Lower Glioma Risk Research Articles

Chinese Dietary Indices and Glioma: New Insights of a Case-Control Study in the Chinese Population.

Identifying modifiable factors in primary prevention strategies is a typical goal of glioma epidemiology. Among many glioma risk factors, diet was always considered as one. Most of the relevant studies thus far were concentrated on the West. It was crucial to investigate the connection between the Chinese diet and gliomas given the stark variations between western and eastern diets. A food frequency questionnaire including 114 items was used to investigate the food intake of the study subjects. The Chinese Dietary Quality Index (CDQI), the Chinese Dietary Balance Index (CDBI), the Dietary Antioxidant Index (DAI), the Dietary Inflammation Index (DII), and the Chinese Healthy Eating Index (CHEI) were calculated based on the data provided by the food frequency questionnaire to evaluate dietary quality, dietary balance, dietary antioxidants, dietary inflammation and adherence to the Chinese dietary guidelines in 506 glioma patients and 506 controls, respectively. After adjusting covariates, CHEI (OR = 0.90, 95% CI: 0.88-0.93) and DAI (OR = 0.61, 95% CI: 0.54-0.70) were correlated to a reduced glioma risk, and CDBI-based undernutrition (OR = 1.08, 95% CI: 1.06-1.12) and overnutrition (OR = 1.14, 95% CI: 1.09-1.20) and DII (OR = 2.20, 95% CI: 1.81-2.68) were correlated to an elevated glioma risk. Moreover, restrictive cubic spline analysis showed that there were significant nonlinear dose-response relationships between CHEI, CDBI, DAI, DII, and glioma. Therefore, adhering to the Chinese dietary guidelines was connected with a lower glioma risk, and undernutrition and overnutrition in the Chinese diet were associated with an increased risk of glioma.

Prospective investigation of herpesvirus infection and risk of glioma.

Glioma is an aggressive neoplasm of the brain with poorly understood etiology. A limited number of pathogens have been examined as glioma risk factors, but data from prospective studies with infection status determined before disease are lacking. Herpesviruses comprise a large family of DNA viruses that infect humans and are linked to a range of chronic diseases. We conducted a prospective evaluation of the association between antibody to six human herpesviruses and glioma risk in the Janus Serum Bank (Janus) and the Cancer Prevention Study-II (CPS-II). In Janus and CPS-II, the risk for glioma was not related to seroprevalence of herpes simplex virus-1, varicella zoster virus, or human herpes viruses 6A or 6B. In Janus, seropositivity to either the Epstein Barr virus (EBV) EA[D] or VCAp18 antigen was associated with a lower risk of glioma (ORs: 0.55 [95% CI 0.32-0.94] and 0.57 [95% CI 0.38-0.85]). This inverse association was consistent by histologic subtype and was observed for gliomas diagnosed up to two decades following antibody measurement. In Janus, seropositivity to at least one of three examined cytomegalovirus (CMV) antigens (pp150, pp52, pp28) was associated with an increased risk of nonglioblastoma (OR: 2.08 [95% CI 1.07-4.03]). This association was limited to tumors diagnosed within 12 years of antibody measurement. In summary, we report evidence of an inverse association between exposure to EBV and glioma. We further report that CMV exposure may be related to a higher likelihood of the nonglioblastoma subtype.

Dietary phytochemical index in relation to risk of glioma: a case-control study in Iranian adults

Background & aimNo study is available that explores the association of dietary phytochemical index (DPI) with glioma. The objective of the current study was to assess this association in Iranian adults.MethodsThis hospital-based case-control study included 128 newly-diagnosed cases of glioma and 256 age- and sex-matched controls. Data collection on dietary intakes was done using a 123-item validated food frequency questionnaire. Calculation of DPI was done as (dietary energy derived from phytochemical-rich foods (kcal)/total daily energy intake (kcal)) × 100. Logistic regression models were used to examine the association between DPI and glioma.ResultsIndividuals in the top tertile of DPI were more likely to be older and female. Before taking potential confounders into account, subjects in the top tertile of DPI tended to have a 40% reduced chance of glioma than those in the bottom tertile (OR: 0.60; 95% CI: 0.35–1.02, P = 0.06). After controlling for age, sex, energy intake, several demographic variables and dietary intakes, the association between DPI and glioma became strengthened (OR: 0.43; 95% CI: 0.19–0.97, P = 0.04).ConclusionHigh intakes of phytochemical-rich foods were associated with a lower risk of glioma in adults. High consumption of phytochemical-rich foods might be recommended to prevent glioma. However, further studies with a prospective design are needed to confirm our findings.

