 separate peaks on chromosome 17; the first agreed with a region identified by Shete and colleagues who used model-free affected-only linkage analysis, but with a narrowed peak: and the second agreed with a second region they found but had a larger maximum log of the odds (LOD). CONCLUSIONS: Our approach was able to narrow the linkage peak previously published for glioma. IMPACT: We provide a practical solution to model-based linkage analysis for disease affection status with variable age of onset for the kinds of pedigree data often collected for linkage analysis.

Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data.

Few population estimates of brain metastasis in the United States are available, prompting this study. Our objective was to estimate the expected number of metastatic brain tumors that would subsequently develop among incident cancer cases for 1 diagnosis year in the United States. Incidence proportions for primary cancer sites known to develop brain metastasis were applied to United States cancer incidence data for 2007 that were retrieved from accessible data sets through Centers for Disease Control and Prevention (CDC Wonder) and Surveillance, Epidemiology, and End Results (SEER) Program Web sites. Incidence proportions were identified for cancer sites, reflecting 80% of all cancers. It was conservatively estimated that almost 70 000 new brain metastases would occur over the remaining lifetime of individuals who received a diagnosis in 2007 of primary invasive cancer in the United States. That is, 6% of newly diagnosed cases of cancer during 2007 would be expected to develop brain metastasis as a progression of their original cancer diagnosis; the most frequent sites for metastases being lung and bronchus and breast cancers. The estimated numbers of brain metastasis will be expected to be higher among white individuals, female individuals, and older age groups. Changing patterns in the occurrence of primary cancers, trends in populations at risk, effectiveness of treatments on survival, and access to those treatments will influence the extent of brain tumor metastasis at the population level. These findings provide insight on the patterns of brain tumor metastasis and the future burden of this condition in the United States.

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.

Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries.

Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has been considered to be higher in East Asia than in the United States. This study estimates the incidence of CNS GCTs in Japan and the United States, investigates gender discrepancies in each country, and describes treatment outcomes. Data on primary CNS GCTs from 4 databases were utilized: population-based malignant incidence data from (1) the Japan Cancer Surveillance Research Group (2004-2006; 14 registries), malignant and nonmalignant incidence data from (2) the Surveillance, Epidemiology, and End Results Program (2004-2008; 17 registries), and hospital-based observed survival data from (3) the Brain Tumor Registry of Japan (1984-2000) and (4) the US National Cancer Data Base (1990-2003). Incidence rates per 100 000 for malignant GCTs were not statistically significantly different between Japan (males = 0.143, females = 0.046) and the United States (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1, respectively). In general, 5-year survival estimates were high: over 75% for all GCTs, and over 81% for germinomas, regardless of the type of treatment in either Japan or the United States. The incidence of primary GCTs is similar between Japan and the United States and has the same gender-based patterns by location. High rates of survival were observed in both countries.

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.

Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium.

Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial 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.

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.

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.

Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system.

BACKGROUND: The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year's report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. METHODS: Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC's National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992-2007 for incidence; 1975-2007 for mortality) trends and short-term fixed interval (1998-2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980-2007; data on nonmalignant tumors were available for 2004-2007. All statistical tests were two-sided. RESULTS: Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P < .05) in women, but not in men, because of a recent increase in prostate cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 2003-2007, more than a decade after decreasing in men. During 2004-2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987-2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. CONCLUSIONS: The decrease in cancer incidence and mortality reflects progress in cancer prevention, early detection, and treatment. However, major challenges remain, including increasing incidence rates and continued low survival for some cancers. Malignant and nonmalignant brain tumors demonstrate differing patterns of occurrence by sex, age, and race, and exhibit considerable biologic diversity. Inclusion of nonmalignant brain tumors in cancer registries provides a fuller assessment of disease burden and medical resource needs associated with these unique tumors.

Medical diagnostic radiation exposures and risk of gliomas.

High-dose ionizing radiation is an established risk factor for glioma, but it remains unknown whether moderate- and low-dose radiation increase glioma risk. In this analysis, we assessed the evidence that self-reported exposures to diagnostic ionizing radiation, including computerized tomography (CT) scans, is associated with increased risk of adult glioma. While no independent association was observed for CT scans alone (3+ scans compared to none P = 0.08 and 1-2 scans compared to none P = 0.68), our findings suggest an increased risk of adult gliomas with cumulative exposure to three or more CT scans to the head and neck region (OR = 1.97, 95% CI: 0.92-4.23) limited to those who reported a family history of cancer: the P value for the interaction between having three or more CT scans and family history of cancer was 0.08. The stratum-specific adjusted OR for those with family history of cancer was more than three times that for the sub-group without family history of cancer. While there is some potential for symptom-related bias, one might expect this to be present for all diagnostic procedures rather than specific to one procedure. The interaction between CT scans and glioma with family history of cancer supports the biological plausibility of our findings, because similar results have been found for breast cancer and radiation. This observational data will increase awareness about potential risks associated with CT scans and the need to minimize the use of unnecessary examinations.

Assessment of type of allergy and antihistamine use in the development of glioma.

BACKGROUND: Allergies have been associated with decreased risk of glioma; but, associations between duration and timing of allergies, and antihistamine use and glioma risk have been less consistent. The objective was to investigate this association by analyzing types, number, years since diagnosis, and age at diagnosis of allergies, and information on antihistamine usage, including type, duration, and frequency of exposure. METHODS: Self-report data on medically diagnosed allergies and antihistamine use were obtained for 419 glioma cases and 612 hospital-based controls from Duke University and NorthShore University HealthSystem. RESULTS: High- and low-grade glioma cases were statistically significantly less likely to report any allergy than controls (OR = 0.66, 95% CI: 0.49-0.87 and OR = 0.44, 95% CI: 0.25-0.76, respectively). The number of types of allergies (seasonal, medication, pet, food, and other) was inversely associated with glioma risk in a dose-response manner (P value for trend < 0.05). Age at diagnosis and years since diagnosis of allergies were not associated with glioma risk. Oral antihistamine use was statistically significantly inversely associated with glioma risk, but when stratified by allergy status, remained significant only for those with high-grade glioma and no medically diagnosed allergy. CONCLUSIONS: All types of allergies appear to be protective with reduced risk for those with more types of allergies. Antihistamine use, other than in relationship with allergy status, may not influence glioma risk. IMPACT: A comprehensive study of allergies and antihistamine use using standardized questions and biological markers will be essential to further delineate the biological mechanism that may be involved in brain tumor development.

Risk factors for oligodendroglial tumors: a pooled international study.

Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.