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Laryngeal and Hypopharyngeal Cancers and Occupational Exposure to Formaldehyde and Various Dusts: a Case-Control Study in France

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Laryngeal and Hypopharyngeal Cancers and Occupational Exposure to Formaldehyde and Various Dusts: a Case-Control Study in France Occup Environ Med 2000;57:767–773 767 Occup Environ Med: first published as 10.1136/oem.57.11.767 on 1 November 2000. Downloaded from Laryngeal and hypopharyngeal cancers and occupational exposure to formaldehyde and various dusts: a case-control study in France Laurent Laforest, Danièle Luce, Paquerette Goldberg, Denis Bégin, Michel Gérin, Paul A Demers, Jacques Brugère, Annette Leclerc Abstract The highest age adjusted incidences of laryn- Objectives—A case-control study was geal and hypopharyngeal cancers in Europe are conducted in France to assess possible found in France.1 associations between occupational expo- Numerous epidemiological studies have sures and squamous cell carcinomas of sought to identify aetiological factors for these the larynx and hypopharynx. cancers. Smoking and alcohol consumption are 23 Methods—The study was restricted to well established as major risk factors. Smok- men, and included 201 hypopharyngeal ing and drinking combined seem to have a 45 cancers, 296 laryngeal cancers, and 296 multiplicative eVect. Several studies suggest that some dietary constituents could influence controls (patients with other tumour 6 sites). Detailed information on smoking, laryngeal and pharyngeal tumours. alcohol consumption, and lifetime occu- Studies have also assessed some of the occu- pational history was collected. Occupa- pational exposures that might increase the risk of these cancers. The indicators of occupa- tional exposure to seven substances tional exposure most often used have been job (formaldehyde, leather dust, wood dust, titles or industrial sectors. Increased risks have flour dust, coal dust, silica dust, and been reported for several occupational groups, textile dust) was assessed with a job expo- including textile workers,7–9 metal processors,10 sure matrix. Exposure variables used in coal miners,7 mechanics,11 12 and machinists.13 the analysis were probability, duration, Although the association between exposure to and cumulative level of exposure. Odds asbestos and laryngeal cancer has been repeat- ratios (ORs) with their 95% confidence edly found, the existence of a causal relation is intervals (95% CIs) were estimated by still debated.14–19 Occupational exposure to unconditional logistic regression, and polycyclic aromatic hydrocarbons20 has also were adjusted for major confounding fac- been suspected. Several studies have found an tors (age, smoking, alcohol, and when rel- increased risk of laryngeal cancer among work- evant other occupational exposures). ers exposed to sulphuric acid.21–23 No definitive Results—Hypopharyngeal cancer was conclusions can be drawn about the association found to be associated with exposure to between laryngeal or hypopharyngeal cancer http://oem.bmj.com/ Institut National de la coal dust (OR 2.31, 95% CI 1.21 to 4.40), and occupational exposures to wood dust or Santé et de la with a significant rise in risk with prob- formaldehyde.24 Most epidemiological exami- Recherche Médicale, ability (p<0.005 for trend) and level nations of occupational factors have, overall, Unité 88, (p<0.007 for trend) of exposure. Exposure yielded results that are either non-significant or Saint-Maurice, 14 rue du Val d’Osne, 94415 to coal dust was also associated with an require further investigation for confirmation. Saint-Maurice Cedex, increased risk of laryngeal cancer (OR A case-control study in France examined France 1.67, 95% CI 0.92 to 3.02), but no dose- occupational risk factors for laryngeal and L Laforest response pattern was found. A significant hypopharyngeal cancers. Previous reports from on October 2, 2021 by guest. Protected copyright. D Luce relation, limited to hypopharyngeal can- this study have analysed associations with job P Goldberg 25 A Leclerc cer, was found with the probability of titles and industrial sectors, and with asbestos exposure to formaldehyde (p<0.005 for and man made vitreous mineral fibres.26 The Université de trend), with a fourfold risk for the highest present paper deals with the possible associ- Montréal, Québec, category (OR 3.78 , 95% CI 1.50 to 9.49). ation between these two cancer sites and expo- Canada When subjects exposed to formaldehyde sure to formaldehyde, leather dust, wood dust, D Bégin textile dust, flour dust, coal dust, and silica M Gérin with a low probability were excluded, the risk also increased with duration (p<0.04) dust. University of British and cumulative level of exposure (p<0.14). Columbia, Vancouver, No significant association was found for Canada any other substance. Material and methods P A Demers Conclusion—These results indicate that STUDY POPULATION Cases were male patients with incident primary exposure to formaldehyde and coal dust Institut Curie, Paris, laryngeal and hypopharyngeal squamous cell France may increase the risk of hypopharyngeal J Brugère