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We established the nationwide, population-based incidence of oligodendroglioma in Denmark during 59 years of monitoring and compared the overall survival of patients with oligodendroglial tumors during the periods 1943-1977 and 1978-2002. On the basis of reports in the Danish Cancer Registry, 1,304 cases of oligodendroglioma were included in the study. We calculated sex- and age-specific incidence rates in 5-year age intervals and for 5-year calendar periods. Overall survival was estimated by the Kaplan-Meier method. In the period 1943-2002, the incidence rate of oligodendroglioma was less than 1 case per 100,000 person-years, but varied somewhat when viewed across isolated periods. Comparison of the incidence rate before and after the introduction of CT scanning did not reveal a significant difference in the incidence rate. The median survival increased from 1.4 years (95% confidence interval [CI], 1.0-1.6) to 3.4 years (95% CI, 2.6-4.2) during the period of study. The overall incidence of oligodendroglioma showed a relatively stable pattern over nearly 60 years of monitoring. Overall survival improved significantly during the study period, which could partly be due to improved diagnostic methods and treatment options.

Female sex hormones have previously been suggested as possible risk factors for brain tumors, but published studies have reported conflicting results. We conducted a population-based case-control study of glioma (n=626) and meningioma (n=906) cases and randomly selected controls stratified on age and geographic region (n=1,774) in Denmark, Finland, Norway, Sweden, and the United Kingdom. Unconditional logistic regression was used to estimate odds ratios (OR) for glioma and meningioma in relation to reproductive factors. A decreased glioma risk was associated with ever-pregnancy compared with never-pregnancy [OR, 0.8; 95% confidence interval (95% CI), 0.6-1.0]. Meningioma risk among women ages <50 years was increased in relation to number of pregnancies leading to a live birth (OR, 1.8; 95% CI: 1.1-2.8 for giving birth to 3 children compared with nulliparous women; P(trend) among parous women=0.01). This relation was not found for older women. Breast-feeding among parous women increased the glioma risk (OR, 2.2; 95% CI, 1.3-3.9 for breast-feeding 36 months or more compared with breast-feeding 3 months or less). Menopausal status and age at menopause were not associated with meningioma or glioma risk. Our findings imply that reproductive hormones may influence the occurrence of meningioma and glioma.

Several single nucleotide polymorphisms (SNPs) affecting DNA repair capacity and modifying cancer susceptibility have been described. We evaluated the association of SNPs Arg194Trp, Arg280His, and Arg399Gln in the X-ray cross-complementing group 1 (XRCC1) and Thr241Met in the X-ray cross-complementing group 3 (XRCC3) DNA repair genes with the risk of brain tumors. The Caucasian study population consisted of 701 glioma (including 320 glioblastoma) cases, 524 meningioma cases, and 1,560 controls in a prospective population-based case-control study conducted in Denmark, Finland, Sweden, and the UK. The studied SNPs were not significantly associated with the risk of brain tumors. The highest odds ratios (ORs) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma (OR = 1.32; 95% confidence interval, CI, 0.97-1.81), glioblastoma (OR = 1.48; 95% CI, 0.98-2.24), and meningioma (OR = 1.34; 95% CI, 0.96-1.86). However, in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors: Among others, carriers of both homozygous variant genotypes, i.e., XRCC1 Gln399Gln and XRCC3 Met241Met, were associated with a three-fold increased risk of glioma (OR = 3.18; 95% CI, 1.26-8.04) and meningioma (OR = 2.99; 95% CI, 1.16-7.72). In conclusion, no significant association with brain tumors was found for any of the polymorphisms, when examined one by one. Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors.

Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) influences the risk of primary brain tumors, we genotyped 1,005 glioma cases, 631 meningioma cases, and 1,101 controls for the MTHFR C677A and A1298C, MTRR A66G, and MTR A2756G variants. MTHFR C677T-A1298C diplotypes were associated with risk of meningioma (P = 0.002) and glioma (P = 0.02); risks were increased with genotypes associated with reduced MTHFR activity. The highest risk of meningioma was associated with heterozygosity for both MTHFR variants [odds ratio (OR), 2.11; 95% confidence interval (95% CI), 1.42-3.12]. The corresponding OR for glioma was 1.23 (95% CI, 0.91-1.66). A significant association between risk of meningioma and homozygosity for MTRR 66G was also observed (OR, 1.41; 95% CI, 1.02-1.94). Our findings provide support for the role of folate metabolism in the development of primary brain tumors. In particular, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk.