Coffee and tea consumption and the risk of glioma: a systematic review and dose-response meta-analysis.

In this systematic review and dose-response meta-analysis, we aimed to assess whether coffee and tea consumption is related to the risk of glioma. We performed a systematic literature search using PubMed, Embase, Scopus and the EuropePMC from the inception of database up until 1 October 2020. Exposures in the present study were coffee and tea consumption, the main outcome was the incidence of glioma. The present study compares the association between the exposure of coffee and tea with the incidence of glioma, and the results are reported in relative risks (RR). There are 12 unique studies comprising of 1960731 participants with 2987 glioma cases. Higher coffee consumption was associated with a statistically non-significant trend towards lower risk of glioma (RR 0·77 (95 % CI 0·55, 1·03), P= 0·11; I2:75·27 %). Meta-regression showed that the association between coffee and glioma was reduced by smoking (P= 0·029). Higher tea consumption was associated with a lower risk of glioma (RR 0·84 (95 % CI 0·71, 0·98), P= 0·030; I2:16·42 %). Sensitivity analysis by removal of case-control studies showed that higher coffee consumption (RR 0·85 (95 % CI 0·72, 1·00), P= 0·046; I2:0 %) and higher tea consumption (RR 0·81 (95 % CI 0·70, 0·93), P= 0·004; I2:0 %, Pnon-linearity = 0·140) were associated with lower risk of glioma. Dose-response meta-analysis showed that every one cup of coffee per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 0·99), P= 0·016, Pnon-linearity = 0·054) and every one cup of tea per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 1·00), P= 0·048). This meta-analysis showed apparent association between coffee and tea intake and risk of glioma.

Aspirin, NSAIDs, and Glioma Risk: Original Data from the Glioma International Case-Control Study and a Meta-analysis.

There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or NSAIDs, and results have been conflicting. The purpose of this study was to examine the associations between glioma and aspirin/NSAID use, and to aggregate these findings with prior published studies using meta-analysis. The Glioma International Case-Control Study (GICC) consists of 4,533 glioma cases and 4,171 controls recruited from 2010 to 2013. Interviews were conducted using a standardized questionnaire to obtain information on aspirin/NSAID use. We examined history of regular use for ≥6 months and duration-response. Restricted maximum likelihood meta-regression models were used to aggregate site-specific estimates, and to combine GICC estimates with previously published studies. A history of daily aspirin use for ≥6 months was associated with a 38% lower glioma risk, compared with not having a history of daily use [adjusted meta-OR = 0.62; 95% confidence interval (CI), 0.54-0.70]. There was a significant duration-response trend (P = 1.67 × 10-17), with lower ORs for increasing duration of aspirin use. Duration-response trends were not observed for NSAID use. In the meta-analysis aggregating GICC data with five previous studies, there was a marginally significant association between use of aspirin and glioma (mOR = 0.84; 95% CI, 0.70-1.02), but no association for NSAID use. Our study suggests that aspirin may be associated with a reduced risk of glioma. These results imply that aspirin use may be associated with decreased glioma risk. Further research examining the association between aspirin use and glioma risk is warranted.

Height, waist circumference, body mass index, and body somatotype across the life course and risk of glioma.

Recent studies have suggested height as a risk factor for glioma, but less is known regarding body mass index (BMI) or other anthropomorphic measures. We evaluated the association between body habitus and risk of glioma. We evaluated the association of measures of height, BMI, waist circumference, and somatotypes with risk of glioma in two prospective cohorts, the Nurses' Health Study and the Health Professionals Follow-Up Study. We documented 508 incident cases of glioma (321 glioblastoma [GBM]). In both cohorts, we found no significant association between adult BMI or waist circumference and risk of glioma, with pooled HR for BMI of 1.08 (95% CI 0.85-1.38 comparing ≥ 30 to < 25kg/m2) and for waist circumference of 1.05 (95% CI 0.80-1.37 highest vs. lowest quintile). Higher young adult BMI (at age 18 in NHS and 21 in HPFS) was associated with modestly increased risk of glioma in the pooled cohorts (pooled HR 1.35, 95% CI 1.06-1.72 comparing ≥ 25kg/m2 vs. less; HR 1.34 for women and 1.37 for men). Analysis of body somatotypes suggested reduced risk of glioma among women with heavier body types at all ages this measure was assessed (HRs ranging from 0.52 to 0.65 comparing highest tertile to lowest tertile), but no significant association among men. Height was associated with increased risk of glioma among women (HR 1.09, 95% CI 1.04-1.14 per inch), but not significantly among men. Within the 8 years prior to diagnosis, cases had no material weight loss compared to non-cases. All results were similar when limited to GBM. Adult BMI and waist circumference were not associated with glioma. Higher BMI at age 21 for men and at age 18 for women was modestly associated with risk in the pooled cohort. Based on body somatotypes, however, women with heavier body types during childhood and young adulthood may be at lower risk of glioma, although this association was not observed later in life with measurements of BMI. Greater height was associated with increased risk, and the trend was more pronounced in women.

