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OEM Online First, published on September 25, 2017 as 10.1136/oemed-2016-104280 Workplace

Original Article

The INTEROCC case-control study: risk of meningioma and occupational exposure to selected combustion products, dusts and other chemical agents Damien M McElvenny,1 Martie van Tongeren,1,2 Michelle C Turner,3,4,5,6 Geza Benke,7 Jordi Figuerola,3,4,5 Sarah Fleming,8 Martine Hours,9 Laurel Kincl,10 Daniel Krewski,6,11 Dave McLean,12 Marie-Élise Parent,13 Lesley Richardson,14 Brigitte Schlehofer,15 Klaus Schlaefer,15 Siegal Sadetzki,16,17 Joachim Schüz,18 Jack Siemiatycki,14 Elisabeth Cardis3,4,5 ►► Additional material is published online only. To view, please visit the journal online (http://d​ x.​doi.o​ rg/​10.​1136/​ oemed-​2016-​104280).

For numbered affiliations see end of article. Correspondence to Dr Martie van Tongeren, Centre for Occupational and Environmental Health, Centre for Epidemiology, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Oxford Road, Manchester, M13 9PL, UK; ​ martie.j​ .​van-t​ ongeren@​ manchester.​ac.​uk Received 30 December 2016 Revised 8 June 2017 Accepted 20 June 2017

Abstract Background Little is known about occupational risk factors for meningioma. Objectives To study whether risk of meningioma is associated with several occupational exposures, including selected combustion products, dusts and other chemical agents. Methods The INTEROCC study was an international case-control study of brain cancer conducted in seven countries. Data collection by interview included lifetime occupational histories. A job exposure matrix was used to derive estimates of exposure for the 12 agents. ORs for ever versus never exposed and for exposure-response using duration of exposure and cumulative exposure were derived using conditional logistic regression stratified by sex, age group, country/region, adjusted for education. Results These analyses included 1906 cases and 5565 controls. For 11 of the 12 agents, no excess risk was found for ever exposed. For ever exposure to oil mists, an elevated OR of 1.57 (95% CI 1.10 to 2.22, 51 exposed cases) was found. Statistically significant exposureresponse relationships were observed with cumulative exposure (p=0.01) and duration of exposure (p=0.04). Among women, there were also significant trends for cumulative and duration of exposure to asbestos and excesses in the highest exposure categories for formaldehyde. Conclusions  Most agents examined did not provoke excess risks of meningioma. The main finding from this study is that it is the first study to identify a statistical association between exposure to oil mists and meningioma. This may be a chance finding or could be due to confounding with iron exposure and further research is required to understand whether the relationship is causal.

Introduction

To cite: McElvenny DM, van Tongeren M, Turner MC, et al. Occup Environ Med Published Online First: [please include Day Month Year]. doi:10.1136/ oemed-2016-104280

Meningioma is a type of brain tumour, usually benign, arising from the meningeal tissue of the brain, with often serious and potentially fatal consequences.1 In the USA, meningioma accounts for a third of all primary brain and central nervous system tumours and the age-adjusted incidence rate is about 7 per 100 000 person-years.1 The incidence

What this paper adds ►► Little is known about occupational risk factors

for meningioma.

►► The INTEROCC study is the largest case-

control study of meningioma and occupational risk factors, with data collected from seven countries. ►► Occupational exposure to mineral oil appeared to be associated with elevated risk of meningioma. ►► Among women, there was also some indication of exposure-response for asbestos and some indication of excess risks from formaldehyde in the highest exposure categories. ►► No association was observed with other occupational substances investigated in this paper, which included combustion products, mineral and organic dusts and other chemical agents. is rising in some countries, but remains stable in others.2 Differences in cancer registration practices between countries mean that incidence rates differ considerably between countries. Meningiomas exhibit a range of morphological appearances, with WHO suggesting there are up to 15 histopathological variants.2 Five-year survival has been reported as 55% and 3-year survival at over 85%.2 The incidence rate increases rapidly with age and is twice as high in females as in males.2 The only established environmental risk factor for meningioma is exposure to ionising radiation, with some doubt as to the dose required to trigger excess risk.1 Results from other epidemiological studies are somewhat sporadic. Results from the German component of the INTEROCC study did not find an increased risk of meningioma for occupations in the agricultural, construction, transport, chemical, electrical/electronic or metal industries.3 In a different international case-control study, an increased risk of meningioma was found in cooks.4 One US case-control study found elevated risks of meningioma for auto body painters, designers and decorators, military occupations, industrial

McElvenny DM, et al. Occup Environ Med 2017;0:1–11. doi:10.1136/oemed-2016-104280

