Smoking, alcohol drinking, occupational exposures and social inequalities in hypopharyngeal and laryngeal cancer

Gwenn Menvielle, Danièle Luce, Paquerette Goldberg and Annette Leclerc

Institut National de la Santé et de la Recherche Médicale, Unité 88-IFR69, Saint-Maurice, France

Correspondence: Gwenn Menvielle, INSERM Unité 88, Hôpital National de Saint-Maurice, 14 rue du Val d'Osne, F-94415 Saint-Maurice Cedex, France. E-mail: Gwenn.Menvielle{at}st-maurice.inserm.fr


    Abstract
 Top
 Abstract
 Methods
 Results
 Discussion
 References
 
Background Social inequalities with regard to hypopharyngeal and laryngeal cancers are observed in many countries. Differences in alcohol and tobacco consumption are often proposed as an explanation for this finding. The aim of this work was to determine the extent to which alcohol and tobacco consumption, and occupational exposure, explain these inequalities.

Methods A hospital-based case-control study included 504 male cases (105 with glottic, 80 with supraglottic, 97 with epilaryngeal, and 201 with hypopharyngeal cancers) and 242 male controls with non-respiratory cancers. Information about sociodemographic characteristics, detailed alcohol and tobacco consumption, educational level, and occupational history were collected. Odds ratios (OR) and their 95% CI were computed using logistic regressions.

Results When controlling for age only, laryngeal and hypopharyngeal cancers were strongly associated with educational level (OR for low versus high level = 3.22, 95% CI: 2.01, 5.18) and with all indicators based on occupation (OR for ever versus never manual worker = 2.54, 95% CI: 1.78, 3.62). When adjusted for alcohol and tobacco consumption, the OR decreased, but remained significant for occupation (OR for ever manual worker = 1.91, 95% CI: 1.23, 2.95). After further adjustment for occupational exposures, significant associations were no longer observed. Associations differed between subsites.

Conclusions Social inequalities observed for these cancers are not totally explained by alcohol and tobacco consumption; a substantial proportion could be attributable to occupational exposures.


Keywords Educational status, social class, laryngeal and hypopharyngeal neoplasm, alcohol consumption, smoking, occupational exposure

Accepted 4 December 2003

Laryngeal and hypopharyngeal cancers, which principally affect men, are considered rare in most European countries and in the US. The annual incidence rates for French men, however, are particularly high.1 Alcohol and tobacco are the principal risk factors for these cancers.2 Some dietary components and occupational exposures are also risk factors but to a lesser extent.3,4

Social inequalities have been observed for these cancers.5 Regardless of the social indicator considered, studies report significantly elevated risks among disadvantaged populations.6–13 Although alcohol and tobacco consumption are often cited as a possible explanation for the higher risks among lower social classes, not all studies have adjusted for these variables.12 Moreover, the studies that have adjusted for them used relatively crude coding and reached contradictory results: some observed significant associations6,8,11 while others did not.7,9 Thus, whether alcohol and tobacco consumption totally explain social inequalities for these cancers remains a controversial question. Occupational exposures may also explain some of these social inequalities, but no study has examined this hypothesis.

The aim of this study was to consider the social inequalities in the risk of laryngeal and hypopharyngeal cancers and to determine the extent to which alcohol and tobacco consumption, and occupational exposures, explain them. We used data from a case-control study conducted in France. Previous analyses of these data focused on occupational risk factors and found elevated risks for some occupations14 and for exposure to asbestos,15 formaldehyde, and coal dust.16


    Methods
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 Abstract
 Methods
 Results
 Discussion
 References
 