Abstract 3446: Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of glioma: Results from the Glioma International Case Control Study

Abstract Background: Numerous epidemiologic studies have examined the association between aspirin (ASA), non-steroid anti-inflammatory drugs (NSAIDs) and the development of glioma, but the results have been inconsistent. The goal of this study was to evaluate the relationship between the intake of these drugs and glioma risk in a large, international case-control study. Methods: Between 2010 and 2015, the Glioma International Case-Control Study (GICC) recruited newly diagnosed glioma cases and matched controls in 14 different sites across five countries. Each subject was interviewed using a standardized questionnaire to obtain NSAIDs and ASA use. We examined the associations between ever use (at least &amp;gt; 6 months), duration of drug use and glioma histology. Ever use data on 4533 glioma cases and 4171 controls was combined using maximum likelihood estimation/restricted maximum likelihood meta-analysis methods. Furthermore, based on a priori hypotheses, we performed subgroup analyses based on gender and glioma histological grades. Results: Use of ASA for &amp;gt; 6 months was associated with a 33% lower glioma risk compared to those who never took it (adjusted Meta-OR 0.67, 95% CI 0.54-0.83). Duration of intake showed a significant trend test (p &amp;lt; 0.0001), with ORs became lower for increasing number of years of ASA use. In subgroup analyses, intake of ASA was significantly associated with glioma risk in both men and women (adjusted Meta-OR = 0.65, 95% CI 0.51-0.84 for men; adjusted Meta-OR = 0.74, 95% CI 0.58-0.93 for women). ASA intake was protective for grade IV glioma (glioblastoma) and grade II/III glioma (adjusted meta-OR 0.63, 95% CI 0.5-0.8 for glioblastoma; adjusted meta-OR 0.67, 95% CI 0.50 - 0.89 for grade II/III glioma). For NSAIDs intake, ever use &amp;gt; 6 months was not associated with glioma risk (adjusted meta-OR 0.87, 95% CI 0.71-1.07). However, NSAIDs use was protective for women (adjusted meta-OR 0.72, 95% CI 0.55-0.93) in subgroup analyses but not for men (adjusted meta-OR 1.03; 95% CI 0.86-1.23). The interaction between gender, NSAIDs and glioma risk was significant (p-value 0.0076).. Sensitivity analyses excluding those who took ASA or NSAIDs within the past 12 months for headache, and the removal of proxy respondents did not change our results. Conclusion: ASA was associated with a significant protective effect for glioma, but NSAIDs were only associated with reduced glioma risk in women. Given the possibility of recall bias in case-control studies of brain tumors, we may verify dosage and duration of drug intake in those countries with electronic pharmacy records within the GICC. Citation Format: Rose K. Lai, Renke Zhou, E. Susan Amirian, Christoffer Johansen, Michael E. Scheurer, Georgina N. Armstrong, Ching C. Lau, Elizabeth B. Claus, Jill S. Barnholtz-Sloan, Dora Il’yasova, Joellen Schildkraut, Francis Ali-Osman, Siegal Sadetzki, Richard Houlston, Robert B. Jenkins, Daniel Lachance, Sara H. Olson, Jonine L. Bernstein, Ryan T. Merrell, Margaret R. Wrensch, Faith G. Davis, Sanjay Shete, Christopher I. Amos, Beatrice S. Melin, Melissa Bondy. Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of glioma: Results from the Glioma International Case Control Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3446.

Vacunación universal contra la varicela – Observación sobre ciertos cuestionamientos

In this article, the authors reviewed the current evidences for certain epidemiological observations published recently.In the mentioned publication, the investigator claims that universal varicella vaccination does not reduce varicella burden andincreases the long term risk of glioma by preventing natural infection with varicella zoster virus. The analysis of the evidencesshows that universal vaccination reduces morbidity, mortality, and hospitalization related to varicella. In contrast to investigator’s claim, moreover, the data demonstrate that universal vaccination does induce a herd effect.On the other hand, the available scientific information suggests that the association between natural infection with varicellazoster virus and lower risk of glioma is very weak and does not show causality. In this context one should entertain the idea ofany level of protection against glioma provided by natural infection with varicella zoster virus can be far outweighed by theimpact on morbidity and mortality caused by chickenpox.

