Occupation and Adult Gliomas

Susan E. Carozza1, Margaret Wrensch2, Rei Miike2, Beth Newman3, Andrew F. Olshan4, David A. Savitz4, Michael Yost5 and Marion Lee2

1 Department of Epidemiology and Biostatistics, School of Rural Public Health, Texas A&M University System Health Science Center, College Station, TX.
2 Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, CA.
3 School of Public Health, Queensland University of Technology, Queensland, Australia.
4 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC.
5 Department of Environmental Health, University of Washington, Seattle, WA.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Lifetime job histories from a population-based, case-control study of gliomas diagnosed among adults in the San Francisco Bay area between August 1991 and April 1994 were evaluated to assess occupational risk factors. Occupational data for 476 cases and 462 controls were analyzed, with adjustment for age, gender, education, and race. Imprecise increased risks were observed for physicians and surgeons (odds ratio (OR) = 3.5, 95% confidence interval (CI): 0.7, 17.6), artists (OR = 1.9, 95% CI: 0.5, 6.5), foundry and smelter workers (OR = 2.6, 95% CI: 0.5, 13.1), petroleum and gas workers (OR = 4.9, 95% CI: 0.6, 42.2), and painters (OR = 1.6, 95% CI: 0.5, 4.9). Legal and social service workers, shippers, janitors, motor vehicle operators, and aircraft operators had increased odds ratios only with longer duration of employment. Physicians and surgeons, foundry and smelter workers, petroleum and gas workers, and painters showed increased risk for both astrocytic and nonastrocytic tumors. Artists and firemen had increased risk for astrocytic tumors only, while messengers, textile workers, aircraft operators, and vehicle manufacturing workers showed increased risk only for nonastrocytic tumors. Despite study limitations, including small numbers for many of the occupational groups, a high percentage of proxy respondents among cases, and lack of specific exposure information, associations were observed for several occupations previously reported to be at higher risk for brain tumors generally and gliomas specifically. Am J Epidemiol 2000;152:838–46.

brain neoplasms; glioma; nervous system diseases; occupations

Abbreviations: CI, confidence interval; OR, odds ratio.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Gliomas are the most common form of primary malignant brain tumor in adults (1Go, 2Go). Despite aggressive treatment with surgery, radiation, and chemotherapy, these tumors are most often rapidly fatal. The 5-year survival rate is only 30.2 percent (3Go). Among those patients who do survive over 5 years, many are left with permanent disabilities (4Go). Although the etiology of brain tumors in adults remains largely unknown, epidemiologic studies have suggested that occupational exposures may be involved in the development of these cancers. Studies spanning the past few decades have found increased risk of brain tumors among workers in particular industries, including synthetic rubber manufacturing (5GoGoGoGo–9Go), polyvinyl chloride production (10GoGoGoGoGoGo–16Go), petrochemical refineries (17GoGoGoGoGo–22Go), and chemical plants (22GoGoGo–25Go). Specific occupations that have been reported to show an association with brain tumors include farmers and agricultural workers (23Go, 26GoGoGoGo–30Go), electrical workers (9Go, 31GoGoGoGoGoGoGoGoGo–40Go), and machinists and metalworkers (19Go, 24Go, 30Go, 41Go). Several studies have noted increased risk among "white-collar" occupations, jobs generally thought to have minimal occupational exposure to hazardous chemical or physical agents as compared with "blue-collar" jobs. Health care workers (medical professionals, dentists, pharmacists, and veterinarians) (22Go), writers, artists, and entertainers (41Go), and teachers (28Go, 41Go) are all white-collar occupations that have shown increased risk for brain tumors.