This case-control study was conducted in 15 French hospitals in 6 cities. The study design has been described elsewhere14 and will be only briefly summarized here. Cases were all men diagnosed with primary squamous cell tumours of the larynx or hypopharynx in these hospitals between 1989 and 1991. Among the 664 cases initially identified, 136 (20.5%) were not interviewed (11 died before the interview, 40 for health reasons, 63 could not be located, 22 refused). Controls were men with primary non-respiratory cancers, selected by frequency matching for age, in the same hospitals as the cases or in similar nearby hospitals. Among the 355 eligible controls, 50 (14%) could not be interviewed (14 for health reasons, 22 could not be located, 14 refused). To obtain comparable catchment areas for cases and controls, the controls were patients with types of cancer requiring the same medical environment as the cases. The following sites were selected: rectum or anal canal (n = 30), liver (n = 14), gall bladder (n = 1), pancreas (n = 11), haematopoietic system (n = 34), bones and cartilage (n = 7), skin melanoma (n = 18), soft tissue (n = 11), prostate (n = 63), testis (n = 17), bladder (n = 29), other urinary organs (n = 27), brain and nervous system (n = 18), thyroid (n = 18), colon (n = 5), and stomach (n = 2).

Trained interviewers met subjects in person. The questionnaire asked about sociodemographic characteristics, alcohol and tobacco consumption, dietary habits, and complete job history. Each job was coded using the International Standard Classifications for Occupation (ISCO)17 and Industry (ISIC).18 Occupational exposure to several agents (silica, asbestos, man-made vitreous fibres, formaldehyde, coal dust, textile dust, flour dust, wood dust, and leather dust) was assessed with a job-exposure matrix (JEM) developed earlier for a study on sinonasal cancer by experts with extensive experience in assessing occupational exposures in epidemiological studies, and described in detail elsewhere.19 For each occupation/ industry combination and for each substance, the JEM gives the probability of exposure and the level of exposure. Industrial hygiene data were used to determine semi-quantitative indices of exposure.

The following subjects were excluded from the analysis: 6 who did not answer the questions on alcohol (5 laryngeal cancers) or tobacco (1 control) and 28 who did not drink at all (9 controls, 5 cases with hypopharyngeal cancer and 14 with laryngeal cancer) because it was not clear if they were teetotallers or former drinkers who had stopped for health reasons. Controls with bladder, liver, or pancreas cancer were excluded from the analysis because alcohol or tobacco are known risk factors for these cancer sites. The analyses finally concerned 746 men (504 cases and 242 controls). The 504 cases included 201 hypopharyngeal cancers, 296 laryngeal cancers, and 7 men with both sites affected. We distinguished the anatomical subsites for the larynx according to the classification used by Tuyns et al.2: 97 cancers of the epilarynx, 80 cancers of the supraglottis, 102 cancers of the glottis, 3 cancers of the subglottis, and 14 cancers of the larynx unspecified.

We used several variables to characterize socioeconomic status. Educational level was considered as a categorical variable with three classes: low (<5 years of education), intermediate, and high (≥12 years). Occupational class was classified according to the Erikson and Goldthorpe scheme,20 using a conversion tool developed for the ISCO code.21 A collapsed version of the original 11-category Erikson, Goldthorpe, and Portocarero (EGP) classification was used: non-manual workers (EGP classes I to IVb), manual workers (EGP classes V to VIIa), and agricultural workers (EGP classes IVc and VIIb). This classification in three categories has been used in several European studies of socioeconomic inequalities in health.22–24 Subjects were classified in these categories according to their occupation at several points in time: first job held, last job held, longest job held and ever employment in each class. Occupational mobility was considered as a categorical variable in six classes according to occupational class at the beginning and the end of the career: stable non-manual, stable manual, stable agricultural, upward occupational mobility (from manual to non-manual worker), downward occupational mobility (from non-manual to manual), and other. To assess which factors might explain social inequalities, we calculated the odds ratios (OR) associated with the different socioeconomic indicators and their 95% CI for three different models: adjusted for age only; adjusted for age and alcohol and tobacco consumption; adjusted for age, alcohol and tobacco consumption, and occupational exposures.