History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC).

Varicella zoster virus (VZV) is a neurotropic α‐herpesvirus that causes chickenpox and establishes life‐long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case‐Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two‐stage random‐effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65–0.96). Furthermore, the protective effect of chickenpox was stronger for high‐grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta‐analyses of the literature and investigations of the potential biological mechanism, are warranted.

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study.

Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention.

Highlights of This Issue

Several studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Using data from the Glioma International Case-Control Study (GICC), Amirian and colleagues examined the effects of respiratory allergies and other atopic conditions on glioma risk. The authors report that a history of respiratory allergies was associated with an approximately 30% lower glioma risk. This GICC study further strengthens the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental.Wilson and colleagues evaluated cancer incidence and trends in Appalachia and non-Appalachian regions of the US. Age-adjusted cancer incidence rates were calculated using the most recent data from the United States Cancer Statistics for 2004 to 2011. Generally, Appalachia carries a higher cancer burden compared to non-Appalachia, particularly for tobacco-related cancers. It is important to continue to evaluate this population to better understand behavioral risk factors related to cancer incidence.In this study, Moss and colleagues evaluated the seasonal uptake of human papillomavirus (HPV) vaccine and other adolescent vaccines in the United States. Data came from health care provider–verified vaccination records and seasonal patterns in uptake of HPV and other recommended adolescent vaccines [tetanus, diphtheria, and pertussis (Tdap) booster and meningococcal vaccine]. HPV vaccine initiation (receipt of the first of the three-dose series) data were for female adolescents. HPV vaccine initiation was highest in June, July, and August. These summer peaks are an important opportunity for interventions focused on concomitant vaccination.Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development, and both processes are contributed to by leakage of bacterial lipopolysaccharide (LPS) and flagellin, across the gut barrier. In this study, Kong and colleagues examined associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk. In this prospective study on European populations, the authors found that bacterial exposure levels were positively associated to colorectal cancer risk among men while in women, a possible inverse association may exist.

EPID-01CHICKEN POX AND GLIOMA RISK: PRELIMINARY RESULTS FROM THE GLIOGENE INTERNATIONAL CASE-CONTROL STUDY

The role of viral infections in gliomagenesis has long been in question. Varicella zoster virus (VZV) is a neurotropic alpha-herpesvirus that causes chicken pox among initial infection and shingles upon re-activation later in life. VZV infection has been associated with lower glioma risk in some studies, but several gaps in knowledge remain. Using data from our large consortium, the Glioma International Case-Control Study (GICC), we examined the association between history of chicken pox and glioma risk, overall, by tumor subtype, and by age at glioma diagnosis. Data on 4545 glioma cases and 4173 controls from 14 different sites across five countries was combined using maximum likelihood estimation/restricted maximum likelihood meta-analysis methods. Reporting a positive history of chicken pox was associated with a 21% lower glioma risk, compared to having a negative history of chicken pox (95% CI: 0.65-0.96). When stratified by glioma subtype, a significant protective effect was observed among glioblastoma (GBM) cases (meta-OR: 0.72; 95% CI: 0.55-0.95), but not among the non-GBM group (meta-OR: 0.89; 95% CI: 0.70-1.13). Our findings corroborate previous reports on the protective effect of chicken pox on glioma risk in one of the largest study populations available on this rare and highly fatal disease.

Exogenous and Endogenous Hormones in Relation to Glioma in Women: A Meta-analysis of 11 Case-Control Studies

Background and ObjectivePrevious investigations of glioma risk in women have focused on oral contraceptive (OC), hormone replacement therapy (HRT), and reproductive factors. However, the results of published studies were inconclusive and inconsistent. Thus, a meta-analysis based on published case-control studies was performed to assess the role of exogenous and endogenous hormones factors in glioma risk.MethodsThe PubMed and EMBASE databases were searched without any restrictions on language or publication year. Reference lists from retrieved articles were also reviewed. We included case-control studies reporting relative risks (RRs) with corresponding 95% confidence intervals (CIs) (or data to calculate them) between oral contraceptive (OC) and hormone replacement therapy (HRT) use, reproductive factors and glioma. Random-effects models were used to calculate the summary risk estimates.ResultsFinally, 11 eligible studies with 4860 cases and 14,740 controls were identified. A lower risk of glioma was observed among women who were ever users of exogenous hormones (OC RR = 0.707, 95% CI = 0.604–0.828; HRT: RR = 0.683, 95% CI = 0.577–0.808) compared with never users. An increased glioma risk was associated with older age at menarche (RR = 1.401, 95% CI = 1.052–1.865). No association was observed for menopause status, parous status, age at menopause, or age at first birth and glioma risk.ConclusionThe results of our study support the hypothesis female sex hormones play a role in the development of glioma in women. Additional studies are warranted to validate the conclusion from this meta-analysis and clarity the underlying mechanisms.

