Selected human leukocyte antigen class II polymorphisms and risk of adult glioma.

Few studies have examined the relationship between human leukocyte antigen (HLA) polymorphisms and adult glioma, particularly at class II loci. We evaluated the association between selected HLA class II polymorphisms and adult glioma in a large, hospital-based case-control study, using unconditional logistic regression. DQB1 06 (OR=1.67, 95% CI=1.17-2.39) and DRB1 13 (OR=1.69, 95% CI=1.08-2.64) alleles were associated with an increased risk of glioma, while the DQB1 05 allele showed an inverse association (OR=0.63, 95% CI=0.43-0.93). These results, which were of borderline significance once controlled for the false discovery rate, suggest a potential role for the DQB1 06, DQB1 05, and DRB1 13 alleles in glioma susceptibility.

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 exposure to magnetic fields and the risk of brain tumors.

We investigated the association between occupational exposure to extremely low-frequency magnetic fields (MFs) and the risk of glioma and meningioma. Occupational exposure to MF was assessed for 489 glioma cases, 197 meningioma cases, and 799 controls enrolled in a hospital-based case-control study. Lifetime occupational history questionnaires were administered to all subjects; for 24% of jobs, these were supplemented with job-specific questionnaires, or "job modules," to obtain information on the use of electrically powered tools or equipment at work. Job-specific quantitative estimates for exposure to MF in milligauss were assigned using a previously published job exposure matrix (JEM) with modification based on the job modules. Jobs were categorized as < or =1.5 mG, >1.5 to <3.0 mG, and > or =3.0 mG. Four exposure metrics were evaluated: (1) maximum exposed job; (2) total years of exposure >1.5 mG; (3) cumulative lifetime exposure; and (4) average lifetime exposure. Odds ratios (ORs) were calculated using unconditional logistic regression with adjustment for the age, gender, and hospital site. The job modules increased the number of jobs with exposure > or =3.0 mG from 4% to 7% relative to the JEM. No statistically significant elevation in ORs or trends in ORs across exposure categories was observed using four different exposure metrics for the three tumor types analyzed. Occupational exposure to MFs assessed using job modules was not associated with an increase in the risk for glioma, glioblastoma, or meningioma among the subjects evaluated in this study.

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.

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.

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.

Personal hair dye use and risks of glioma, meningioma, and acoustic neuroma among adults.

Previous studies have suggested an association of personal hair dye use with bladder and hematopoietic cancers. Risks for brain tumors are not well understood. The authors investigated associations between use of synthetic hair dyes and risk of brain tumors in a hospital-based case-control study. The study included adults newly diagnosed with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) between 1994 and 1998 at three urban US hospitals and 799 controls. Odds ratios were estimated and 95% confidence intervals were calculated using unconditional logistic regression. Detailed exposure histories were obtained by interview. There was no consistent pattern of elevated odds ratios for glioma, meningioma, or acoustic neuroma with use or prolonged use of permanent, semipermanent, temporary, or gradual hair dyes. Although use of permanent brown hair dye for 20 or more years was associated with glioma among women, the estimate was imprecise (odds ratio = 3.8, 95% confidence interval: 1.2, 12.5) and was based on just 13 exposed cases; thus, this could be a chance finding. Overall, there was little consistent evidence for an association of synthetic hair dye use with glioma, meningioma, or acoustic neuroma. However, prolonged use of dark-colored permanent dyes warrants further investigation given the high prevalence of hair dyeing.

Lead, genetic susceptibility, and risk of adult brain tumors.

BACKGROUND: Although few etiologic factors for brain tumors have been identified, limited data suggest that lead may increase the risk of brain tumors, particularly meningioma. The ALAD G177C polymorphism affects the toxicokinetics of lead and may confer genetic susceptibility to adverse effects of lead exposure. METHODS: We examined occupational exposure to lead and risk of brain tumors in a multisite, hospital-based, case-control study of 489 patients with glioma, 197 with meningioma, and 799 non-cancer controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to hospital. ALAD genotype was assessed by a Taqman assay for 355 glioma patients, 151 meningioma patients, and 505 controls. Exposure to lead was estimated using a rigorous questionnaire-based exposure assessment strategy incorporating lead measurement and other occupational data abstracted from published articles and reports. RESULTS: Increased risk of meningioma with occupational lead exposure (estimated by odds ratios and 95% confidence intervals) was most apparent in individuals with the ALAD2 variant allele, for whom risk increased from 1.1 (0.3-4.5) to 5.6 (0.7-45.5) and 12.8 (1.4-120.8) for estimated cumulative lead exposures of 1 to 49 microg/m3-y, 50 to 99 microg/m3-y, and >or=100 microg/m3-y, respectively, compared with unexposed individuals (two-sided P trend = 0.06). This relationship became stronger after excluding occupational lead exposures characterized by a low confidence level or occurring in the 10 years before meningioma diagnosis. Occupational lead exposure was not associated with glioma risk. CONCLUSIONS: Although our results indicate that lead may be implicated in meningioma risk in genetically susceptible individuals, these results need to be interpreted with caution given the small numbers of exposed cases with a variant genotype.