To date, the majority of epidemiologic studies investigating possible occupational risks for these tumors have not had access to lifetime job histories for study subjects but, rather, have had to rely on "usual" or "last" occupation as reported on death certificates (5Go, 21Go, 29Go, 31GoGoGo–34Go), company records (6Go, 7Go, 10GoGoGoGoGoGoGoGo–18Go, 20Go), or cancer registry data (27Go, 30Go, 37Go, 38Go). In addition, studies generally have grouped all tumor types together and so have been unable to assess occupational risk for histologically similar types of malignant gliomas, subgroups that probably have distinct etiologic pathways (42Go, 43Go). The goal of this study was to fully utilize both lifetime job history and detailed pathology data to address associations between occupation and malignant gliomas.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Study participants
Cases eligible for inclusion were all histologically confirmed, incident cases of glioma (International Classification of Diseases for Oncology, second edition (ICD-O-2), morphology codes 9380–9481) in adults aged 20 years and older diagnosed in six San Francisco Bay area counties (Alameda, Contra Costa, Marin, San Mateo, San Francisco, and Santa Clara) between August 1991 and April 1994. The Northern California Cancer Center identified 603 eligible cases and interviews were completed for 492 (82 percent). Twelve percent of eligible cases declined to participate, physicians refused contact with 2 percent, and we were unable to locate or contact 25 cases or a suitable proxy (4 percent). Sixteen cases were subsequently excluded because neuropathology review indicated that the subject did not have either glioma or medulloblastoma (n = 4), permission for review was not obtained (n = 4), tumor specimens were not available (n = 3), or tumor specimens were insufficient for diagnosis (n = 5). On average, cases were interviewed within 4 months and proxies within 8 months of cases' diagnoses. Almost half of the job history data for cases (45.6 percent) was provided by a proxy respondent, as compared with 0.9 percent among controls. The proportion of proxy respondents among cases increased with age, reaching a high of 77.0 percent of the total cases aged 65 years and older. Spouses and adult children were the most common type of proxy respondents, accounting for 80 percent of all proxies.

Controls were frequency matched by 5-year age groups, gender, and race/ethnicity and identified by random-digit dialing using methods described by Waksberg (44Go) and refined by Harlow and Davis (45Go). A total of 754 apparently eligible controls were obtained through random-digit dialing of 6,612 phone numbers. Of the 5,858 numbers that did not yield eligible controls, 49 percent were either businesses (n = 1,024), fax machines or modems (n = 347), or not working (n = 1,495); 9 percent (n = 547) gave no response after 10 tries; 26 percent (n = 1,502) were enumerated but had no eligible household member; 5 percent (n = 283) refused information; 0.6 percent (n = 37) were eligible but too ill; 4 percent (n = 231) were not English speaking; and 7 percent (n = 392) were eligible but the quota for their age/gender/ethnic group had already been filled. Of the 754 apparently eligible controls, two indicated that they were related to cases, 11 lived out of the area, and nine did not have sufficient English for interview. Interviews were completed with 63 percent (462/732) of eligibles, 32 percent declined to participate, and 5 percent could not be reached for interview.

Exposure classification
Exposure information was collected from cases and controls through a standardized questionnaire administered by trained interviewers in the subjects' homes or an alternate location of their choosing. A detailed lifetime job history was collected for each study participant. For each job reported, subjects also supplied information on the industry, name and location of the company/agency, a description of the daily work activities, starting date, duration of job, and hours worked per week.

Descriptions of job title and industry were initially coded by one person (S. E. C.) using the 1980 Standard Occupational Classification and 1987 Standard Industrial Classification schemes. Coding was done without knowledge of case or control status. After assignment of all occupation and industry codes, the data were sorted by code and manually reviewed for consistency. For this report, jobs were then more broadly classified into 56 occupational categories in order to aggregate jobs into a manageable number of groups with presumably similar job tasks and potential exposures within occupational categories (46Go). Categories are generally based on occupation, as that was the primary factor determined by an industrial hygienist to influence exposure (e.g., dentist, painter). For some occupations, however, industry was determined to be more critical to determining exposure (e.g., laborers), and those jobs are grouped into categories of industry. Of the 5,959 individual jobs reported by the study subjects, only 76 did not fit clearly into any of the predetermined occupational categories and were not included in the analyses. Duration of job was calculated for every job held at least 6 months during a subject's lifetime, based on beginning and ending dates of employment. This was calculated for all employment and with the most recent 10 years excluded to allow for a hypothesized 10-year latency period between exposure and clinical recognition of disease. Duration data were consolidated when multiple instances of jobs within the same occupational grouping occurred in a study subject.

