Cohort studies of association between self-reported allergic conditions,immune-related diagnoses and glioma and meningioma risk

An inverse association between self-reported allergies and glioma and meningioma risk, has been previously observed in case-control studies. Approximately 27% (median) of the information on both glioma and meningioma in these studies, however, is collected from proxy respondents. In fact, the odds ratios (OR) among previous brain tumor studies are inversely related to the proportion of proxy respondents (Pearson correlation coefficient = -0.94; 95% CI = -1.00 to -0.65); this correlation suggests bias. We therefore constructed 3 cohorts based on the Swedish Twin, Hospital Discharge, and Cancer Registries. In Cohorts I (14,535 people developed 37 gliomas and 41 meningiomas) and II (29,573 people developed 42 gliomas and 26 meningiomas) median time from self-report of allergies to brain tumor diagnosis was 15.4 years. Cohort III, which overlaps with Cohorts I and II (52,067 people developed 68 gliomas and 63 meningiomas), was linked to the Swedish Hospital Discharge Registry where pre-brain tumor immune-related discharge diagnoses were recorded. Allergies are inversely associated with glioma risk in Cohort I (Hazard ratio [HR] = 0.45; 95% CI = 0.19-1.07) and among high grade (III and IV, HR = 0.45; 95% CI = 0.11-1.92) but not low grade (I and II, HR = 2.60; 95% CI = 0.86-7.81) gliomas in Cohort II. In Cohort III, immune-related discharge diagnoses are also inversely associated with glioma (HR = 0.46; 95% CI = 0.14-1.49). There is no strong evidence against (and some for) the hypothesis that allergies reduce glioma risk.     

Reproductive factors and risk of meningioma and glioma

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.     

Risk factors for gliomas and meningiomas in males in Los Angeles County

Detailed job histories and information about other suspected risk factors were obtained during interviews with 272 men aged 25-69 with a primary brain tumor first diagnosed during 1980-1984 and with 272 individually matched neighbor controls. Separate analyses were conducted for the 202 glioma pairs and the 70 meningioma pairs. Meningioma, but not glioma, was related to having a serious head injury 20 or more years before diagnosis [odds ratio (OR) = 2.3; 95% confidence interval (CI) = 1.1-5.4], and a clear dose-response effect was observed relating meningioma risk to number of serious head injuries (P for trend = 0.01; OR for greater than or equal to 3 injuries = 6.2; CI = 1.2-31.7). Frequency of full-mouth dental X-ray examinations after age 25 related to both glioma (P for trend = 0.04) and meningioma risk (P for trend = 0.06). Glioma, but not meningioma risk, related to duration of prior employment in jobs likely to involve high exposure to electric and magnetic fields (P for trend = 0.05). This risk was greatest for astrocytoma (OR for employment in such jobs for greater than 5 years = 4.3; CI = 1.2-15.6). More glioma cases had worked in the rubber industry (discordant pairs 6/1) and more worked in hot processes using plastics (9/1). More meningioma cases had jobs that involved exposure to metal dusts and fumes (discordant pairs 13/5), and six of these cases and two controls worked as machinists. Finally, there was a protective effect among glioma pairs relating to frequency of use of vitamin C and other vitamin supplements (P for trend = 0.004); the OR for use at least twice a day was 0.4 (CI = 0.2-0.8).     

p53 Genotypes and risk of glioma and meningioma.

Brain tumors have previously been associated with the Li-Fraumeni syndrome that often is caused by p53 germ line mutations. Therefore, we investigated if polymorphisms of p53 were associated with an increased risk of meningioma and glioma and integrated the polymorphism analyses with detailed information on family history of cancer. In a population-based case-control study, DNA was extracted from 205 glioma and 164 meningioma cases identified during 2000 to 2002 in Sweden and from 374 controls selected randomly from the general population, stratified on age, sex, and geographic region. The Swedish Cancer Registry confirmed a cancer in family members in 86% of cases and controls that reported a family history of cancer. p53 single nucleotide polymorphism (SNP) analyses were done on three SNPs from the promoter region, codon 72 in exon 4, and intron 6. Overall, no associations were found for any of the SNPs. Analyses of the combinations of the three SNPs were also done. The CC-CG-CC-specific polymorphism combination was associated with an odds ratio (OR) of 1.36 [95% confidence interval (95% CI), 0.68-2.72] for glioma and 1.36 (0.64-2.88) for meningioma. When restricting the analyses to cases and controls with a positive family history of cancer, the corresponding results were OR of 3.62 (95% CI, 1.05-12.48) for glioma and 5.69 (1.81-17.96) for meningioma. This study is novel in suggesting an increased risk of brain tumors when the analysis is restricted to those with a history of cancer in the family. However, we cannot rule out the possibility that these results are due to chance.     

Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial.

Studies on the relationship between obesity and prostate cancer incidence are inconsistent. In part, this inconsistency may be due to a differential effect of obesity on low-grade and high-grade cancer or confounding of the association of obesity with prostate cancer risk by diabetes. We investigated the associations of obesity and diabetes with low-grade and high-grade prostate cancer risk. Data were from 10,258 participants (1,936 prostate cancers) in the Prostate Cancer Prevention Trial who all had cancer presence or absence determined by prostate biopsy. Multiple logistic regression was used to model the risk of total prostate cancer, and polytomous logistic regression was used to model the risk of low-grade and high-grade prostate cancer. Compared with men with body mass index < 25, obese men (body mass index > or =30) had an 18% [odds ratio (OR), 0.82; 95% confidence interval (95% CI), 0.69-0.98] decreased risk of low-grade prostate cancer (Gleason <7) and a 29% (OR, 1.29; 95% CI, 1.01-1.67) increased risk of high-grade prostate cancer (Gleason > or =7) or, alternatively, a 78% (OR, 1.78; 95% CI, 1.10-2.87) increased risk defining high-grade cancer as Gleason sum 8 to 10. Diabetes was associated with a 47% (OR, 0.53; 95% CI, 0.34-0.83) reduced risk of low-grade prostate cancer and a 28% (OR, 0.72; 95% CI, 0.55-0.94) reduced risk of high-grade prostate cancer. Associations of obesity or diabetes with cancer risk were not substantially changed by mutually statistical controlling for each other. Obesity increases the risk of high-grade but decreases the risk of low-grade prostate cancer, and this relationship is independent of the lower risk for prostate cancer among men with diabetes.     

Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas: data from the SEER program, 1973-2001

BACKGROUND: Detailed population-based estimates of long-term survival as well as patterns of care for patients with low-grade gliomas examined by age at diagnosis, gender, and race have not been widely available. METHODS: Time to death was examined among 2009 individuals diagnosed with a supratentorial low-grade glioma and reported to the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute from 1973-2001 using Kaplan-Meier estimation. A Cox proportional hazards model was used to assess the effect of age at diagnosis, race, gender, histology, anatomic location within the brain, first course of treatment, and year of diagnosis upon this risk. RESULTS: The cumulative 5-, 10-, 15- and 20-year survival rates among all individuals initially diagnosed with a supratentorial low-grade glioma were 59.9% (95% confidence interval [95% CI], 57.6-62.2); 42.6% (95% CI, 39.9-45.2); 31.9% (95% CI, 29.0-34.8); and 26.0% (95% CI, 22.7-29.2), respectively. Improved survival was significantly associated with female gender (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), younger age, white race (HR, 0.70; 95% CI, 0.54-0.93), histology, and later year of diagnosis. Surgical treatment was associated with increased survival. The use of radiation therapy as a first course of treatment for these lesions has significantly decreased over time with the majority of patients receiving only surgery as a first course of treatment. CONCLUSIONS: Data for patients diagnosed with low-grade gliomas revealed increasing survival times over the past 25 years with a subset of patients surviving for decades. Differences in survival by race, gender, histology, and first course of treatment were appreciated. These data suggested that the clinical course of low-grade glioma for some patients may be more encouraging than previously perceived and that the identification of this group of patients may allow refinement of current treatment protocols.     

Genetic polymorphisms of glutathione S-transferases and the risk of adult brain tumors: a meta-analysis.