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.

Delta-aminolevulinic acid dehydratase polymorphism and risk of brain tumors in adults.

The enzyme delta-aminolevulinic acid dehydratase (ALAD), which catalyzes the second step of heme synthesis, can be inhibited by several chemicals, including lead, a potential risk factor for brain tumors, particularly meningioma. In this study we examined whether the ALAD G177C polymorphism in the gene coding for ALAD is associated with risk of intracranial tumors of the brain and nervous system. We use data from a case-control study with 782 incident brain tumor cases and 799 controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to the hospital. Blood samples were drawn and DNA subsequently sent for genotyping for 73% of subjects. ALAD genotype was determined for 94% of these samples (355 glioma, 151 meningioma, 67 acoustic neuroma, and 505 controls). Having one or more copy of the ALAD2 allele was associated with increased risk for meningioma [odds ratio (OR) = 1.6; 95% confidence interval (CI), 1.0-2.6], with the association appearing stronger in males (OR = 3.5; 95% CI, 1.3-9.2) than in females (OR = 1.2; 95% CI, 0.7-2.2). No increased risk associated with the ALAD2 variant was observed for glioma or acoustic neuroma. These findings suggest that the ALAD2 allele may increase genetic susceptibility to meningioma.

Self-reported electrical appliance use and risk of adult brain tumors.

Electrical appliances produce the highest intensity exposures to residential extremely low frequency electromagnetic fields. The authors investigated whether appliances may be associated with adult brain tumors in a hospital-based case-control study at three centers in the United States from 1994 to 1998. A total of 410 glioma, 178 meningioma, and 90 acoustic neuroma cases and 686 controls responded to a self-administered questionnaire about 14 electrical appliances. There was little evidence of association between brain tumors and curling iron, heating pad, vibrating massager, electric blanket, heated water bed, sound system, computer, television, humidifier, microwave oven, and electric stove. Ever use of hair dryers was associated with glioma (odds ratio = 1.7, 95% confidence interval: 1.1, 2.5), but there was no evidence of increasing risk with increasing amount of use. In men, meningioma was associated with electric shaver use (odds ratio = 10.9, 95% confidence interval: 2.3, 50), and odds ratios increased with cumulative minutes of use, although they were based on only two nonexposed cases. Recall bias for appliances used regularly near the head or chance may provide an alternative explanation for the observed associations. Overall, results indicate that extremely low frequency electromagnetic fields from commonly used household appliances are unlikely to increase the risk of brain tumors.

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.

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.

Occupation and risk of meningioma and acoustic neuroma in the United States.

BACKGROUND: Workplace exposures may be related to the development of brain tumors. In this case-control study, we examine occupation as a risk factor for meningioma and acoustic neuroma. METHODS: A lifetime work history was obtained for 197 incident cases of meningioma, 96 cases of acoustic neuroma and 799 controls with non-malignant diseases enrolled from three hospitals in the United States between 1994 and 1998. Jobs considered to have similar tasks and chemical exposures were assigned to an occupational group. Logistic regression was used to estimate odds ratios (OR) adjusted for study matching factors (hospital, age, sex, race/ethnicity, and proximity of residence to the hospital) and education. RESULTS: Elevated risk of meningioma was observed for individuals who had ever worked in the following occupational groups: auto body painters, designers and decorators, military occupations, industrial production supervisors, teachers, and managers. For acoustic neuroma, increased risk was noted for having worked as an athlete, gas station attendant, purchasing agent, sales representative, or teacher. CONCLUSIONS: Although limited by multiple comparisons and the relatively small number of cases and controls in many occupational groups, these results nevertheless provide clues that deserve additional study in future epidemiologic studies.