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Workplace production supervisors, teachers and managers.5 Additional analyses found inconsistent evidence for an association between the use of synthetic hair dye and meningioma6 and an association between meningioma and herbicide or insecticide exposure among women, but not in men.7 A French population-based case-control study concluded that meningioma may be caused by occupational or residential exposure to electromagnetic fields,8 although the evidence in support of an association with occupational exposure from the INTEROCC international study was somewhat weaker.9 No association was found between mobile phone use and meningioma.10 11 A Chinese case-control study found significant associations for occupational exposure to some metals such as lead, tin and cadmium.12 We previously published results investigating link between meningioma and occupational exposures for a number of families of organic solvents (aliphatic hydrocarbons, alicyclic hydrocarbons, aromatic hydrocarbons, chlorinated hydrocarbons and other organic solvents) or specific solvents (benzene, gasoline, methylene chloride, perchloroethylene, trichloroethylene, 1,1,1-trichloroethylene and toluene), which failed to show significant associations between meningioma and any of the solvents.13 The analyses of a number of metals failed to show significant associations, apart from a positive borderline significant association for iron exposure in women.14 Because these tumours occur more often in women than in men1 and supported by some findings of an association between meningioma and hormone replacement therapy,15 16 it has been suggested that hormones play a role in the aetiology of meningioma. Use of oral contraception does not appear to influence the risk.1 Asthma, hay fever and eczema are thought to be protective in relation to meningioma risk.17 Based on the INTEROCC study, the largest case-control study on occupational risk factors for brain tumours, the present paper examines associations between the risk of developing meningioma and occupational exposures to 12 agents, commonly present in the occupational environments and for which there is some evidence that they may cause damage to the brain18: combustion fumes (diesel engine exhaust, gasoline engine exhaust, bitumen fumes, benzo(a)pyrene and polycyclic aromatic hydrocarbons), mineral and organic dusts (asbestos, quartz, animal dusts, wood dust) and some other agents (formaldehyde, oil mist and sulphur dioxide).

Methods Study population

INTEROCC is a seven-country population-based case-control study formed from the parent INTERPHONE study.19 Incident cases of primary meningioma were recruited from 11 study centres in Australia, Canada, France, Germany, Israel, New Zealand and the UK from the year 2000 to 2004 using a common protocol. The age range of study subjects was defined as follows: in Germany, 30–69 years; in the UK, 18–69 years; in Israel, over 18 years; in all other countries, 30–59 years. Eligibility of cases was confirmed either histologically, or in approximately 25% of cases, through unequivocal diagnostic imaging. Population control recruitment varied by country, but all controls were selected from population registers and were either frequency matched or individually matched to cases in each study centre by sex and year of birth (5-year categories). To maximise statistical power, we used all eligible controls from the INTEROCC study, including those collected for the glioma cases. The reference date for controls was calculated as the interview date minus the median difference between case diagnosis and interview date for each study country. Written informed consent 2

was obtained from all study participants prior to the in-person interview. The study questionnaire solicited demographic, medical and lifetime occupational histories. In a small proportion of cases (5%), proxy interviews were conducted where the case participant had died or could not be interviewed. Ethics approval from all appropriate national and regional research ethics boards was obtained including the Ethical Review Board of the International Agency for Research on Cancer (IARC) for INTERPHONE and the Municipal Institute for Medical Investigation (IMIM) Barcelona for INTEROCC.

Occupational exposure assessment

The exposure assessment methodology is described in more detail elsewhere.20 Briefly, each job within the occupational histories was coded using International Standard Classification of Occupations 1968 (ISCO68)21 by a trained occupational hygienist. The coding consistency between countries was tested before and after a comparison exercise using a small subset of the job titles with any discrepancies discussed among the coders. This exercise resulted in a moderate improvement in coding consistency.13 A job exposure matrix was developed based on the Finnish Job Exposure Matrix (FINJEM),22 which assigns estimates of the proportion of workers in the given occupation who are considered exposed to the given agent and mean exposure levels of each agent for those who are considered exposed. Exposure estimates (probability and level of exposure) were obtained from the modified job exposure matrix (INTEROCC JEM) by: i) developing a cross-walk between the Finnish occupational classification used in FINJEM to ISCO68; ii) splitting the early component of the entire 1945–2003 time period (1960–1984) into two different time periods (1960–1973 and 1974–1984) to enable exposures to change over this time period; iii) updating exposure estimates based on a comparison with data from a study of occupational lung cancer risk in Montreal, Canada23 and iv) peer-reviewing the final updated estimates for generalisability to each of the seven study countries by local occupational hygienists.20 For example, the internal calibration of the ISCO68 codes linked to ‘Machine and engine mechanics’ resulted in relatively high exposures to aromatic hydrocarbons for the ISCO68 code ‘Office machine mechanic’, which were in the same order of magnitude as mechanics of heavy and transport machinery. It was decided that this was not realistic and exposure to aromatic hydrocarbons was reduced for this occupational group. Each job in each subject’s job history was linked to the INTEROCC JEM to infer possible occupational exposures. The 12 agents under consideration in this paper were subsequently evaluated for possible exposure in each job. Exposure to each agent was defined as having had an occupation for at least 1 year where the estimated probability of exposure (P) was 25% or more. Risk analyses were conducted as a function of categorical indicators of ever/never exposed, quartiles of cumulative exposure (calculated as the sum over all jobs of the product of duration of job and concentration). Duration of exposure categories were chosen and use the same categorisation for consistency, as other INTEROCC study analyses.

Statistical analysis

Adjusted ORs and 95% CIs for associations between potential carcinogens of interest and meningioma were estimated using conditional logistic regression stratified by sex, 5-year age groups, country-region and adjusted for education in all seven countries combined. Three exposure indices, decided on a priori, were used: (1) ever/never exposed; (2) lifetime

McElvenny DM, et al. Occup Environ Med 2017;0:1–11. doi:10.1136/oemed-2016-104280

Downloaded from http://oem.bmj.com/ on September 30, 2017 - Published by group.bmj.com

Workplace Table 1  Description of selected characteristics of the study population  Cases

 Controls

Characteristic

N

%

N

%

Total

1906

100

5565

100

 Males

507

26.6

2484

44.6

 Females

1399

73.4

3081

55.4

Sex

Age (years)  

The INTEROCC case-control study: risk of meningioma and occupational exposure to selected combustion products, dusts and other chemical agents.

Little is known about occupational risk factors for meningioma...
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