BACKGROUND: Studies investigating the association between genetic polymorphisms of glutathione S-transferases (GST) and risk of adult brain tumors have reported conflicting results. The rationale of this meta-analysis was to determine whether GST variants increase the susceptibility of adult brain tumors by pooling data. METHODS: Two investigators independently searched the HuGENet database, MEDLINE, EMBASE, conference articles, and manually reviewed bibliographies of retrieved articles. Papers were included if they were observational studies investigating the influence of GSTM1, GSTT1, GSTP1 I105V, or GSTP1 A114V on the development of adult brain cancers. Potential sources of heterogeneity between studies were explored in a meta-regression. RESULTS: We identified eight eligible studies, which included 1,630 cases of glioma, 245 cases of meningioma, and 7,151 controls. Using the random effects model, there was no association between any of the GST variants and the risk of glioma [overall odds ratio (OR), 1.08; 95% confidence interval (95% CI), 0.95-1.22]. Subgroup analyses also showed no relationship between GST variants and histopathologic groups; the overall ORs were 1.13 (95% CI, 0.88-1.43) for high-grade glioma and 1.08 (95% CI, 0.76-1.55) for low-grade glioma. A random effects meta-regression suggested that the use of in-hospital controls produced larger effect estimates in glioma than the use of population controls (overall OR, 1.30; 95% CI, 1.03-1.65). The T1 null genotype was significantly associated with a risk of meningioma (OR, 1.95; 95% CI, 1.02-3.76), but the M1 variant was not. CONCLUSION: This study did not suggest any relationship between GST variants and risks of glioma; the T1 null genotype may influence the susceptibility of meningioma, but larger studies are needed to substantiate this relationship.     

Role of medical history in brain tumour development. Results from the international adult brain tumour study.

In an international population-based case-control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age- and gender-matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR = 6.55, 95% CI 3.40-12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti-epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR = 0.59, 95% CI 0.49-0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR = 0.72, 95% CI 0.61-0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation.     

History of allergies and autoimmune diseases and risk of brain tumors in adults

To explore a possible influence of the immune system in the development of brain tumors, we evaluated the relationship between history of allergies and autoimmune diseases and risk of brain tumors within a large, hospital-based case-control study. Cases (n = 782) were patients recently diagnosed with glioma (n = 489), meningioma (n = 197) or acoustic neuroma (n = 96) at hospitals in Boston, Phoenix and Pittsburgh (USA). Controls (n =799) were patients hospitalized for a variety of nonmalignant conditions and frequency-matched to cases by hospital, age, sex, race/ethnicity and distance of residence from hospital. Research nurses collected data by personal interview of patients. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. There was a significant inverse association between glioma and history of any allergies (OR = 0.67, 95% CI = 0.52-0.86) or autoimmune diseases (OR = 0.49, 95% CI = 0.35-0.69). No significant associations were evident for meningioma or acoustic neuroma with history of any allergies. An inverse association was observed between meningioma and history of autoimmune diseases (OR = 0.59, 95% CI = 0.38-0.92). There was a suggestion of interaction between allergies and autoimmune diseases on risk of glioma (p = 0.06), with subjects having both conditions being at lowest risk (OR = 0.24, 95% CI = 0.14-0.42). Among the specific conditions, asthma and diabetes showed the most consistent associations (OR = 0.63, 95% CI = 0.43-0.92 and OR = 0.44, 95% CI = 0.27-0.70, respectively). Our results add to evidence that persons with allergies or autoimmune diseases are at reduced risk of glioma. The basis of the associations is not clear, but they might imply a role of immunologic factors in the development of brain tumors. Published 2002 Wiley-Liss, Inc.     

