Risk Factors for Gliomas and Meningiomas in Males in Los Angeles County1

Home , Fibrillary astrocytoma, Glioma, Meningioma

[CANCER RESEARCH 49, 6137-6143. November 1, 1989] Risk Factors for Gliomas and Meningiomas in Males in Los Angeles County1

Susan Preston-Martin,2 Wendy Mack, and Brian E. Henderson

Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, California 90033

ABSTRACT views with proxy respondents, we were unable to include a large proportion of otherwise eligible cases because they were deceased or Detailed job histories and information about other suspected risk were too ill or impaired to participate in an interview. The Los Angeles factors were obtained during interviews with 272 men aged 25-69 with a County Cancer Surveillance Program identified the cases (26). All primary brain tumor first diagnosed during 1980-1984 and with 272 diagnoses had been microscopically confirmed. individually matched neighbor controls. Separate analyses were con A total of 478 patients were identified. The hospital and attending ducted for the 202 glioma pairs and the 70 meningioma pairs. Meningi- physician granted us permission to contact 396 (83%) patients. We oma, but not glioma, was related to having a serious head injury 20 or were unable to locate 22 patients, 38 chose not to participate, and 60 more years before diagnosis (odds ratio (OR) = 2.3; 95% confidence were aphasie or too ill to complete the interview. We interviewed 277 interval (CI) = 1.1-5.4), and a clear dose-response effect was observed patients (74% of the 374 patients contacted about the study or 58% of relating meningioma risk to number of serious head injuries (/' for trend the initial 478 patients). An additional 161 patients who were otherwise = 0.01; OR for > 3 injuries = 6.2; CI = 1.2-31.7). Frequency of full- eligible were deceased, only 10 of these were meningioma patients. mouth dental X-ray examinations after age 25 related to both glioma (/' Controls. We sought a neighborhood control for each of these 277 for trend = 0.04) and meningioma risk (/' for trend = 0.06). Glioma, but patients by use of a procedure that defines a sequence of houses on not meningioma risk, related to duration of prior employment in jobs specified neighborhood blocks. Our goal was to interview the first male likely to involve high exposure to electric and magnetic fields (P for trend resident in the sequence who corresponded to the patient in race and = 0.05). This risk was greatest for astrocytoma (OR for employment in age (birth year within 5 years of birth year of the patient). We would such jobs for > 5 years = 4.3; CI = 1.2-15.6). More glioma cases had not interview a match until we ascertained that there were no available worked in the rubber industry (discordant pairs 6/1) and more worked in matches at houses visited earlier in the sequence. If no one was home hot processes using plastics (9/1). More meningioma cases had jobs that at the time of the visit, we left a return envelope, an explanatory letter involved exposure to metal dusts and fumes (discordant pairs 13/5), and and a brief questionnaire about the age, sex and race of household six of these cases and two controls worked as machinists. Finally, there members at the residence and made a follow-up visit after several days. was a protective effect among glioma pairs relating to frequency of use In 210 instances, the first appropriate person agreed to be interviewed. of vitamin C and other vitamin supplements (P for trend = 0.004); the In 62 neighborhoods, the first match refused, but we were able to locate OR for use at least twice a day was 0.4 (CI = 0.2-0.8). and interview another matched control in the sequence. For any patient, we visited 40 housing units and made three return visits before we INTRODUCTION conceded failure to secure a matched control. We were unable to obtain a control in five neighborhoods. In all, we identified and interviewed The age-adjusted incidence rate for primary tumors of the 272 controls. These 272 controls and the corresponding 272 cases were brain and cranial