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Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and hence a defence against cancer. The CASP8 polymorphism D302H has recently been shown to influence the risk of breast cancer. We tested the hypothesis that the CASP8 polymorphism D302H may influence risk of meningioma through analysis of five independent series of case patients and controls (n=631 and 637, respectively). Carrier status for 302H was not associated with a statistically significantly increased risk (OR=1.16; 95% CI: 0.87-1.53; P=0.31) making it unlikely that this variant contributes to the inherited risk of meningioma.

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.

Background: Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility., Methods: We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case-control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided., Results: The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1-interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; P(trend) = 8.95 x 10(-6); P = .009 after adjusting for multiple testing)., Conclusions: We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma.

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.

The female predominance in meningioma incidence and association between meningioma and breast cancer suggest that growth of meningiomas is hormone-dependent. There are several discrepancies in literature about the proliferative effect of sex hormones on meningiomas. This study aims to evaluate the hormone receptor status of meningiomas and assess its relation to age, sex, histological grade, recurrence, and proliferation activity. The material was based on consecutive patients operated for meningioma at Tampere University Hospital in 1989-1999. The occurrence of progesterone, estrogen and androgen receptor in patients with primary and recurrent meningiomas was studied immunohistochemically by using specific monoclonal antibodies. Hormonal status was determined in 510 tumor samples. 443 samples were from primary meningiomas and 67 from recurrent tumors. Of the samples, 455 were benign (WHO grade I), 49 atypical (grade II), and 6 malignant (grade III). Of the primary tumor samples, 88% were progesterone receptor positive, 40% were positive for estrogen and 39% for androgen receptors. Grade I meningiomas had significantly higher incidence for estrogen and androgen receptors than higher grade meningiomas. Estrogen positive tumor samples had significantly higher proliferation index than estrogen negative samples. No difference in expression of sex hormone receptors was observed by sexes or age group. Estrogen and androgen receptors may have more influence on the pathogenesis of meningiomas than earlier thought. The higher incidence of meningiomas in women can not be explained by differences of sex hormone receptor expression.

It has been reported that the incidence of meningioma increased in several industrialized countries in the late 1970s and early 1980s. The aim of this study was to evaluate the time trends in incidence of meningiomas in Denmark, Finland, Norway and Sweden, with emphasis on the age distribution and sex ratio. Information about cases of meningiomas in people aged 15-84 years was obtained from the cancer registries of these Nordic countries for the years 1968-1997, and estimates of person-years at risk were calculated from information provided by the national population registries. Age-specific incidence rates per 100,000 and incidence rate ratios were calculated for 3-year periods. The female:male ratios were also evaluated. The combined incidence among men increased from 1.4 to 1.9 per 100,000 during the follow-up period, the corresponding rates for women were 2.6 and 4.5. The female:male ratio increased over time for several age groups and was as high as 3.5:1 in the group aged 40-44 years in the latest follow-up period (1993-1997). In summary, our results provide some support for the idea that the introduction of computed tomography in the late 1970s has had an impact on the detection of cases in people aged 60 and over. The decrease in the rate or detection postmortem has affected the incidence time trend, but it also coincides with widespread use of new imaging technologies. The increasing trend shown for the female:male ratio in the group aged 35-59 years is consistent with the possibility that increasing use of hormones may affect the incidence of meningiomas in women., (Copyright 2005 Wiley-Liss, Inc)

Background Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility. Methods We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case-control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided. Results The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1-interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; Ptrend = 8.95 × 10-6; P= .009 after adjusting for multiple testing). Conclusions We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the possible selection bias related to the differential participation of mobile phone users and non-users in a Finnish case–control study on mobile phone use and brain tumors. Methods: Mobile phone use was investigated among 777 controls and 726 cases participating in the full personal interview (full participants), and 321 controls and 103 cases giving only a brief phone interview (incomplete participants). To assess selection bias, the Mantel-Haenszel estimate of odds ratio was calculated for three different groups: full study participants, incomplete participants, and a combined group consisting of both full and incomplete participants. Results: Among controls, 83% of the full participants and 73% of the incomplete participants had regularly used a mobile phone. Among cases, the figures were 76% and 64%, respectively. The odds ratio for brain tumor based on the combined group of full and incomplete participants was slightly closer to unity than that based only on the full participants. Conclusions: Selection bias tends to distort the effect estimates below unity, while analyses based on more comprehensive material gave results close to unity. [Copyright &y& Elsevier]