Cancer in first-degree relatives and risk of glioma in adults.

Relatively few studies have examined glioma risk in relation to history of cancer in first-degree relatives. We sought to describe such risks in a large hospital-based case-control study. Histologically confirmed incident adult glioma cases (n = 489) were identified at three regional referral hospitals between June 1994 and August 1998. Controls (n = 799) admitted to the same hospitals for nonmalignant conditions were frequency-matched on age, sex, race/ethnicity, hospital, and proximity of residence to hospital. Participants received a personal interview, including questions regarding cancer in family members. Odds ratios (ORs) were calculated to estimate the risk of glioma associated with a history of cancer in a first-degree relative using conditional logistic regression and compared with standardized incidence ratios among relatives of cases versus relatives of controls. Among participants reporting a family history of a brain cancer or a brain tumor, risk of glioma was 1.6 [95% confidence interval (CI), 0.5-5.3; n = 5] and 3.0 (95% CI, 0.9-10.8; n = 7), respectively, in comparison with those without such family histories. Participants who had a family history of stomach (OR, 2.2; 95% CI, 1.0-4.6), colon (OR, 1.4; 95% CI, 0.9-2.2), or prostate cancer (OR, 2.1; 95% CI, 1.1-3.8) or Hodgkin disease (OR, 2.4; 95% CI, 0.9-6.3) had an increased glioma risk. OR estimates were similar to the ratios of standardized incidence ratios for cancer in relatives of cases versus controls. Shared environmental or genetic factors in families may influence glioma risk. Our findings suggest that individuals with a family history of specific cancers other than glioma may have an increased glioma risk.

Sociodemographic indicators and risk of brain tumours.

BACKGROUND: To better understand patterns of occurrence or diagnosis of brain tumours in different segments of the population, we evaluated associations between sociodemographic variables and the relative incidence of brain tumours as part of a multi-faceted case-control study. METHODS: The study was conducted at hospitals in three US cities between 1994 and 1998. In all, 489 glioma cases (354 high-grade, 135 low-grade), 197 meningioma cases, 96 acoustic neuroma cases, and 799 controls admitted to the same hospitals for any of a variety of non-neoplastic diseases or conditions were enrolled and interviewed. Logistic regression was used to estimate odds ratios (OR), calculate 95% CI, and test for trends. RESULTS: The OR showed significant positive associations with household income for low-grade glioma, meningioma, and acoustic neuroma, but not for high-grade glioma. Positive associations were observed with level of education for low-grade glioma and acoustic neuroma, but not for high-grade glioma or meningioma. Jewish religion was associated with a significantly elevated risk for meningioma (OR = 4.3; 95% CI: 2.0-9.0). Being single at the time of tumour diagnosis or enrolment was associated with significantly reduced risks for meningioma (OR = 0.4; 95% CI: 0.3-0.6) and low- or high-grade glioma (OR = 0.6; 95% CI: 0.5-0.8), but not for acoustic neuroma. CONCLUSIONS: Associations with sociodemographic variables varied considerably among the different subtypes of brain tumour, including between low-grade and high-grade glioma. The general pattern was for associations with indicators of affluence and education to be stronger for tumours that tend to grow more slowly and have less catastrophic effects, although the evidence was mixed for meningioma. We cannot isolate the specific factors underlying the observed associations, but intrapopulation differences in the completeness or timing of diagnosis may have played a role. There is less opportunity for such influences to operate for the rapidly progressing, high-grade gliomas than for more slowly growing tumours.

Laterality of brain tumors.

Tumor laterality was evaluated with respect to presenting symptoms and demographic factors among 489 adults with histologically confirmed glioma (354 high-grade, 135 low-grade), 197 with meningioma, and 96 with acoustic neuroma. The ratio of left-sided to right-sided tumors did not differ significantly from 1.00 for any of the major tumor types. Low-grade glioma and meningioma occurred nonsignificantly more often on the left side, whereas high-grade glioma and acoustic neuroma occurred nonsignificantly more often on the right side. Aphasia or mental status changes were significantly more common among glioma patients with tumors on the left side than among those with tumors on the right side. Associations between tumor laterality and symptoms may influence the probability or timing of diagnosis, possibly differentially by marital status.

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.

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.