meninges (called BT3) in Los Angeles County included in the analysis. is about 8/100,000/year. Therefore, more than 600 BT are The Interview. A questionnaire sought information on various life diagnosed each year among Los Angeles County residents. experiences that had occurred 2 years or more prior to the year of Eighty-six % of all primary BT are gliomas or meningiomas. diagnosis of the case. The first and longest section obtained a detailed job history including information on specific job tasks and materials Studies of the etiology of brain tumors in adults have suggested used. After the work history was obtained, specific questions were asked the importance of exposure to ionizing radiation (1-5), physical about exposures, on any job, to each of: 45 substances; five processes trauma (4-7), farm residence (8-10), familial aggregation (11- (e.g., welding); radiation or radioactive materials; and farming and 12), and various occupational exposures such as vinyl chloride various related exposures. Questions were also asked about occupa monomer (13-15), rubber (16-19), formaldehyde (20-22), and tional illness or injury. There were also questions about head trauma; electric and magnetic fields (23-25). head X-rays; relatives with nervous system tumors or cancer; and This paper describes a case-control study of gliomas and consumption of tobacco, alcohol, vitamin supplements, and certain meningiomas diagnosed in men in Los Angeles County from foods. It was not feasible for interviews to be conducted blindly, but all 1980 to 1984. The purpose of this study was to investigate the questions were asked in a standard manner. Both members (case and importance of occupational exposures and of other suggested control) of each matched pair were interviewed by the same interviewer and both were interviewed by the same method, either in person or by risk factors for this disease. telephone. Interviews were conducted from August 1980 through De cember 1985. MATERIALS AND METHODS Statistical Analysis. In the analysis of dichotomous exposure vari ables, we used matched OR (the ratio of discordant pairs) to estimate Cases. The patients were black and white men with a glioma or relative risks and used the exact binomial test to calculate associated P meningioma first diagnosed during 1980-1984. Any man who was a values and CIs. Conditional logistic regression models were used for resident of Los Angeles County and 25-69 years of age at the time his the dose-response analysis of a single variable considered at more than BT was diagnosed was eligible for inclusion if he was alive and able to two levels, for tests of trend, and for multivariate analyses (27). If, for be interviewed. We decided to only include personal interviews with any variable, the information for either the patient or the control was the subjects themselves because of the level of detail we sought on job not known, we excluded the pair from the relevant analysis. All statis history and other experiences. Because we decided not to accept inter- tical significance levels (P values) cited are based on a likelihood ratio test and are two-sided for occupational factors and for tobacco and Received5/9/89; revised8/1/89; accepted8/7/89. alcohol use. P Values are one-sided for other variables which were The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in asked to test one-directional hypotheses relating to variables such as accordance with 18 U.S.C. Section 1734 solely to indicate this fact. X-rays, head trauma, and vitamin use. However, the 95% confidence ' The work was supported by Public Health Service grant POI CA 17054 from intervals (CI) shown are two-sided. In tests for trend, factors are the National Cancer Institute. 2To whom requests for reprints should be addressed. considered as continuous variables whenever possible. 3The abbreviations used are: BT. brain tumor; CI. confidence interval; OR. Analyses of occupational data compared the distributions of cases odds ratio; RR. relative risk. and controls by blue versus white collar and by major occupation (10 6137

