Contacts with animals and humans as risk factors for adult brain tumours. An international case-control study

While numerous studies have addressed the possible role of farming and related exposures as risk factors for brain tumours in adults, few of them have examined the potential effect of exposure to farm animals or pets. In an international multicentre case-control study, we investigated whether residence on a farm, contact with animals, or working in occupations with a high degree of potential contact with animals or humans were associated with brain tumours. Using a common questionnaire, 1177 cases of glioma, 330 with meningioma and 2478 controls from eight centres were interviewed about the exposures and, in particular, about their contacts with nine species of animals: dairy cattle, beef cattle, pigs, horses, sheep, goats, poultry, dogs and cats. Living or working on a farm was not a risk factor, for either glioma or meningioma. Except in some centres, there was no relationship between having contacts with farm animals or pets and the risk of brain tumour, for either type of tumour or either sex. In relation to seven industrial groups involving frequent human and/or animal contacts, no association was apparent for either glioma or meningioma. In relation to 25 occupational groups with potential frequent contact with humans and/or animals, for glioma there was a reduced risk for biological technicians (Odds Ratio (OR)/=0, P=0.01), and general farm workers (OR=0.66, 95% Confidence Interval (CI): 0.5-0.9). For meningioma, there was an increased risk for cooks (OR=2.0; CI: 1.2-3.4). With some exceptions, these results indicate no association between either the type of brain tumour and contacts with animals, or with occupations that include a high level of contact with animals or a high level of contact with humans.     

Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review

Although exposure to moderate-to-high doses of ionizing radiation is the only established environmental risk factor for brain and CNS tumors, it is not clear whether this relationship differs across tumor subtypes, by sex or age at exposure, or at the low-to-moderate range of exposure. This systematic review summarizes the epidemiologic evidence on the association between ionizing radiation exposure and risk of brain/CNS tumors. Articles included in this review estimated radiation exposure doses to the brain and reported excess relative risk (ERR) estimates for brain/CNS tumors. Eight cohorts were eligible for inclusion in the analysis. Average age at exposure ranged from 8 months to 26 years. Mean dose to the brain ranged from 0.07 to 10 Gy. Elevated risks for brain/CNS tumors were consistently observed in relation to ionizing radiation exposure, but the strength of this association varied across cohorts. Generally, ionizing radiation was more strongly associated with risk for meningioma compared with glioma. The positive association between ionizing radiation exposure and risk for glioma was stronger for younger vs older ages at exposure. We did not observe an effect modification on the risk for meningioma by sex, age at exposure, time since exposure, or attained age. The etiologic role of ionizing radiation in the development of brain/CNS tumors needs to be clarified further through additional studies that quantify the association between ionizing radiation and risk for brain/CNS tumors at low-to-moderate doses, examine risks across tumor subtypes, and account for potential effect modifiers.     

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.     

Genetic polymorphisms in GSTM1, -P1, -T1, and CYP2E1 and the risk of adult brain tumors.

GST and CYP2E1 genes are involved in metabolism of several compounds (e.g., solvents) that may play a role in brain cancer etiology. We evaluated associations between polymorphisms in these genes and adult brain tumor incidence. Cases were 782 patients with brain tumors diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples that had been collected from 1277 subjects (80% of all subjects; 604 controls; 422 gliomas, 172 meningiomas, and 79 acoustic neuromas), and genotyping was successfully conducted for GSTM1 null, GSTT1 null, GSTP I105V, GSTP A114V, CYP2E1 RsaI, and CYP2E1 Ins96. The GSTP1 105 Val/Val genotype was associated with increased glioma incidence [odds ratio (OR), 1.8; 95% confidence limits (CLs), 1.2, 2.7], with the estimated effect following a trend of increasing magnitude by number of variant alleles (Ile/Ile: OR, 1.0; Ile/Val: OR, 1.3; Val/Val: OR, 2.1). The CYP2E1 RsaI variant was weakly associated with glioma (OR, 1.4; 95% CL, 0.9, 2.4) and acoustic neuroma (OR, 2.3; 95% CL, 1.0, 5.3), with some indication of stronger associations among younger subjects. Estimated effects of the gene variants differed by glioma subtype. There was evidence of supermultiplicativity of the joint effect of GSTP1 I105V and CYP2E1 RsaI variants on both glioma and acoustic neuroma, even following adjustment of estimates toward a common prior distribution using hierarchical regression models. Previously reported associations between the GSTT1 null genotype and overall glioma incidence were not replicated, but an association with meningioma was observed (OR, 1.5; 95% CL, 1.0, 2.3). These findings may provide clues to both genetic and environmental determinants of brain tumors.     