Maternal and perinatal risk factors for childhood leukemia

This report describes an exploratory population-based study of maternal and perinatal risk factors for childhood leukemia in Sweden. The Swedish National Cancer Registry ascertained 411 cases in successive birth cohorts from 1973 through 1984 recorded in the Swedish Medical Birth Registry. Using the latter, we matched five controls without cancer to each case by sex and month and year of birth. Mothers of children with leukemia were more likely to have been exposed to nitrous oxide anesthesia during delivery than mothers of controls [odds ratio (OR) = 1.3; 95% confidence interval (CI) = 1.0, 1.6]. Children with leukemia were more likely than controls to have Down's syndrome (OR = 32.5; 95% CI = 7.3, 144.0) or cleft lip or cleft palate (OR = 5.0; 95% CI = 1.0, 24.8); to have had a diagnosis associated with difficult labor but unspecified complications (OR = 4.5; 95% CI = 1.1, 18.2) or with other conditions of the fetus or newborn (OR = 1.5; 95% CI = 1.1, 2.1), specifically, uncomplicated physiological jaundice (OR = 1.9; 95% CI = 1.2, 2.9); or to have received supplemental oxygen (OR = 2.6; 95% CI = 1.3, 1.3, 4.9). Because multiple potential risk factors were analyzed in this study, future studies need to check these findings. We did not confirm the previously reported higher risks for childhood leukemia associated with being male, having a high birth weight, or being born to a woman of advanced maternal age.     

Polymorphisms in apoptosis and cell cycle control genes and risk of brain tumors in adults.

Despite the potential importance of the cell cycle and apoptosis pathways in brain tumor etiology, little has been published regarding brain tumor risk associated with common gene variants in these pathways. Using data from a hospital-based case-control study conducted by the National Cancer Institute between 1994 and 1998, we evaluated risk of glioma (n = 388), meningioma (n = 162), and acoustic neuroma (n = 73) with respect to 12 single nucleotide polymorphisms from 10 genes involved in apoptosis and cell cycle control: CASP8, CCND1, CCNH, CDKN1A, CDKN2A, CHEK1, CHEK2, MDM2, PTEN, and TP53. We observed significantly decreased risk of meningioma with the CASP8 Ex14-271A>T variant [odds ratio (OR)(AT), 0.8; 95% confidence interval (95% CI), 0.5-1.2; OR(AA), 0.5; 95% CI, 0.3-0.9; P(trend) = 0.03] and increased risk of meningioma with the CASP8 Ex13+51G>C variant (OR(GC), 1.4; 95% CI, 0.9-2.1; OR(CC), 3.6; 95% CI, 1.0-13.1; P(trend) = 0.04). The CT haplotype of the two CASP8 polymorphisms was associated with significantly increased risk of meningioma (OR, 1.7; 95% CI, 1.1-2.6), but was not associated with risk of glioma or acoustic neuroma. The CCND1 Ex4-1G>A variant was associated with increased risk for glioma, and the Ex8+49T>C variant of CCNH was associated with increased risk of glioma and acoustic neuroma. The MDM2 Ex12+162A>G variant was associated with significantly reduced risk of glioma. Our results suggest that common variants in the CASP8, CCND1, CCNH, and MDM2 genes may influence brain tumor risk. Future research in this area should include more detailed coverage of genes in the apoptosis/cell cycle control pathways.     

Occupational risk factors for low grade and high grade glioma: results from an international case control study of adult brain tumours

The majority of suspected occupational risk factors for adult brain tumours have yet to be confirmed as etiologically relevant. Within an international case-control study on brain tumours, lifelong occupational histories and information on exposures to specific substances were obtained by direct interviews to further investigate occupational risk factors for glioma. This is one of the largest studies of brain tumours in adults, including 1,178 cases and 1987 population controls from 8 collaborating study centres matched for age, gender and centre. All occupational information, was aggregated into 16 occupational categories. In a pooled analysis, odds ratios (OR), adjusted for education, were estimated separately for men and women and for high-grade glioma (HGG) and low-grade glioma (LGG), focusing especially on 6 categories defined a priori: agricultural, chemical, construction, metal, electrical/electronic and transport. For men, an elevated OR of glioma associated with the category "metal" (OR = 1.24, 95% CI 0.96-1.62) was seen, which appeared to be largely accounted for by LGG (OR = 1.59, 95% CI 1.00-2.52). For the other 5 occupational categories, no elevated risks for glioma were observed. For women the only noteworthy observation for the 6 a priori categories was an inverse association with the "agriculture" category (OR = 0.60, 95% CI 0.36-0.99). Apart from the 6 major categories, women working in food production or food processing (category "food") showed an increased OR of 1.95 (95% CI 1.04-3.68). None of the 20 substance groups was positively associated with glioma risk. Although some other point estimates were elevated, they lacked statistical significance. The results do not provide evidence of a strong association between occupational exposures and glioma development.     