Much of the variation in inherited risk of glioma is likely to be explained by combinations of common low risk variants. The established relationship between glioma risk and exposure to ionizing radiation led us to examine whether variants in the DNA repair genes contribute to disease susceptibility. We evaluated 1127 haplotype-tagging single-nucleotide polymorphisms (SNPs) supplemented with 388 putative functional SNPs to capture most of the common variation in 136 DNA repair genes, in five unique case-control series from four different countries (1013 cases, 1016 controls). We identified 16 SNPs associated with glioma risk at the 1% significance level. The highest association observed across the five independent case-control datasets involved rs243356, which maps to intron 3 of CHAF1A (trend odds ratio, 1.32; 95% confidence interval 1.14-1.54; P = 0.0002; false-positive report probability = 0.055, based on a prior probability of 0.01). Our results provide additional support for the hypothesis that low penetrance variants contribute to the risk of developing glioma and suggest that a genetic variant located in or around the CHAF1A gene contributes to disease risk.

An inverse association between allergic conditions and glioma risk has been reported previously. In this large population-based case-control study, the authors identified cases diagnosed with glioma or meningioma in Denmark, Norway, Finland, Sweden, and southeast England between 2000 and 2004. Detailed information on self-reported physician-diagnosed allergic conditions was collected from 1,527 glioma cases, 1,210 meningioma cases, and 3,309 randomly selected controls. Logistic regression showed an odds ratio of 0.70 (95% confidence interval: 0.61, 0.80) for glioma associated with a diagnosis of any of asthma, hay fever, eczema, or other type of allergy. The risk estimates for glioma were around 0.65 for each allergic condition (asthma, eczema, hay fever, and food allergy), and the 95% confidence intervals were equally consistent, at around 0.55, 0.80. The reduced risks of glioma related to eczema, hay fever, and allergy overall, but not asthma, were confined to current rather than past conditions. Meningioma risk was not associated with allergic conditions, except for eczema (odds ratio = 0.74, 95% confidence interval: 0.60, 0.91). Our results show a reduced risk for glioma associated primarily with current allergic conditions. If this is etiologic, it has implications for the understanding of how allergic conditions might reduce the tumor risk.

Background: P53 and ATM are central checkpoint genes involved in the repair of DNA damage after ionising irradiation, which has been associated with risk of brain tumours. Therefore, we tested the hypothesis that polymorphisms and haplotypes in p53 and ATM could be associated with glioma and meningioma risk., Material and Methods: Six hundred and eighty glioma cases (298 glioblastoma (GBM)), 503 meningioma cases, and 1555 controls recruited in the Nordic-UK Interphone study, were analysed in association with three polymorphisms in p53 (rs2287499, rs1042533, rs1625895) and five polymorphisms in ATM ( rs228599, rs3092992, rs664143, rs170548, rs3092993). Haplotypes were constructed using the HAPLOSTAT program., Results: The global statistical test of glioblastoma and p53 haplotypes was p = 0.02. The haplotype analysis on glioblastoma revealed the 1-2-2 haplotype (promotor-codon72-intron 6) had a frequency of 6.1% in cases compared with 9.8% in controls (p = 0.003). The 1-2-1 haplotype was significantly more frequent in GBM cases, 10.2%, than in controls, 7.3% (p = 0.02). The haplotype analysis in ATM revealed an increased frequency of the 1-1-1-2-1 haplotype in meningioma cases (33.8%) compared with controls (30.3%) (p = 0.03). The 2-1-2-1-1 haplotype had a lower frequency in meningioma cases (36.1%) than controls (40.7%) (p = 0.009)., Conclusions: This study found both positive and negative associations of haplotypes in p53 for glioblastoma and ATM for meningioma. This study provides new data that could add to our understanding of brain tumour susceptibility.

Public concern has been expressed about the possible adverse health effects of mobile telephones, mainly related to intracranial tumors. We conducted a population-based case-control study to investigate the relationship between mobile phone use and risk of glioma among 1,522 glioma patients and 3,301 controls. We found no evidence of increased risk of glioma related to regular mobile phone use (odds ratio, OR = 0.78, 95% confidence interval, CI: 0.68, 0.91). No significant association was found across categories with duration of use, years since first use, cumulative number of calls or cumulative hours of use. When the linear trend was examined, the OR for cumulative hours of mobile phone use was 1.006 (1.002, 1.010) per 100 hr, but no such relationship was found for the years of use or the number of calls. We found no increased risks when analogue and digital phones were analyzed separately. For more than 10 years of mobile phone use reported on the side of the head where the tumor was located, an increased OR of borderline statistical significance (OR = 1.39, 95% CI 1.01, 1.92, p trend 0.04) was found, whereas similar use on the opposite side of the head resulted in an OR of 0.98 (95% CI 0.71, 1.37). Although our results overall do not indicate an increased risk of glioma in relation to mobile phone use, the possible risk in the most heavily exposed part of the brain with long-term use needs to be explored further before firm conclusions can be drawn., ((c) 2007 Wiley-Liss, Inc.)