Statistical methods
Multiple logistic regression was used to calculate maximum likelihood estimates of odds ratios and corresponding 95 percent confidence intervals for each occupational group with three or more exposed cases. Odds ratios were estimated for "ever" employed, employed less than 10 years, and employed for 10 years or more, both with and without the assumption of a 10-year latency period. Subjects not employed in the occupational category being evaluated served as the "nonexposed" referent category. To evaluate differences in risk among differing histologic subgroups of gliomas, odds ratios were calculated for astrocytic tumors only (i.e., glioblastoma multiforme and astrocytoma) and "other" tumors as a group. Based on previous reports, risk factors controlled for in the analyses included age (20–54 years, >=55 years), gender, years of education (<16 years, >=16 years), and race (White, non-White). The statistical modeling was done using SAS software (47Go). Discussion of the results focuses on odds ratios of 1.5 or greater or 0.7 or less.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Job title analysis
The distributions of selected risk factors among cases and controls and corresponding crude odds ratios are presented in table 1. Overall, a mean of 6.3 jobs was reported per subject. Among cases, the mean number of jobs reported was 5.6, compared with 7.1 among controls. Cases represented by proxies had fewer jobs reported when compared with directly interviewed cases (4.7 vs. 6.3). A substantial number of the individual jobs reported for each subject were multiple instances of similar occupations that could be consolidated within a single occupational category. Once consolidated, the average number of occupational categories reported for study subjects was 3.3; among controls, the average was 3.6, among directly interviewed cases, 3.3, and among proxy respondents, 2.8.


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TABLE 1. Selected characteristics of malignant glioma cases and controls, San Francisco Bay Area Adult Glioma Study, 1991–1995

 
The distribution of occupations among cases and controls is presented in table 2, and results of the analyses of associations between occupational groups and gliomas are presented in table 3. The occupational categories with the largest number of subjects included salesmen, clerks, managers and administrators, food service workers, teachers and librarians, farm managers and workers, and armed forces. The number of subjects in the remaining occupational categories was often quite small, resulting in very wide confidence intervals for many of the risk estimates.


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TABLE 2. Distribution of occupational groupings among cases and controls, San Francisco Bay Area Adult Glioma Study, 1991–1995

 

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TABLE 3. Associations between malignant gliomas and occupation, San Francisco Bay Area Adult Glioma Study, 1991–1995

 
Among health care professions, physicians and surgeons showed elevated odds ratios (odds ratio (OR) = 3.5, 95 percent confidence interval (CI): 0.7, 17.6). The risk for this group increased when a latency period was considered, and there was some indication of increasing risk with increasing duration. Examination of the specific job activities reported revealed no particular medical specialty in the category of physicians and surgeons.

Among other occupations traditionally considered white-collar, legal and social service workers had elevated odds ratios only when exposure was defined as employment duration of 10 years or more. Artists also showed an irregular pattern of elevated risk.

Several white-collar occupational categories displayed lowered odds ratios both with and without a latency period, including engineering and science technicians, entertainers and athletes, photographers and photo processors, and clerks.

As with the above white-collar categories, the majority of blue-collar occupations did not exhibit increased risk, either for all time periods or when allowing for a latency period. Shippers, however, had a greater than twofold risk associated with long-term employment when a latency period was considered. Foundry and smelter workers had an odds ratio of 2.6 (95 percent CI: 0.5, 13.1) for ever employed. The petroleum and gas workers' group had an odds ratio of 4.9 (95 percent CI: 0.6, 42.2) both with and without a latency period. Painters had elevated odd ratios of twofold and greater among those employed less than 10 years, regardless of latency. Janitors, motor vehicle operators, and aircraft operators all had approximately twofold or higher risk associated with long-term employment. The odds ratio for ever employed among firemen was 2.7 (95 percent CI: 0.3, 26.1); however, this measure was based on only three cases.