XRCC1 and XRCC3 variants and risk of glioma and meningioma

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.     

DNA repair gene polymorphisms and risk of adult meningioma,glioma, and acoustic neuroma

Although the etiology of primary brain tumors is largely unknown, prior studies suggest that DNA repair polymorphisms may influence risk of glioma. Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma, but these tumors have not been well studied. We estimated the risk of glioma (n = 362), meningioma (n = 134), and acoustic neuroma (n = 69) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based, case–control study conducted by the National Cancer Institute. We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 (OR_CT/TT = 3.5; 95% confidence interval: 1.8–6.9; P_trend .0006), which persisted after controlling for multiple comparisons (P = .019). Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 (P_trend .01); MUTYH rs3219466 (P_trend .02), and PCNA rs25406 (P_trend .03). The NBN rs1805794 minor allele variant was associated with decreased meningioma risk (P_trend .006). Risk of acoustic neuroma was increased for the ERCC2 rs1799793 (P_trend .03) and ERCC5 rs17655 (P_trend .05) variants and decreased for the PARP1 rs1136410 (P_trend .03). Decreased glioma risk was observed with the XRCC1 rs1799782 variant (P_trend .04). Our results suggest that common DNA repair variants may affect the risk of adult brain tumors, especially meningioma.     

Occupational and residential exposure to electromagnetic fields and risk of brain tumors in adults: a case-control study in Gironde, France

The etiology of brain tumors remains largely unknown. Among potential risk factors, exposure to electromagnetic fields is suspected. We analyzed the relationship between residential and occupational exposure to electromagnetic field and brain tumors in adults. A case-control study was carried out in southwestern France between May 1999 and April 2001. A total of 221 central nervous system tumors (105 gliomas, 67 meningiomas, 33 neurinomas and 16 others) and 442 individually age- and sex-matched controls selected from general population were included. Electromagnetic field exposure [extremely low frequency (ELF) and radiofrequency separately was assessed in occupational settings through expert judgement based on complete job calendar, and at home by assessing the distance to power lines with the help of a geographical information system. Confounders such as education, use of home pesticide, residency in a rural area and occupational exposure to chemicals were taken into account. Separate analyses were performed for gliomas, meningiomas and acoustic neurinomas. A nonsignificant increase in risk was found for occupational exposure to electromagnetic fields [odds ratio (OR = 1.52, 0.92-2.51)]. This increase became significant for meningiomas, especially when considering ELF separately [OR = 3.02; 95 percent confidence interval (95% CI) =1.10-8.25]. The risk of meningioma was also higher in subjects living in the vicinity of power lines (<100 m), even if not significant (OR = 2.99, 95% CI 0.86-10.40). These data suggest that occupational or residential exposure to ELF may play a role in the occurrence of meningioma.     

Association of Single Nucleotide Polymorphisms (SNPs) in Genes Encoding for Folate Metabolising Enzymes with Glioma and Meningioma in Indian Population