groups) and industry groups (11 groups). Comparisons were also made to include all head injuries occurring before reference year (2 of the numbers who worked in specific occupations or industries or years before the year of diagnosis of the case) that led to loss specific groups of occupations or industries that had been identified in of consciousness, dizziness, or a medical consultation. Men the literature as having apparent excesses of brain tumors. Similarly, who had a serious head injury 20 or more years before the year comparisons were made for each of the 45 substances, five processes, of diagnosis of the case had a significantly increased risk of and other exposures queried separately as well as the hundreds of substance exposures reported during the initial job history. meningioma, but not of glioma. Head injury appeared not to be associated with glioma risk no matter what the assumed latent period (interval between first head injury and diagnosis). RESULTS The increase in meningioma risk was greater after an interval of 20 years than after intervals of 5, 10, or 30 years. In a dose- Analyses used data for 202 glioma pairs and 70 meningioma response analysis, the meningioma risk increased with an in pairs. Only a few pairs were black (11 glioma and five menin crease in the number of serious head injuries. (ORs for 0, 1, 2, gioma pairs). Glioma cases and controls were similar with and 3+ head injuries 10 or more years prior to diagnosis = 1.0, regard to median birthyear (1938 for both); mean age at date 1.6, 2.3, and 4.6; P trend = 0.01). of diagnosis of the case (45.2 years for cases; 45.1 for controls); Exposure to X-Rays. Table 3 compares cases and controls on and mean number of years of education (13.3 versus 13.7). prior dental radiography. Questions were asked about frequency Meningioma pairs were also similar with regard to these vari of any type of dental X-ray examination and frequency of full- ables: median birthyear (1924 versus 1926); mean age (55.3 mouth X-ray series in particular for two periods (up to age 25; versus 54.5); and mean years of education (13.1 for both). The after age 25). Whether or not subjects had ever been exposed distribution by histolÃ³gica! type is shown in Table 1. to dental X-rays was not a good discriminator because about Serious Head Trauma. Table 2 compares cases and controls on prior serious head injury. "Serious head injury" was defined 90% of all controls had such an exposure. Exposure to dental X-rays before age 25 was less common than exposure after age 25, and exposure to full-mouth X-ray examinations (which use Table 1 HistolÃ³gica!types of primary brain tumors (gliomas and meningiomas) in men aged 25-69, Los Angeles County, 1980-1984 an average of 18 intraoral films) was less common than expo sure to dental X-rays of any type. Few men had full-mouth HistolÃ³gica! type Number Gliomas exams before age 25. Glioma risk increased with an increase in Astrocytoma. NOS" 98 the frequency (from never to yearly) of full-mouth examinations Astrocytoma, anaplastic type 2 after age 25; a similar trend was seen for meningiomas. Both Protoplasmic, astrocytoma I Gemistocytic astrocytoma 12 glioma and meningioma risk also increased with an increase in Fibrillary astrocytoma 1 the frequency of exposure to dental X-rays of any type before Glioblastoma, NOS 43 age 25, although these trends did not reach statistical signifi Giant cell glioblastoma 1 Malignant glioma 5 cance. The way these questions were asked did not allow for an Mixed glioma 6 analysis by calendar year of exposure; the per film dose from Subependymal glioma 1 dental radiography had declined dramatically since 1920 and Choroid plexus papilloma I Ependymoma 4 as recently as the 1960s was many times higher than it is today Papillary ependymoma 1 (28). Cases and controls were similar with regard to medical Oligodendroglioma 20 Total gliomas 202 radiography of the head before reference year. Pairs in which either the case or the control had exposure to the brain or Meningiomas cranial meninges from radiation treatment to the head or neck Meningioma. NOS 16 Meningotheliomatous meningioma 33 prior to reference year (3 cases; 3 controls) were excluded from Fibrous meningioma 7 all X-ray analyses. Psammomatous meningioma 2 Occupational History. Some significant case-control differ Hemangioblaslic meningioma 6 Hemangiopericytic meningioma 1 ences related to major occupational categories. Compared to Transitional meningiomas 5 their controls, more glioma cases had spent the majority of Total meningiomas 70 a NOS. not otherwise specified. their working years in blue collar jobs [discordant pairs, 46/31; OR = 1.5; P (two-sided) = 0.09]. This difference was attribut able mainly to more cases working as transport or equipment Table 2 Comparison of male brain tumor cases (glioma and meningioma) and controls on prior serious head injury,0 Los Angeles County, 1980-1984 operatives (discordant pairs 7/3; OR = 2.3; P = 0.22) or as laborers (11/3; OR = 3.7; P = 0.05). Of those who spent the Gliomas Meningiomas majority of their working years as laborers, nine cases and no Discordant Discordant pairs OR (95% Cl) pairs OR (95% CI) controls worked as warehousemen, freight and material han Had serious head in 0.8 (0.5-1.3) (23/10) 2.3 (1.1-5.4) dlers, or stock handlers and they held such jobs for an average jury," 20 or more of 12 years. Seven of these nine said they were exposed to years before year of various types of dust (two to chlorine), three to acids, and one diagnosis41/49 each to methylethylketone, formaldehyde, petroleum products, Dose-response relationship, meningiomas plastics, and rubber. Number of serious head Number of Number of injuries* cases controls OR (95% CI) P trend Similar proportions of meningioma cases and controls spent the majority of their working years in blue versus white collar 012>330191293921g21.01.32.16.2(0.6-2.9)(0.8-5.9)(1.2-31.7)0.01 jobs, but more meningioma cases worked in service jobs for more than 5 years (discordant pairs, 10/4; OR = 2.5; P = 0.12). Five cases versus six controls worked as policemen, security " "Serious injury" was any injury that resulted in a medical visit, loss of guards, or detectives; the mean years at these jobs was 16.5 for consciousness, or dizziness. * Includes all serious injuries up to reference year (i.e., 2 years before the year cases versus 9.0 for controls. Three cases and no controls were of diagnosis of the case). professional cooks. Three cases worked an average of 17 years 6138