Among blue-collar workers, lowered odds ratios were seen among personal service workers, farm managers and workers, sawmill workers, welders and cutters, electricians, electrical and electronics workers, carpenters and wood workers, service station attendants, vehicle mechanics, and mechanics (not elsewhere classified). Printers had consistently lower odds ratios only when allowing for a latency period.

Histologic subgroups
The majority of gliomas diagnosed in the study population were astrocytic (77 percent), and 76 percent of the astrocytic tumors were glioblastomas. More males than females were diagnosed with astrocytic tumors (56.1 percent vs. 43.9 percent). Among astrocytomas, approximately 66 percent were diagnosed among subjects less than 55 years of age, in contrast to only 31 percent of glioblastomas. The histologic types comprising "other" tumors consisted of mixed glioma, oligodendroglioma, medulloblastoma, ependymoma, glioma not otherwise specified, juvenile pilocytic astrocytoma, and ganglioglioma. The majority of these tumors were diagnosed in males (61 percent) and in subjects less than 55 years of age (83 percent).

Table 4 presents the estimated odds ratios for the association of each occupational group with astrocytic and other tumors. As with the previous analyses, many of the occupational groups had small numbers of subjects when stratified by tumor type, as reflected in the wide confidence intervals. Physicians and surgeons, foundry and smelter workers, petroleum and gas workers, and painters showed an elevation in risk for both tumor groupings. Artists and firemen had increased odds ratios for astrocytic tumors only, while messengers, textile workers, aircraft operators, and vehicle manufacturing showed increased risk only for nonastrocytic tumors. Occupational groups with substantially lowered odds ratios in the earlier analyses continued to have odds ratios below 1.0 when tumor type was evaluated.


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TABLE 4. Associations between histologic subgroups of malignant gliomas and occupation, San Francisco Bay Area Adult Glioma Study, 1991–1995

 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The majority of occupational categories examined showed no association with adult gliomas, regardless of length of employment or consideration of a 10-year latency period. Of the few occupations that did show evidence of increased odds ratios, however, several have been reported to be at higher risk in previous studies. Associations with medical professionals in general and with physicians, dentists, and dental technicians in particular have been reported in several studies (21Go, 22Go, 41Go). It has been suggested that this increase is due in part to increased access to medical care among health professionals, resulting in greater diagnostic sensitivity among these occupations. With the widespread availability and increased utilization of computerized axial tomography and nuclear magnetic resonance imaging technology in more recent years, however, it seems unlikely that such a bias would exist to the extent of substantially influencing more current data. Professionals in a medical setting do have potential occupational exposures including numerous biologic agents and chemicals such as disinfectants, antiseptics, and pharmaceutical preparations as well as radiation (41Go).

Although based on small numbers (five cases, one control), one of the strongest associations seen in this study was with petroleum and gas workers. Examination of the job activities reported among petroleum and gas workers in our study revealed that workers in this group included oil field roustabouts as well as refinery workers, indicating that the risk may not be confined to the refinery setting. Although there have been several reports of increased risk in this occupation/industry group (12Go, 20Go, 21Go, 48Go), the risk associated with specific exposures remains to be determined.

We found a greater than twofold increased risk for painters employed less than 10 years, regardless of latency. This is similar to risk estimates of 1.5 and greater that have been reported previously for painters (21Go, 24Go). Whereas we found an elevated risk for astrocytic tumors (OR = 1.8, 95 percent CI: 0.5, 5.8), the only other study to report risk by tumor type found no elevation in risk for astrocytic tumors (21Go). Painters historically have been exposed to solvents through use of oil-based paints; however, the introduction of latex paints has substantially reduced the amount of solvents in commercially used paints. Painters also are exposed to solvents in the solutions used for cleaning of surfaces and paint applicators. Heineman et al. (49Go) found a statistically significant twofold increased risk for astrocytic tumors among occupations with a high probability of exposure to methylene chloride, such as painters. These are exposures shared to some extent by artists, another occupational group for which we had some indication of increased risk. All but one of the artists in our study were painters working in a variety of mediums (e.g., oil paints, water color, pen and ink).