Background: Glutathione transferases (GST) detoxify environmental and endogenous compounds and levels of two polymorphic GST proteins, GSTM3 and GSTP1, are high in the brain. Previous studies of GSTM3 and GSTP1 polymorphisms and adult brain tumor risk have produced inconsistent results, whereas the GSTM3 -63 variant is newly identified and, therefore, has not yet been studied in this context. We therefore examined associations between GSTM3 -63, GSTM3 *A/*B, GSTP1 105, and GSTP1 114 variants and adult brain tumor risk and the interaction of the effects of these same polymorphisms with cigarette smoking. In addition, the enzymes NQO1 and CYP1A1 alter susceptibility to oxidative brain damage. Because there is less previous evidence for a role of NQO1, CYP1A1, GSTM1, and GSTT1 variants, we restricted analysis of these variants to a small preliminary study., Methods: We genotyped DNA collected for an international population-based case-control study of 725 glioma cases, 329 of which were glioblastoma cases, 546 meningioma cases and 1,612 controls. Study participants were residents of Sweden, southeast England, Denmark, and Finland., Results: We found no associations between the GSTM3, GSTP1, NQO1, CYP1A1, GSTM1, or GSTT1 polymorphisms and adult brain tumor risk with the possible exception of a weak association between the G-C (Val-Ala) GSTP1 105/114 haplotype and glioma [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54, 0.99], nor was there an interaction between the effects of the GSTM3 or GSTP1 polymorphisms and cigarette smoking., Conclusions: Overall, we observed no strong evidence for an association between GST or related enzyme polymorphisms and adult brain tumor risk.

Brain tumors are some of the most lethal adult cancers and there is a concern that the incidence is increasing. It has been suggested that the reported increased incidence can be explained by improvements in diagnostic procedures, although this has not been totally resolved. The aim of our study was to describe the incidence trends of adult primary intracerebral tumors in four Nordic countries during a period with introduction of new diagnostic procedures and increasing prevalence of mobile phone users. Information about benign and malignant primary intracerebral tumor cases 20-79 years of age was obtained from the national cancer registries in Denmark, Finland, Norway and Sweden for the years 1969-98 and estimates of person-years at risk were calculated from the information obtained from national population registries. Annual age standardized incidence rates per 100,000 person-years were calculated and time trends analyses were carried out using Poisson regression. The overall incidence of all intracerebral tumors ranged from 8.4-11.8 for men and 5.8-9.3 for women, corresponding to an average annual increase of 0.6% for men (95% confidence interval [CI] = 0.4, 0.7) and 0.9% for women (95% CI = 0.7, 1.0). The increase in the incidence was confined to the late 1970s and early 1980s and coinciding with introduction of improved diagnostic methods. This increase was largely confined to the oldest age group. After 1983 and during the period with increasing prevalence of mobile phone users, the incidence has remained relatively stable for both men and women., (Copyright 2003 Wiley-Liss, Inc.)

Objective: The objective of this study was to determine the nationwide, population-based incidences of intracranial gliomas and meningiomas (of all grades) during 55 years of monitoring in Denmark., Methods: On the basis of reports in the Danish Cancer Registry, we calculated age-standardized, period-specific incidences and age- and birth cohort-specific incidences, in 5-year age and calendar intervals, for intracranial gliomas and meningiomas., Results: The incidence of gliomas increased 1.7-fold from 1943 to 1947 to 1993 to 1997, whereas the incidence for meningiomas increased 3.9-fold during the same period., Conclusion: Based on complete notification to the Danish Cancer Registry, the overall incidences of intracranial gliomas and meningiomas increased during a 55-year period. These increases were observed for all age groups and both sexes. These increases could be explained on the basis of improved diagnoses of these tumors. For gliomas, a maximal annual incidence of approximately 4 cases/100,000 population (World Standard Population) was observed in Denmark at the end of the study period, suggesting that the effects of improved diagnostic tools have reached their maximum with respect to this tumor type. The same was not observed for the incidence of meningiomas, suggesting that perhaps underreporting is still present.