Background: The association of primary brain tumors with Single Nucleotide polymorphisms (SNPs) in genes offolate metabolising enzymes have been reported to vary among different ethnic population. Here, we have studied theassociation of SNPs of folate metabolizing genes with the primary brain tumors (glioma and meningioma) in North Indianpopulation. Methods: SNPs of genes coding for folate metabolizing enzymes was carried out in 288 study populationfrom North India [Glioma (n=108), Meningioma (n=76) and healthy-control (n=104)]. The allele-specific polymerasechain reaction (ARMS-PCR) was used to analyse the SNP A1298C of the MTHFR (Methylenetetrahydrofolate-reductase)and the SNP A66G of the methionine synthase reductase (MTRR) genes. The PCR-RLFP (Restriction Fragment LengthPolymorphism) was used to analyse the SNP C677T of the Methylene tetrahydrofolate-reductase and the SNP A2756Gof the methionine-synthase (MTR) genes. Serum homocysteine, vitamin B12 and folate levels were evaluated in controls/patients serum using Chemiluminescence immunoassay and the levels were correlated with SNPs genotype. Results:The CC genotype of MTHFR A1298C was observed to have reduced risk of having meningioma than AA genotype(odd ratio=0.62, 95%CI 0.32-0.97, p=0.03). Similarly, the AG genotype of MTRR A66G showed reduced risk ofglioma than AA genotype (odd ratio=0.56, 95%CI 0.32-0.97, p=0.039). Furthermore, in patients with AA genotype ofMTR A2756G and CT genotype of MTHFR C677T showed higher serum homocysteine level than GG genotype (8.6μmol/L, p=0.048) and CC genotype (11.2μmol/L, p=0.039) respectively. Conclusion: Our findings provide an insightinto the risk association of SNPs in MTHFR A1298C and MTRR A66G genes with glioma/meningioma patients.Further studies are needed to evaluate their clinical implications.     

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.     

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.     

Oxidative response gene polymorphisms and risk of adult brain tumors

Oxidative stress is believed to play a key role in tumor formation. Although this mechanism could be especially pertinent for brain tumors given the high oxygen consumption of the brain, very little has been published regarding brain tumor risk with respect to genes mediating oxidative stress. Using data from non-Hispanic whites in a hospital-based case-control study conducted by the National Cancer Institute between 1994 and 1998, we evaluated risk of glioma (n=362), meningioma (n=134), and acoustic neuroma (n=69) compared to noncancer controls (n=494) with respect to nine single nucleotide polymorphisms from seven genes involved in oxidative stress response (CAT, GPX1, NOS3, PON1, SOD1, SOD2, and SOD3). We observed increased risk of glioma (odds ratio [OR](CT/CC)=1.3; 95% confidence interval [95% CI], 1.0-1.7) and meningioma (OR(CT/CC)=1.7; 95% CI, 1.1-2.7) with the C variant of SOD3 rs699473. There was also indication of increased acoustic neuroma risk with the SOD2 rs4880 Ala variant (OR(CT/CC)=2.0; 95% CI, 1.0-4.2) and decreased acoustic neuroma risk with the CAT rs1001179 T allele variant (OR(CT/TT)=0.6; 95% CI, 0.3-1.0). These relationships persisted when major groups of disease controls were excluded from the analysis. Our results suggest that common variants in the SOD2, SOD3, and CAT genes may influence brain tumor risk.     

Reproductive factors and the risk of brain tumors: A population-based study in Sweden

Possible associations between childbearing and the risk of brain cancer were explored in a case-control study “nested” within a large nationwide cohort defined by the Swedish Fertility Registry. Among women born between 1925–1975, 1,088 patients with meningiomas and 1,657 patients with gliomas were identified in the Swedish Cancer Registry. For every woman diagnosed with brain tumor, 5 age-matched controls were selected among those in the Fertility Registry. Relative risks were estimated by odds ratios from conditional logistic regression. Ever-parous women were at a reduced risk of glioma compared to nulliparous women, while parity was unrelated to meningioma risk. Age at first birth was unrelated to both meningioma and glioma risk. The gradient in risk between ever-parous and nulliparous women for gliomas, but not meningiomas, is difficult to explain biologically. A possible explanation is that pregnancy-induced alterations in androgen levels reduce the risk of glioma in parous women. Alternatively, childlessness may represent a marker of an occult glioma, negatively affecting fecundity. Overall, our present results do not support the notion that hormonal changes, or other physiological changes induced by childbearing, play an important role in the development of brain tumors. Int. J. Cancer 72:389–393, 1997. © 1997 Wiley-Liss, Inc.     