Age was treated as a categorical variable (<50 years, 50–59 years, 60–69 years, ≥70 years). We paid special attention to modelling the effects of alcohol and tobacco consumption, in order to best characterize the relationship between these risk factors and laryngeal/hypopharyngeal cancer risk and to select the model that was best suited for confounding adjustment. A first set of analyses with logistic regressions determined the most relevant variables. The following variables were considered: smoking status, cumulative tobacco consumption in pack-years, daily amount of tobacco smoked, duration of smoking, age at initiation, duration since quitting, type of tobacco (black or blond, use of filter, cigarettes, pipes, cigars, hand rolled cigarettes), daily alcohol consumption, type of alcohol. Continuous variables were treated alternatively as quantitative or ordinal or converted into categorical variables according to their distribution among controls. Interaction terms were also tested. Several models including different variables were compared in order to select the model that produced the largest likelihood with the fewest number of parameters. The model we selected included alcohol consumption as an ordinal variable coded 0 for <1 glass per day, 1 for 1–2 glasses, 2 for 3–4 glasses, 3 for 5–8 glasses, 4 for 9–12 glasses, and 5 for ≥13 glasses; smoking indicators as categorical variables: smoking status (never-smoker, current smoker, ex-smoker), amount of tobacco smoked (never-smoker, 1–9 g daily, 10–19 g daily, 20–39 g daily, ≥40 g daily), duration of smoking (never-smoker, <30 years, 31–40 years, >40 years).

Previous analyses of these data have investigated the relation between occupational exposures and laryngeal/hypopharyngeal cancer risk.15,16 We included in the models the occupational exposures significantly associated with cancer risk (asbestos, coal dust, and formaldehyde). For each selected substance, several exposure variables were assessed (exposed/non exposed, cumulative level, and probability of exposure) in order to select a model that represented the effects of occupational exposures with the fewest number of parameters. Finally, exposure to asbestos and coal dust were introduced as dummy variables (exposed/non-exposed) and exposure to formaldehyde as a categorical variable (probability of exposure <0.1, 0.1–0.5, >0.5).

The proportion of social inequalities explained by alcohol and tobacco was estimated by calculating a percentage change in OR with the following index: (OR1–OR2)/(OR1–1), where OR1 is the OR adjusted for age only and OR2 is the OR adjusted for age and alcohol and tobacco consumption. This index was also used to estimate the contribution of occupational exposures to social inequalities. When the index was >1, it was set to 1. The overall analyses were conducted with unconditional logistic regression, and the subsite analysis with unconditional polytomous logistic regression, which enabled a comparison of the OR between four subsites:25 the glottis (the three cases of subglottic cancer were grouped with the glottic cancers), the epilarynx, the supraglottis, and the hypopharynx. SAS software version 8.2 was used for the analyses.


    Results
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 Abstract
 Methods
 Results
 Discussion
 References
 
Table 1 summarizes the results for the overall population. When age was controlled for, significantly elevated OR were found for men who were manual workers in their first, last, or longest occupation, as compared with non-manual workers. Lower OR, while greater than 1, were found among agricultural workers. Ever employment in the category of manual workers was associated with a significant increase in risk, whereas a significantly lower risk was observed among ever non-manual workers. Statistically significant OR of about 2 were found for men stable as manual workers, for those downwardly mobile, and for those upwardly mobile, when compared with those stable in the group of non-manual workers. The risk of laryngeal and hypopharyngeal cancer increased when educational level decreased, and significantly elevated OR were observed for men with intermediate and low educational levels.


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Table 1 Laryngeal/hypopharyngeal cancer risk according to several socioeconomic variables (501 cases and 242 controls)

 
When alcohol and tobacco consumption were also taken into account, OR decreased. They remained >1 for manual workers, and were statistically significant for manual workers in the first occupation and for ever manual workers. OR around unity were found among agricultural workers. No significant association subsisted for ever non-manual workers. The OR associated with educational level were no longer significant, although they still increased as educational level decreased.

When occupational exposures were introduced into the models, the OR decreased and no significant relations were observed. The OR nonetheless remained >1 for the lowest social categories.

In all of the models, the strongest associations among the occupationally related socioeconomic indicators were found for any employment as a manual worker. Occupational mobility did not seem to have a strong effect on cancer risk.