Table 3 Comparison of male brain tumor cases (glioma and meningioma) and controls on frequency of exposure to dental radiography, Los Angeles County, 1980-1984 Gliomas0No. Cl)Frequency Ca No. Co OR P" (95% trend*0.07trend* No. Ca No. Co OR P" (95% Cl) P

of dental X-rays up to age 25 Never or < every 5 67 84 1.0 360.2621 38 1.0 years Every 2-5 years 87 74 1.5 0.04 (1.0-2.4) 22 1.1 0.43 (0.5-2.2) (0.8-2.4)FrequencyOnce a year 40 36 1.4 0.12 (0.5-4.4)0.04 11 8 1.5 0.23

of full-mouth X-rays after age 25 Never or < every 5 168 177 1.0 510.0615 58 1.0 years Every 2-5 years 20 15 1.6 0.15 (0.7-3.6) 9 2.0 0.08 (0.8-5.0) Once(0.6-14.9)" a year 7 3 3.0 0.09 (0.2-29.5)meninges 2 1 2.5 0.23 Pairs in which either the case or control had exposure to the brain or cranial analyses.Tablefrom prior radiation treatment were excluded from these *One-sided.as

5 Other job exposures positively associated with occurrence of brain tumors janitors compared to 1 control who worked as a janitor for (gliomas and meningiomas) in men,1980-1984Gliomas+ Los Angeles County, 4 years. In addition, more meningioma cases worked as a manager or administrator for more than 5 years (17/6; OR = 2.8; P = CLExposures -/- + OR 95% 0.03). Nothing striking emerged, however, in an analysis by asked about explic itly (exposed at least specific jobs held. weekly) Employment in occupations likely to involve high exposure Rubber processing 6/1 6.0 0.7, 276.0 Used any other type of pÃas- 13/6 2.2 0.8,6.9 to electric and magnetic fields appeared to increase risk of tic?" gliomas but not meningiomas (Table 4). The association was Synthetics (nylons, rayons. 6/1 6.0 0.7,276.0 strongest with astrocytomas (OR for working in such jobs > 5 etc.)Volunteered years = 4.3; CI = 1.2-15.6). Risk increased with an increase in information on the number of years working in these occupations (P for trend exposures (ever exposed)* = 0.008). The occupations in this rubric are listed in a footnote Rubber or rubber dust 7/2 3.5 0.7, 34.5 to Table 4. Rayons InfMeningiomas+3/0 Inf 0.6. No subjects worked in the manufacture of Polyvinylchloride, but 14 glioma cases versus seven controls had jobs that involved CLExposure -/- + OR 95% contact with other plastics (i.e., other than Polyvinylchloride, asked about explic polystyrene, polyethylene, or polyurethane; discordant pairs, itly (exposed at least weekly) 13/6; Table 5). A comparison by job type showed that nine Any other petroleum prod- 18/5 3.6 1.3. 12.4 cases and one control worked in the manufacture of plastic uct such as gasoline or kerosene' products or heated plastic to melt it down, whereas similar An> other metal dusts or 13/5 2.6 0.9.9.3 numbers of cases and controls cut or shaped plastic (four cases; fumes''Volunteered four controls) or used plastic materials for bonding or covering information on (one case; two controls). Most subjects did not know the name exposures (ever exposed)* of the plastic compound they used. Rubber or rubber dust 4/0 Inf 0.9. Inf More cases than controls answered yes when asked if they Ammonia 7/2 3.5 0.7. 34.5 Kerosene10.0" 9/4 2.3 0.6. had ever worked in rubber processing (discordant pairs: glioma, Plastics other than Polyvinylchloride, polystyrene, polyethylene, and polyure 6/1; meningioma, 3/2; Table 5). In addition, when giving their thane. jobtheTable histories, more cases had volunteered previously (in * Information on frequency of exposure not available. ' Petroleum products other than paints, cooling, cutting, or lubricating oils, coal tar. soot, pitch, or smudge. 4 Comparison of male brain tumor cases (glioma and meningioma) and a Metals other than aluminum, arsenic, beryllium, cadmium, lead, mercury, controls on prior employment in occupations likely to involve high exposure to and nickel. electric1980-1984Gliomas and magnetic fields' Los Angeles County, ' Inf,infinity.occupational MeningiomasDiscordant Discordant history section of the questionnaire) that they pairsCl)14/8 OR (95% CI) pairs OR (95% were exposed to rubber or rubber dust when asked about sub 1.8 (0.7.4.8)(0.1-5.8)Dose-response 2/3 0.7 stances they came in contact with (discordant pairs: glioma, 7/ gliomasYears analysis, 2; meningioma, 4/0; Table 5). Four subjects worked in tire trend0worked No. Ca No. Co OR (95% CI) P plants: two glioma cases worked 24 and 9 years, and one years 172 182 1.0 0.05 meningioma case and one meningioma control each worked 2 >0- 5 years 16 12 1.4 (0.7,3.1) years in the manufacture of rubber tires. (0.8.4.3)">5 years 14 8 1.8 Variable recorded as binary based on subject's working more than 5 years in Six glioma cases and one control had jobs working with any jobs coded to the following 1970 U. S. Census occupation codes: 012, 171, synthetics (e.g., nylon, rayon, and other polyesters), but only 384. 430. 43 1. 475, 482. 484, 485, and 554. These jobs include electrical engineers, one of these seven (one case) worked in the manufacture of radio operators, telegraph operators, electricians, electrician apprentices, data synthetics and the other six worked only with the finished processing machine repairmen, household appliance and accessory installers and mechanics, office machine mechanics and repairmen, radio and television repair product. Three of the cases (and no controls) had volunteered men, and telephone linemen and splicers.Meningiomas"P previously that their jobs involved working with rayon, and one 6139