Occupation, exposure to polycyclic aromatic hydrocarbons and laryngeal cancer risk

Primary risk factors for laryngeal cancer are smoking and alcohol. The relevance of occupational exposures in the etiology of laryngeal cancer is not yet clarified. Some studies have suggested various occupational agents as additional causal risk factors. A population-based case-control study 1:3 frequency matched by age and gender on laryngeal cancer was carried out in southwest Germany with 257 cases (236 males and 21 females between the ages of 37-80, histologically confirmed and diagnosed between January 5, 1998 and December 31, 2000) and 769 population controls (702 males, 67 females). Occupational exposures and other risk factors were obtained with face-to-face interviews using a detailed standardized questionnaire. The complete individual work history was assessed. A detailed assessment of work conditions was obtained by job-specific questionnaires for selected jobs known to be associated with exposure to potential carcinogens. A specific substance list was used as second method for exposure assessment. Blood samples were taken from all individuals for genotype analysis. A strong effect of polycyclic aromatic hydrocarbons exposure on laryngeal cancer risk after adjustment for smoking and alcohol (odds ratio [OR] = 5.2, 95% confidence interval [CI] = 1.6-17.1) was observed for concordant exposure classified with both methods, and a clear dose-response (p < 0.01 for linear trend) for exposure duration. Our findings are supported by risks associated with occupational groups in which this exposure is a priori considered likely. A differential effect by glutathione-S-transferases-M1 genotype was found, however, small numbers do not allow firm conclusions on effect modification. Our study contributes to classifying polycyclic aromatic hydrocarbons as a risk factor for laryngeal cancer.     

Risk factors for tumors of the brain and meninges: results from the Adelaide Adult Brain Tumor Study.

A population-based case-control study of incident primary brain tumors in adults was carried out in Adelaide, Australia in the period 1987 through 1990. It included 110 subjects with newly diagnosed primary glioma, 60 subjects with meningioma and 417 controls selected from the Australian Electoral Roll and frequency-matched to cases for age (within 2 years), sex and postal code. Some interesting new associations were found: (1) an increased risk of glioma in women who reported working with cathode-ray tubes (relative risk = 4.1, 95% confidence interval: 1.3-13.2); (2) a decreased risk of glioma in those with a history of allergic diseases (relative risk = 0.5, 95% confidence interval: 0.3-0.9); and (3) an increased risk of meningioma in those exposed to passive smoking from a spouse, especially amongst females (relative risk = 2.7, 95% confidence interval: 1.2-6.1). A pooled analysis of the multi-center group of studies to which the present study belongs should allow more confident claims concerning risk factors for brain tumors.     

Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms

This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. To follow-up on a previous report by Buzio et al., we also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides [odds ratio (OR): 1.60; 95% confidence interval (CI): 1.00-2.55]. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele (OR: 4.00; 95% CI: 1.55-10.33) but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles (P-interaction: 0.04). Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes (OR: 6.47; 95% CI: 1.82-23.00; P-interaction: 0.02) compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, we observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.     

Parental occupational exposure to pesticides,animals and organic dust and risk of childhood leukemia and central nervous system tumors: Findings from the International Childhood Cancer Cohort Consortium (I4C)

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case–control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97–10.68; insecticides HR = 2.86, 95% CI = 0.99–8.23; animals HR = 3.89, 95% CI = 1.18–12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12–5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31–0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.     

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.     