Legal and social service workers have not been specifically grouped as such in previous studies. However, Demers et al. (21Go) did not find an excess relative risk for social, legal, recreation, and religious workers. The risk seen in our study in this occupational category was most pronounced with longer employment. Although speculative, the lack of common chemical or physical agents in this group does open the possibility of an infectious etiology. Legal and social service workers are occupations that entail a great deal of contact with diverse people in a variety of settings, giving ample opportunity for exposure to any number of infectious agents. There have been several reports of the isolation of viruses or virus-like particles in human cerebral tumors or tumor cell lines; however, the etiologic role of these agents is unclear (50Go).

There are several limitations to this study that are largely inherent to the approach. Although the numbers for occupational groups were often small, resulting in imprecise estimates, we attempted to gain validity in return for the loss of precision by grouping jobs with similar exposures together. Job titles can serve only as a surrogate for specific job-related exposures, however, and despite efforts to group jobs into categories with similar occupational exposures, the types of jobs classified together are still quite likely to be heterogeneous in terms of specific exposures. Given the imprecision of the observed risk estimates, conclusions as to the relative importance of the findings presented were based on the consistency of the risk pattern and, to some extent, results of previous studies.

Another study limitation was the high percentage of proxy respondents for cases. This is an unfortunate, but unavoidable, limitation when investigating the etiology of malignant gliomas. As has been noted in various studies, it is difficult to assess the impact on risk estimates of data derived from proxies (51Go, 52Go). Proxies tend to underreport the number of lifetime jobs, particularly short-term jobs and jobs held furthest from the time of outcome (53Go, 54Go). This is consistent with our finding of a lower mean number of jobs reported among cases with proxy respondents as compared with directly interviewed cases. If jobs held in the distant past were not reported by the cases' proxy respondents and these jobs were etiologically relevant, then risk estimates could be attenuated. If the fewer number of jobs reported by proxies was due, however, to underreporting of changes in employer or minor variations in job titles, while recall of general occupation was accurate, then the effect on risk estimates should be minimal.

This study differs from the majority of previous studies on the association of brain tumors and occupational exposures in several ways, including: 1) the limitation of tumors to adult gliomas; 2) the availability of lifetime job history data that allowed for crude evaluation of latency and dose-response; and 3) the use of an occupational classification system that incorporates job title and industry together into distinct categories with presumably similar exposures. Despite these differences in study design and the noted limitations, many of the findings reported here support observations from earlier studies, highlighting the need for future studies of occupation and gliomas to focus on risk associated with specific exposures within these higher risk job and industry groups.


    ACKNOWLEDGMENTS
 
This work was supported by grant RO1CA52689 from the National Institutes of Health.

Thanks are extended to Drs. Richard Davis and Kenneth Aldape for neuropathology review. The authors also appreciate the invaluable contributions of Jennifer Touchstone, Luana Acton, Christine Choy, Martha Duncan, Amanda Ettinger, Jennifer Guilfoyle, Kenneth Law, Betty Chang Lee, Csaba Polony, M. Moore Robinson, Pascal Sisich, Marisa Suzuki, and Karla Vasconcellos for research assistance.


    NOTES
 
Reprint requests to Dr. Susan E. Carozza, TAMU Health Science Center, School of Rural Public Health, 260 Centeq Bldg., College Station, TX 77843-1266 (e-mail: scarozza{at}medicine.tamu.edu).


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 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
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Received for publication May 27, 1999. Accepted for publication February 4, 2000.