Cytotoxicity of glioblastoma cells mediated ex vivo by varicella-zoster virus-specific T cells.

Clinical or laboratory evidence of varicella-zoster virus (VZV) infection has been consistently associated with lower glioma risk in case-control studies, suggesting a protective effect of VZV against glioma. We formulated the following explanatory hypotheses: reactivated VZV preferentially infects and kills gliomas compared to normal parenchyma; and VZV-specific cytotoxic T lymphocytes (CTL) cross-react with gliomas. We established an ex vivo model of VZV infection, which showed that glioma cell lines and primary astrocytes were equally permissive to VZV infection and had similar 15% average decrease in viability upon infection. In co-cultures, the relative growth of glioma cells and astrocytes was not affected by the VZV infection. However, VZV stimulated, but not mock stimulated, peripheral blood mononuclear cells from VZV-seropositive individuals recognized and killed HLA class I-matched glioma cells (mean±SE decrease in viability of 26 ± 12%, p = 0.04), but not matched astrocytes. VZV infection of the glioma cells did not affect the T cell-mediated killing. Taken together, these data suggest that ex vivo VZV infection has similar direct effects on glioma cells and astrocytes. The protective effect of prior VZV infection against the incidence of glioma may be mediated by CTL that recognizes epitopes shared by VZV and glioma cells.

Coffee, Tea, Caffeine Intake, and Risk of Adult Glioma in Three Prospective Cohort Studies

Current data suggest that caffeinated beverages may be associated with lower risk of glioma. Caffeine has different effects on the brain, some of which could play a role in brain carcinogenesis, and coffee has been consistently associated with reduced risk of liver cancer, thus suggesting a potential anticarcinogenic effect. A total of 335 incident cases of gliomas (men, 133; women, 202) were available from three independent cohort studies. Dietary intake was assessed by food frequency questionnaires obtained at baseline and during follow-up. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between consumption of coffee, tea, carbonated beverages, caffeine, and glioma risk adjusting for age and total caloric intake. Estimates from each cohort were pooled using a random-effects model. Consumption of five or more cups of coffee and tea daily compared with no consumption was associated with a decrease risk of glioma (RR, 0.60; 95% CI, 0.41-0.87; P(trend) = 0.04). Inverse, although weaker, associations were also observed between coffee, caffeinated coffee, tea, and carbonated beverages and glioma risk. No association was observed between decaffeinated coffee and glioma risk. Among men, a statistically significant inverse association was observed between caffeine consumption and risk of glioma (RR, 0.46; 95% CI, 0.26-0.81; P(trend) = 0.03); the association was weaker among women. Our findings suggest that consumption of caffeinated beverages, including coffee and tea, may reduce the risk of adult glioma, but further research is warranted to confirm these findings in other populations.

Reproductive and hormonal factors and risk of brain tumors in adult females

Causes of brain tumors are largely unknown, and there is an urgent need to identify possible risk factors. Several observations point to a possible role of reproductive hormones, but few epidemiologic studies have examined whether reproductive factors, such as age at menarche and parity, are associated with brain tumor risk. We conducted a multi-center case-control study of newly diagnosed glioma (n = 212) and meningioma (n = 151) and frequency-matched controls (n = 436) in women from hospitals in Phoenix, Arizona; Boston, Massachusetts; and Pittsburgh, Pennsylvania between 1994 and 1998. Research nurses interviewed patients regarding potential risk factors for brain tumors, including reproductive factors and hormone use. Unconditional logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Risk of glioma increased with older age at menarche [OR = 1.90 (95% CI = 1.09-3.32) for age at menarche > or =14 vs. <12 years]. Early age at first birth was associated with reduced risk of glioma [OR = 0.43 (95% CI = 0.23-0.83) for a first birth before age 20 vs. nulliparity], but there was little effect of number of births. Exogenous hormone use was also associated with a lower risk of glioma, but risks did not vary systematically according to duration of use or age at first use. Possibly owing to low statistical power, there were few noteworthy associations between meningioma and reproductive factors, other than a nonsignificant (p = 0.09) trend of increasing risk with increasing age at menopause. The findings suggest that hormonal exposures early in life may be associated with risk of glioma, but the evidence is inconsistent and does not point clearly to a specific causal or protective hypothesis.