cancers, diagnosed and histologically con- cancer. firmed in 15 French hospitals between 1 Janu- (Occup Environ Med 2000;57:767–773) Correspondence to: ary 1989 and 30 April 1991. Because of the Dr Danièle Luce paucity of other histological types (less than [email protected] Keywords: laryngeal cancer; hypopharyngeal cancer; occupational exposure; job exposure matrix; formalde- 1%), only squamous cell cancers were consid- Accepted 6 July 2000 hyde; coal dust ered, and because of the low incidence of www.occenvmed.com 768 Laforest, Luce, Goldberg, et al Occup Environ Med: first published as 10.1136/oem.57.11.767 on 1 November 2000. Downloaded from hypopharyngeal and laryngeal tumours among for a study on sinonasal cancer29 (the JEM is women, only men were recruited. The study available from the authors). initially identified 664 patients meeting these For each ISCO-ISIC combination and for criteria. Of these, 136 (20.5%) could not be each substance, the JEM gives the probability interviewed because of health problems of exposure, and the level of exposure in (n=40), death before an interview could be categories. The cut oV points used for the cat- conducted (n=11), refusal to participate egories of level and probability, according to (n=22), or because they could not be located the substance, are presented in table 1. When (n=63). In all, the study finally included 206 the probability of exposure was less than 10% men with hypopharyngeal cancer, 315 with (for wood dust and leather dust) or less than laryngeal cancer, and seven with cancers of 1% (for the other substances), the job was con- both the larynx and hypopharynx. Controls sidered to be unexposed. were patients with primary cancers of diVerent For a given substance, for each job i of each sites, selected by frequency matching on age subject, the JEM provides the probability of and recruited between 1987 and 1991 in the exposure Pi and the level of exposure Li. The same hospitals as the cases or in similar hospi- job duration Di was also available. Subjects tals nearby. The aim was to obtain a control could have had several successive jobs i group of the same size as the group of cases of exposed to the same substance throughout laryngeal cancer. Of the 355 controls identi- their working life. Several exposure variables fied, 50 (14%) could not be interviewed, were calculated to summarise the subject’s life- because of medical conditions (n=14), refusal time exposure: maximum probability of (n=14), or because they could not be located exposure=max (Pi); total duration of exposure (n=22). To obtain comparable catchment (in years)=ÓDi; cumulative level of areas, controls were patients with cancers exposure=ÓLi Pi Di. requiring the same medical environment as the To calculate the cumulative level, quantita- cases. The following sites were selected: rectum tive values (midpoints of the intervals) were or anal canal (n=30), liver or gall bladder assigned to each category of level and probabil- (n=15), pancreas (n=11), haematopoietic sys- ity (table 1). tem (n=34), bones and cartilage (n=7), skin (melanoma) (n=18), soft tissue (n=11), pros- DATA ANALYSIS tate (n=63), testis (n=17), bladder (n=29), Each substance was studied independently. other urinary organs (n=27), brain and nerv- Separate analyses were conducted for cancers ous system (n=18), thyroid (n=18), colon of the larynx and hypopharynx. Each analysis (n=5), and stomach (n=2). used the same control group. Occupational physicians specially trained for Occupational exposure was first assessed by this study interviewed both cases and controls a dichotomous variable ever versus never and collected detailed data about demographic exposed. Quantitative exposure variables were characteristics, alcohol and tobacco consump- converted into categorical variables according tion, and lifetime occupational history. A more to their distribution among all subjects. The complete description of the study design and of number of classes ranged from two to four, depending on the frequency of exposure. The the characteristics of cases and controls has http://oem.bmj.com/ previously been published.25 reference category for each analysis was the Of the 833 subjects included in the study, never exposed subjects. some were excluded from the analysis: those Table 1 Categories for level and probability of exposure with cancer at more than one site (n=7), those defined in the JEM for the studied substances and assigned who did not answer the questions on alcohol values (five cases of laryngeal cancer), and those who did not drink at all (nine controls, 14 cases of Level categories Probability categories Cut oV laryngeal cancer, five cases of hypopharyngeal on October 2, 2021 by guest. Protected copyright. Cut oV Assigned points Assigned cancer, because it was unclear whether they Substances points* value (%) value were teetotal or former drinkers who had stopped for health reasons). The final analysis Leather dust Low 1.00 10–50 0.30 Medium 2.00 50–90 0.70 thus included 793 subjects: 296 controls, 201 High 3.00 >90 1.00 men with hypopharyngeal cancer, and 296 Wood dust <1 0.50 10–50 0.30 with laryngeal cancer.
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