Downloaded from cancerres.aacrjournals.org on September 29, 2021. © 1989 American Association for Cancer Research. RISK FACTORS FOR CHOMAS AND MEN1NGIOMAS of these worked with rayon for 12 years. drinkers (i.e., drank beer at least once a month). No differences There were no remarkable differences between cases and were apparent in maximum amount of alcohol drunk regularly. controls in job exposure to specific petroleum products such as There were no significant differences between cases and con paints, lacquers, or coal tar, soot, or pitch; but more meningi- trols in their consumption of various cured meats or of citrus oma cases than controls said they had worked with other fruits. Among glioma pairs, a significant protective effect was petroleum products such as gasoline or kerosene at least weekly associated with the use of vitamin supplements, and increasing (18/5, Table 5). Ten of these cases and three controls used protection related to increasing frequency of use (one-sided P gasoline or another petroleum-based solvent to clean their for trend = 0.004). The OR for use at least twice a day was 0.4 hands or clean items they worked with, and seven cases and (95% CI = 0.24-0.77). The protective effect was somewhat four controls used it daily as a fuel and inhaled the fumes. stronger for use of vitamin C tablets than for other vitamin Three cases and three controls used airplane fuel. Ten menin- preparations. Among meningioma pairs, no protective effect of gioma cases and five controls used cooling, cutting, or lubricat vitamin supplements was seen but a protective effect was seen ing oils, and most used these daily (eight cases; four controls). for consumption of citrus fruit (OR for ate citrus five or more Seven meningioma cases and two controls had daily exposure times a week = 0.4; P = 0.07; P for trend = 0.12). Also, to inks and most mixed inks or worked with wet inks (four meningioma risk appeared to increase with increasing con cases; one control). sumption of all types of cured meats combined, but this finding Information volunteered about specific job exposures in the was not statistically significant. occupational history section of the questionnaire suggested that Fewer cases than controls had ever lived on a farm, and kerosene might be an exposure of interest (nine meningioma among the glioma pairs this difference was statistically signifi cases; four controls), but most exposures appeared relatively cant (OR = 0.5; P = 0.016). When just those subjects who lived trivial (e.g., "occasionally filled a kerosene lamp"), and only on a farm were considered, fewer cases reported exposure to two of the nine cases used kerosene at least weekly. various farm animals, crops, pesticides, and fertilizers. In an More meningioma cases had jobs that involved exposure to analysis by decade when they worked on a farm, the only metal dust and fumes (discordant pairs 13/5; Table 5). Among significant finding was that more glioma cases did farm work those with metal dust exposure, six cases and two controls in the 1950s (discordant pairs, 6/1; OR = 6.0; P = 0.05). worked as machinists and both cases and controls worked as The same number of cases and controls had blood relatives machinists for an average of 5 years. Similar numbers of cases with cancer (discordant pairs: glioma, 42/42; meningioma, 12/ and controls were exposed to metals as welders (two cases, two 12). More meningioma cases had two or more relatives with controls), inspectors (two cases, one control) or as laborers of cancer (10/3; OR = 3.3; P = 0.02), but there was nothing various sorts (four cases, two controls). remarkable about the site distribution of these cancers. A sim No other significant case-control differences were apparent ilar number of cases and controls had relatives with nervous in the analysis of occupational factors. This analysis included system tumors. Two meningioma cases had a close blood rela comparisons on the 37 specific substances and five specific jobs tive with a meningioma (one had a son diagnosed at age 17, the queried as well as comparisons by job titles, industry of em other a sister diagnosed at age 61). No cases had a prior primary ployment, and information given about exposures in the job brain or other nervous system tumor, and no controls had history section of the questionnaire. Some comparisons were nervous system tumors. made by grouping job titles or exposures in an attempt to confirm associations reported in the literature. A similar num DISCUSSION ber of cases and controls worked in the aircraft industry (glioma, 34 cases and 34 controls; meningioma, 13 cases and 14 con The present study has limited generalizability because it trols). Also, cases and controls were similar with respect to job includes only living subjects who were able to be interviewed. exposure to ionizing radiation. Although interviewers could not be blinded as to case or control Other Exposures. Table 6 compares cases and controls on status, they were blinded as to the study hypotheses, and every smoking status and consumption of alcoholic beverages. There effort was made to conduct interviews with cases and controls were no remarkable differences between cases and controls with in a like manner. regard to history of cigarette smoking when we considered age The study does support various associations reported previ started smoking, amount smoked, years smoked, and pack- ously such as the association of brain tumors with various years of exposure ( 1 pack-year is equivalent to smoking a pack occupational factors, (e.g., working in the rubber industry) and a day for a year, i.e., 7300 cigarettes). The only significant with frequent full mouth dental X-rays; however, not all such difference in relation to consumption of beer, wine, and hard previously reported differences are statistically significant here. liquor was that fewer meningioma cases than controls were beer This study does not support other previously suggested associ ations. For example, we see no increase in risk related to Table 6 Comparisons of male brain tumor cases (gliomas and meningiomas) and cigarette smoking or wine drinking. The hypothesis that expo controls by cigarette smoking and alcohol consumption, Los Angles County, sure to jV-nitroso compounds causes brain tumors has gained 1980-1984 limited support from the association with employment in the GliomasDiscor rubber industry and from the clearly protective effect seen for gliomas of frequent use of vitamin C and other vitamin supple pairsEver dant pairs(95% dant ments (both discussed below). Finally, this study, by comparing -/3532 +524453 +(0.4-1(0.5-1CI) + -/ - CI)(0.6-2.7)(0.1-0.9)data for the two major histolÃ³gica! groups of primary brain smoked tumors, has helped to clarify the relative importance of sus Ever drank at least pected risk factors such as head trauma in the etiology of each. once a month: Beer Serious Head Trauma. The possibility of recall bias must be Wine 3955- 0.71.3MeningiomasDiscor(0.5-1 .1) 1415141821 0.70.7(95%(0.3-1.4) considered in all such case-control interview studies, but it is of (0.8-1.0).2) (0.3-1.4) Hard liquor+ 44OR0.70.7 .9)177 21OR1.20.4 particular concern when investigating factors such as trauma 6140