Possible interaction between ionizing radiation, smoking, and gender in the causation of meningioma

Data on the association between smoking and meningioma are inconsistent. The aim of this study was to assess the role of smoking in radiation- and non-radiation-related meningiomas. The study was designed as a 4-group case-control study, balanced for irradiation, including 160 irradiated meningioma case patients, 145 irradiated control subjects, 82 nonirradiated case patients, and 135 nonirradiated control subjects. The sources of these groups included a cohort of individuals who underwent radiotherapy (mean dose, 1.5 Gy to the brain) during childhood for treatment of tinea capitis, claims filed for radiation damage in the framework of a compensation law, and the Israel Cancer Registry. All tests of statistical significance were 2-sided. A statistically significantly elevated risk of meningioma was found among men who had ever smoked, compared with those who were never smokers (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.09-4.15), increasing with smoking pack-years from 1.67 to 2.69 for <10 to >20 pack-years, respectively. Among women, an interaction between radiation and smoking was observed, expressed by a significant protective effect for meningioma (OR, 0.32; 95% CI, 0.14-0.77), with a strong dose-response association (P < .01) in non-irradiated women and a nonsignificant increased risk of meningioma among those who were irradiated (OR, 1.23; 95% CI, 0.68-2.23). Variation in the association between smoking and meningioma may be explained by effects of distinct host factors, such as past exposure to ionizing radiation and/or hormonal factors.     

Maternal and perinatal risk factors for Wilms' tumor: a nationwide nested case-control study in Sweden.

This report describes maternal and perinatal risk factors for Wilms' tumor analyzed in a case-control study nested in a nationwide cohort in Sweden. The Swedish National Cancer Registry ascertained 110 cases from among successive birth cohorts from 1973 through 1984, identified by the Swedish Medical Birth Registry, the latter based on medical records. From the Birth Registry, we matched 5 controls without cancer to each case by sex and date of birth. Wilms'-tumor children were more likely to have mothers who had been exposed to penthrane (methoxyflurane) anesthesia during delivery than mothers of controls (odds ratio (OR) = 2.4; 95% confidence interval (CI) 1.1 to 5.1); this excess risk was higher in females than males and increased with age at diagnosis. Wilms'-tumor cases were also more likely to have had physiologic jaundice (OR = 2.3; 95% CI 1.1 to 5.0). Higher parity of the mother decreased the risk of Wilms' tumor among females (OR = 0.7; 95% CI 0.5 to 1.0). We were unable to confirm the reported increased risks of Wilms' tumor for those with high birth weights or with a maternal history of hypertension or fluid retention during pregnancy, nor did we find any association with mother's age at delivery, previous stillbirth, previous live birth, gestational length or height of the child.     

Genetic variation in insulin-like growth factors and brain tumor risk

Many studies support a role for insulin-like growth factors (IGFs) in the regulation of tumor cell biology. We hypothesized that single-nucleotide polymorphisms (SNPs) in IGF genes are risk factors for glioma and meningioma. To test the hypothesis, we examined associations of brain tumor risk with nine variants in five IGF genes in a hospital-based case-control study. The study was conducted at hospitals in Boston, Phoenix, and Pittsburgh between 1994 and 1998. Eligible cases were individuals (18 years or older) newly diagnosed with glioma or meningioma. Controls were selected among patients who were admitted to the same hospitals for a variety of nonmalignant conditions and frequency matched to cases by hospital, age, sex, race, and distance from residence. The present analysis was restricted to non-Hispanic whites. DNA was extracted from blood samples collected from 354 glioma cases, 133 meningioma cases, and 495 control individuals. We evaluated nine SNPs in five IGF genes (IGF1, IGF1R, IGF2, IGF2R, and IGFBP3). The majority of the analyzed IGF SNPs did not display statistically significant associations with glioma or meningioma. For glioma, one IGF1R SNP (rs2272037) indicated a possible association. No indications of association were seen for glioblastoma, but for low-grade gliomas, the odds ratio under a dominant model was 0.56 (95% confidence interval [CI], 0.35-0.90) for IGF1 rs6220, 2.98 (95% CI, 1.65-5.38) for IGF1R rs2272037, and 1.60 (95% CI, 0.90-2.83) for IGF1R rs2016347. Overall, our results do not provide strong evidence of associations of brain tumor risk with IGF polymorphic variants but identify several associations for glioma that warrant further examination in other, larger studies.     