Serum Levels of APRIL Increase in Patients with Glioma,Meningioma and Schwannoma

Objective: Brain tumors are of high mortality and morbidity for which there is still no cure. The TNF family cytokine,A Proliferation Inducing Ligand (APRIL), is shown to help proliferation and development of tumor cells. We assessedserum levels of APRIL in patients with glioma, meningioma and schwannoma in comparison to healthy individuals.Methods: Peripheral blood samples of 68 patients with brain tumors, divided into three groups of gliomas (n=25),meningiomas (n=30) and schwannomas (n=13), as well as 45 healthy individuals were obtained. Serum samples wereprepared and stored in -40°C until usage. Using a commercial ELISA method, APRIL concentration was measured ineach serum sample. The obtained data were then analyzed using SPSS software. Results: APRIL serum levels werehigher in all patients compared to the controls (P<0.001). Moreover, APRIL serum levels were higher in each of thetumor bearing groups (gliomas, meningiomas and schwannomas) in comparison to the controls (P<0.001, <0.001and =0.001, respectively). Comparing APRIL between the patients groups showed no significant difference. Age andgender showed no significant correlation with serum APRIL levels, although the age of patients in glioma group wassignificantly lower than controls (P=0.017). The serum APRIL levels in gliomas with histological grade showed nodifference, but in meningiomas, it was lower in tumors with higher grades (P= 0.011). Conclusion: Increased serumlevels of APRIL in patients with meningioma and schwannoma as well as glioma may indicate a common role of thiscytokine in brain tumors.     

Parental occupation, occupational exposure to solvents and polycyclic aromatic hydrocarbons and risk of childhood brain tumors (Italy, France, Spain)

The role of parental occupational exposure in childhood brain tumorswas investigated in a population-based case-control study grouping 251 casesand 601 controls from three European centers: Milan (Italy), Paris (France),and Valencia (Spain). Parental occupational exposure to solvents andpolycyclic aromatic hydrocarbons (PAH) during the five-year period beforebirth was estimated using a job-exposure matrix developed earlier in the samecountries. Odds ratios (OR) of brain tumors for each occupation andoccupational exposure were estimated by logistic regression, adjusting forchilds age, gender, exposure to tobacco smoke and ionizing radiation,mothers age and years of schooling, and center. The risk of childhood braintumors rose when fathers worked in agriculture (OR = 2.2, 95 percentconfidence interval [CI] = 1.0-4.7) and motor-vehicle-related occupations. Inthe latter group, the risk increased for primitive neuroectodermal tumors inparticular (OR = 2.7, CI = 1.1-6. 6). Astroglial tumors were more frequentamong children of mothers in health services (OR = 2.2, CI = 1.0-4.9).Paternal exposure to PAHs was associated with an increased, but notdose-related, risk of primitive neuroectodermal tumors (OR = 2.0, CI =1.0-4.0), and maternal exposure to solvents at a high level was associatedwith an increased risk of both astroglial (OR = 2.3, CI = 0.9-5.8) andprimitive neuroectodermal tumors (OR = 3.2, CI = 1.0-10.3).     

Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors

Genes involved in phase I and phase II regulation of aromatic hydrocarbon-induced effects exhibit sequence variability that may mediate the risk of adult brain tumors. We evaluated associations between gene variants in CYP1A1, CYP1B1, GSTM3, EPHX1, and NQO1 and adult brain tumor incidence. Cases were patients with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) diagnosed from 1994 to 1998 at three U.S. hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples collected from 1277 subjects, and genotyping was conducted for CYP1A1 I462V, CYP1B1 V432L, EPHX1 Y113H, GSTM3 *A/*B (intron 6 deletion), and NQO1 P187S. The CYP1B1 V432L homozygous variant was associated with decreased risk of meningioma (odds ratio [OR] = 0.6; 95% CI, 0.3-1.0) but not the other tumor types. The GSTM3 *B/*B genotype was associated with increased risk of glioma (OR = 2.3; 95% CI, 1.0-5.2) and meningioma (OR = 3.6; 95% CI, 1.3-9.8). Increased risks associated with GSTM3 *B/*B were observed in younger subjects (age < 50) and older subjects (age > or = 50), in men and women, and within each study site. The magnitude of association for GSTM3 with glioma and meningioma was greater among ever-smokers than among those who had never smoked. None of the other genotypes showed consistent associations with any tumor type. The association with the GSTM3 *B allele, while intriguing, requires replication, and additional research is needed to clarify the function of the GSTM3 alleles studied here.