Downloaded from cancerres.aacrjournals.org on September 29, 2021. © 1989 American Association for Cancer Research. RISK FACTORS FOR GLIOMAS AND MENING1OMAS which among lay persons is often thought to relate to tumor follow-up of the Israeli tinea capitis cohort suggests that this development. The concern is that direct questions about head association is stronger for meningiomas (RR = 9.5) than for injuries may be answered more completely by brain tumor gliomas (RR = 2.6; Ref. 32). We were unable to evaluate this patients than controls because patients may already have potential difference in our study because our data on exposure thought an injury caused their tumor; this phenomenon is called to X-rays and other sources of ionizing radiation was limited. "differential recall." For this reason, we limited our analysis of However, a test for interaction between tumor type and full this variable to "serious head injuries" (i.e., those injuries that mouth X-ray frequency after age 25 was not statistically signif resulted in a medical visit, loss of consciousness, or dizziness) icant implying no differential risk by histological type for this that occurred 2 or more years before the year of diagnosis. The X-ray variable. fact that head trauma was found to be a risk factor for menin- Occupational History. We confirmed the association of gioma but not for glioma provides further reassurance that this glioma with previous employment in the rubber industry (OR finding is not attributable to differential recall. Also, it supports = 6.0). Several earlier studies have found a similar association findings from other recent case-control studies which did not (29, 33-35) but others have not (36, 37). Four of the five find an association of head trauma with gliomas (29) but did positive studies found the association to be specific to working find an association with meningiomas (4, 5). In the present in the manufacture of tires, and the fifth study gave no infor study, the association was strongest with serious head injury 20 mation on type of job held in the rubber industry (29). The or more years prior to the year of diagnosis, and risk increased three negative studies, on the other hand, looked at employment with an increase in the number of serious head injuries. A few in other branches of the industry or in the industry as a whole. dramatic case reports suggest that trauma can lead to the In our study, two glioma cases, one meningioma case, and one development of meningioma. For example, a boiler explosion meningioma control were employed in the manufacture of tires. drove a wire 1 cm long into the brain of a man who 20 years Tire plants have been found to have high levels of contamina later was found to have a large meningioma with the wire at its tion with various /V-nitroso compounds (A'-nitrosodimethyla- center (30). Another man, who struck his head when he was mine, Â¿V-nitrosodiethylamine, /V-nitrosomorpholine, and N-ni- thrown from a stretcher by a bomb explosion, developed a small trosodiphenylamine) in the air, soil, floor scrapings, steam lump on his head at the site of the injury. Twenty years later, condensate, and compounding chemicals (38). Hot processes the lump began to gradually increase in size and after 5 years such as tire curing had the highest levels of volatile A'-nitroso was surgically removed and histologically diagnosed as a me compounds, in particular 7V-nitrosomorpholine. Various other ningioma (7). The present study further suggests that head ./V-nitroso compounds (in particular the nitrosoureas) have been trauma is an important factor in the development of meningi shown experimentally to cause brain tumors in a variety of omas, and that it is unlikely to be an important factor in the species (39, 40). development of gliomas. The association with exposure to vinyl chloride reported Exposure to X-Rays. Both major tumor types, on the other previously (14, 41) was not found in our study. The possible hand, appear to be related to the frequency of full-mouth dental association we found of gliomas with working in hot processes X-rays after age 25. There was also the suggestion of a relation using other plastics needs to be investigated in other studies. ship with the frequency of exposure to dental X-rays (of any We also confirmed an association of gliomas, in particular type) before age 25. Meningiomas have been related previously astrocytomas, with duration of employment in jobs involving to frequency of full-mouth dental X-ray series and to young age more than the usual exposure to electric and magnetic fields. at first full-mouth series (4, 5). In addition, the risk for brain This association with gliomas (23, 25) and with astrocytomas tumors of all histological types in young people age 15-24 was in particular (24) has been reported previously. Although it is increased among those who had five or more full-mouth ex tempting to assume that this increase is attributable to increased aminations starting at least 10 years before diagnosis (31). A exposure to extremely low frequency electromagnetic radiation, recent study of gliomas in adults, however, did not find an the mechanism for such an effect is not understood and the association with having ever had dental X-rays (29). This vari possible association of brain tumor risk with other exposures able (ever versus never had dental X-rays) is likely, however, to common to this industry (such as organic solvents) must be be a poor discriminator. It does not correlate well with total considered (24). exposure from dental radiography (28), and, in the present data More meningioma cases than controls reported exposure to set, about 90% of controls ever had their teeth X-rayed. A better metal dust and fumes and this difference was attributable to indicator of exposure from dental radiography is total number more cases working as machinists. Machinists and other pre or frequency of dental X-ray examinations, in particular full- cision metal workers have been shown to have an elevated brain mouth examinations. Dental X-rays account for most of the tumor risk (43). In addition, more of our meningioma cases exposure of the head from diagnostic radiography, and cumu used metal working fluids such as cooling and cutting oils. Such lative exposure from dental X-rays can be quite high (in a recent fluids have been shown to contain A'-nitroso compounds (38). study of cases and controls of similar ages to those in the Descriptive studies have shown that glioma incidence and present study, 37% had >5 rads and 4% >50 rads exposure to mortality rates are highest among those in the highest social the parotid gland, 28). classes regardless of whether social class is defined by census Since dental X-ray examinations are not particularly memo tract of residence or by occupation (43-45). The present study, rable events, recall of them may be poor. We have asked similar in contrast, found an increase in glioma risk associated with questions about dental radiography in several studies including employment (for most of one's working years) in blue collar one that validated interview information by a review of dental jobs. The most striking difference in this group was that nine charts. Results of this validation study suggest that any mis- cases and no controls had worked as warehousemen or freight classification in interview data on dental X-rays is similar for handlers. The most common exposures mentioned in relation cases and controls and that these data are good enough to use to these jobs were dusts of various sorts (seven cases) and acids alone in the analysis of case-control studies (28). (three cases). Ionizing radiation can cause brain tumors, and a recent Compared to controls, more of our meningioma cases worked 6141