Handedness and risk of brain tumors in adults.

The objective of this study was to evaluate the relation between handedness, and the risk of malignant and benign brain tumors. Handedness has been hypothesized to serve as a behavioral marker of prenatal hormonal exposures or other factors that influence subsequent cancer risk. A case-control study was conducted at hospitals in three United States cities between 1994 and 1998. The cases were adult patients newly diagnosed with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96), and the 799 frequency-matched controls were patients admitted to the same hospitals for a variety of nonmalignant conditions. Handedness was determined by interview. Unconditional logistic regression was used to estimate odds ratios (ORs) and calculate 95% confidence intervals (CIs). Persons who described themselves as left-handed or ambidextrous appeared to be at reduced risk of glioma relative to those who described themselves as right-handed (OR, 0.7; 95% CI, 0.5-0.9). The association was similar for men and women, and for left-sided and right-sided tumors. Neither meningioma (OR, 0.9; CI, 0.6-1.5) nor acoustic neuroma (OR, 0.9; CI, 0.5-1.7) showed significant associations with handedness. These findings require confirmation but raise the possibility that early neurodevelopmental events or genetic factors related to handedness also influence the risk of glioma among adults.     

Reproductive factors and risk of primary brain tumors in women

Gender-specific incidence patterns and the presence of hormonal receptors on tumor cells suggest that sex hormones may play a role in the onset of primary brain tumors. However, epidemiological studies on the relation of hormonal risk factors to the risk of brain tumors have been inconsistent. We examined the role of reproductive factors in the onset of glioma and meningioma in a case–control study conducted in the Southeastern US that included 507 glioma cases, 247 meningioma cases, and 695 community-based and friend controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CI) adjusting for age, race, US state of residence, and education. An older age at menarche was associated with an increased risk of glioma (≥15 vs. ≤12 years: OR 1.65; 95 % CI 1.11–2.45), with a stronger association observed in pre-menopausal (OR 2.22; 95 % CI 1.12–4.39) than post-menopausal (OR 1.55; 95 % CI 0.93–2.58) women. When compared to controls, meningioma cases were more likely to have undergone natural menopause (OR 1.52; 95 % CI 1.04–2.21) whereas glioma cases were less likely to be long term users of oral contraceptives (OR 0.47; 95 % CI 0.33–0.68). Increasing parity was not related to the risk of either tumor. Current findings are consistent with a limited role for hormones in the onset of brain tumors in women. Results contribute to a growing body of evidence that a later age at menarche increases the risk of glioma in women.     

Meningioma and schwannoma risk in adults in relation to family history of cancer

Relatively little is known about factors that contribute to the development of meningioma and vestibular schwannoma, two intracranial nervous system tumors. We evaluated the risk of these tumors in relation to family history of malignant or benign tumors. Incident cases of meningioma (n = 197) or schwannoma (n = 96) were identified at three U. S. referral hospitals between June 1994 and August 1998. Controls (n = 799) admitted to the same hospitals for nonmalignant conditions were matched to cases on age, sex, race/ethnicity, hospital, and proximity of residence to hospital. We found that risk of meningioma was increased among persons reporting a family history of a benign brain tumor (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.0-21.0; n = 5) or melanoma (OR, 4.2; 95% CI, 1.2-15.0; n 5). A family history of breast cancer was associated with an elevated meningioma risk among participants aged 18 to 49 years (OR, 3.9; 95% CI, 1.4-11.0; n = 8) but a reduced risk among older respondents (OR, 0.2; 95% CI, 0.1-0.7; n = 3). Family history of cancer did not differ between schwannoma cases and controls, although the statistical power to detect associations was limited. Some relative risk estimates were based on a small number of observations and may have arisen by chance. Inheritance of predisposing genes, shared environmental factors, or both within families with a history of benign brain tumors, melanoma, or possibly breast cancer may be related to altered meningioma risk.     

Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma.

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.