Angeles county. J. Nati. Cancer Inst., 75:67-73, 1980. as managers and administrators, and more worked in the service Preston-Martin, S., Yu, M. C., Henderson, B. E., and Roberts, C. Risk industry. Similar numbers of cases and controls in service factors for meningiomas in men in Los Angeles County. J. Nati. Cancer industry jobs worked as policemen, watchmen, and firemen, but Inst., 70: 863-866, 1983. 6. Parker, H. L., and Kernohan, J. W. The relation of injury and glioma of the more cases worked as cooks or janitors. Our study did not find brain. J. Am. Med. Assoc., 97: 535-540, 1931. other previously reported associations of brain tumors with 7. Walsh, J., Gye, R., and Connelly, T. J. Meningioma: a late complication of occupational factors such as employment in the petrochemical head injury. Med. J. Australia, /.- 906-908, 1969. 8. Haenszel, W., Marcus, S. S., and Zimmerer, E. G. Cancer morbidity in urban industry or the aircraft industry. and rural Iowa. Public Service Health Monograph No. 37, U. S. Dept. Health Other Factors. We failed to confirm recently suggested as Ed. Welfare. Washington, DC: U. S. GPO, 1956. sociations of brain tumors with smoking nonfilter cigarettes 9. Choi, N. W., Schuman, L. M., and GÃ¼llen,W. H. Epidemiology of primary central nervous system neoplasms. I. Mortality from primary central nervous and with wine drinking (29), but our study had more limited system neoplasms in Minnesota. Am. J. Epidemici., 91: 238-259, 1970. data on tobacco and alcohol use and did not ask explicitly about 10. Cancer Registry of Norway: Cancer Registration in Norway. The incidence of cancer in Norway, 1953-1958. Oslo, The Norwegian Cancer Society, nonfilter cigarettes. We also found no increase in risk related 1961. to farm residence or exposure to farm animals or agricultural 11. Van der Wiel, J. J. Inheritance of glioma. Amsterdam: Elsevier, 1960. chemicals although such a relationship has been reported pre 12. Joynt, R. J., and Perret, G. E. Meningiomas in a mother and daughter. Cases without evidence of neurofibromatosis. Neurology, //: 164-165, 1961. viously (46). Cases and controls were not different in their 13. Tabershaw, I. R., and Gaffey, W. R. Mortality study of workers in the personal or family histories of previous nervous system tumors manufacture of vinyl chloride and its polymers. J. Occup. Med., 17: 509- or cancers. 518, 1974. 14. Monson, R. R., and Peters, J. M. Proportional mortality among vinylchloride The hypothesis that exposure to jY-nitroso compounds causes workers. Lancet, 2: 397-398, 1974. human brain tumors received only limited support from the 15. Waxweiler, R. J., Stringer, W., Wagoner, J. K., Jones, J., Falk, H., and Carter, C. Neoplastic risk among workers exposed to vinyl chloride. Ann. N. present study. Glioma risk was elevated among those who had Y. Acad. Sci., 271: 40-48, 1976. worked in rubber processing, an industry heavily contaminated 16. McMichael, A. J., Spirtas, R., and Kupper, L. L. An epidemiologie study of by N-nitroso compounds. Also, among glioma pairs we ob mortality within a cohort of rubber workers, 1964-72. J. Occup. Med., 16: 458-464, 1974. served a protective effect for consumption of vitamin C and 17. McMichael, A. J., Spinar, R., Gamble, J. F., and Tousey, P. M. Mortality other vitamin supplements. Vitamins C and E have been shown among rubber workers: relationship to specific jobs. J. Occup. Med., 18: to be effective in blocking the endogenous formation of N- 178-185, 1976. 18. Monson, R. R., and Fine, L. J. Cancer mortality and morbidity among rubber nitroso compounds in the gut from precursors ingested in food workers. J. Nati. Cancer Inst., 61: 1047-1053, 1978. and water (47). The protective effect was strongest among those 19. Hakama, M., and Kilpikari, I. Cancer risk among rubber workers. J. Toxicol. who took vitamins at least twice a day. It seems likely that this Environ. Health, 6: 1211-1218, 1980. 20. Harrington, J. M., and Oakes, D. Mortality study of British pathologists group took the supplements around meal time when they would 1974-1980. Br. J. Int. Med., 41: 188-191, 1984. be most effective to act as nitrosation inhibitors. Compared to 21. Walrath, J., and Fraumeni, J. F. Cancer and other causes of death among embalmers. Cancer Res., 44:4638-4641, 1984. their controls, meningioma cases did not use more vitamin 22. Stroup, N. E., Blair, A., and Erikson, G. E. Brain cancer and other causes of supplements but they did consume more citrus fruit; citrus fruit death in anatomists. J. Nati. Cancer Inst., 77: 1217-1224, 1986. contains high levels of vitamin C. Fruit consumption was also 23. Lin, R. S., Dischinger, P. C., Conde, J., and Farrell, K. P. Occupational exposure to electromagnetic fields and the occurrence of brain tumors. J. found to have a protective effect in a recent brain cancer study Occup. Med., 27: 413-419, 1985. (29); most fruits contain vitamin C and/or E. Although the 24. Thomas, L., Stewart, P. A., Stemhagen, A., Correa, P., Norman, S. A., Bleecker, M. L., and Hoover, R. N. Risk of astrocytic brain tumors associated finding of a protective effect for vitamins and fruit can be with occupational chemical exposures. A case-referent study. Scand. J. Work interpreted as being consistent with the hypothesis that brain Environ. Health, 13: 417-423, 1987. tumor risk relates to exposure to ./V-nitroso compounds there 25. Speers, M. A., Dobbins, J. G., and Miller, V. S. Occupational exposures and brain cancer mortality: a preliminary study of East Texas residents. Am. J. may be some entirely different explanation. Our study is lim Indus. Med., 13: 629-638, 1988. ited, however, in its ability to test this hypothesis. We failed to 26. Hisserich, J. C., Preston-Martin, S., and Henderson, B. E. An areawide find an association with the only other relevant factor queried: reporting network. Pubi. Health Rep., 90: 15-17, 1975. 27. Breslow, N. E., and Day, N. E. Statistical methods in cancer research. In: cured meats, which contain nitrite, a precursor of TV-nitroso W. Davis, (ed.). The Analysis of Case-Control Studies, Vol. 1, p. 211,1 ARC compounds. We have no information on other dietary sources Scientific Publication No. 32. Lyon, France: International Agency for Re of ./V-nitroso compounds, precursors, or modulators of their search on Cancer, 1980. 28. Preston-Martin, S., Thomas, D. C., White, S. C., and Cohen, D. Prior metabolism (either inhibitors or catalysts). We also have no exposure to medical and dental X-rays related to tumors of the parotid gland. data on water supply, drug use, or other potential sources of N- J. Nati. Cancer Inst., SO:943-949, 1988. 29. Burch, J. D., Craib, K. J. P., Choi, B. C. K., Miller. A. B., Risch, H. A., and nitroso exposure. Howe, G. R. An exploratory case-control study of brain tumors in adults. J. Nati. Cancer Inst., 78: 601-609, 1987. 30. Reinhardt, G. 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Susan Preston-Martin, Wendy Mack and Brian E. Henderson

Cancer Res 1989;49:6137-6143.

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