Table 2 presents the results of the analysis by subsite, limited to educational level and occupation class of ever (versus never) manual worker. The lowest OR related to occupation were observed for glottic cancer, and no significant association was observed whatever the model. Significant elevated OR were found for the other subsites when controlling for age and for supraglottic and hypopharyngeal cancer when controlling for age, alcohol and tobacco consumption. When we also adjusted for occupational exposures, associations with occupation were no longer significant, although a twofold increase in risk subsisted for supraglottic and hypopharyngeal cancer. In the three models including educational level, the OR associated with educational level increased progressively from the glottis to the supraglottis, to the epilarynx and the hypopharynx. Once alcohol and tobacco consumption were taken into account, the OR associated with low educational level was at unity for glottic cancer, while those associated with supraglottic and epilaryngeal cancer remained >1 but were no longer significant; a significant threefold increased risk of hypopharyngeal cancer was found. When we also controlled for occupational exposures, the OR for hypopharyngeal cancer, although >2, was no longer significant.


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Table 2 Laryngeal/hypopharyngeal cancer risk according to occupation and educational level

 
For both occupation and educational level, the OR associated with glottic and hypopharyngeal cancer differed significantly when we adjusted for age, and for age and alcohol and tobacco, but not when occupational exposures were also considered.

We computed indices (described above, in Methods) to quantify the changes in the OR when alcohol and tobacco consumption, and occupational exposures, were introduced into the models. These indices, presented in Table 3, estimate the contribution of these factors to the differences observed for social indicators. The results differ strongly according to the subsite and variable considered. On the whole, alcohol and tobacco consumption explained about two-thirds of the differences observed for educational level, but this proportion varied substantially by subsite: about 50% for the epilarynx and hypopharynx, 75% for the supraglottis, whereas alcohol and tobacco completely explained the differences for glottic cancer. Occupational exposures explained about 50% of remaining inequalities. Thus, including occupational exposures increased the proportion of differences explained to 85% for all cases and for the supraglottis, and to about 75% for the epilarynx and hypopharynx.


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Table 3 Proportion of social differences for laryngeal/hypopharyngeal cancer risk explained by alcohol and tobacco and occupational exposures

 
Alcohol and tobacco consumption explained about 40% of the excess risk observed for manual workers, for all subsites. When occupational exposures were also taken into account for this indicator, about 40% of the remaining inequalities were explained for all cases, with strong disparities across subsites (between 5% and 60%). Thus approximately two-thirds of the global differences were explained; this proportion ranged from 39% for supraglottic cancer to 79% for epilaryngeal cancer.


    Discussion
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 Abstract
 Methods
 Results
 Discussion
 References
 
Our study shows the existence of wide social inequalities in the risk of laryngeal and hypopharyngeal cancer. These results suggest that alcohol and tobacco consumption do not totally explain these inequalities and that a substantial portion is explained by occupational exposures. We nonetheless continue to observe elevated OR among the lower social categories when we adjust for these factors.

The controls in our study were patients with cancer at various sites. The use of cancer controls has several advantages, particularly the reduction of recall bias. It may nonetheless present some problems, especially when risk factors are similar for case and control diseases.26 To minimize this problem, we excluded cancer sites known to be related to alcohol or tobacco consumption and considered several different sites, each represented by a small sample. However, since those in lower social categories have a higher risk of cancer in general, the association between the risk of laryngeal and hypopharyngeal cancer and social indicators could have been underestimated. A formal evaluation of this bias was impossible because the source population of the cases in this hospital-based study is unknown. Nevertheless, to have an order of magnitude of this potential bias, we compared the proportion of manual workers among the controls to the French population in the same geographical areas. Data from the 1968, 1975, and 1982 French censuses were converted into the EGP classification using an available conversion algorithm.20 Percentages were standardized for age (indirect method). In our sample 48.5% of controls were manual workers in 1968 compared with 46.8% in the French population (P = 0.32). The corresponding comparison for 1975 was 46.1% versus 44.7% (P = 0.33) and for 1982, 42.1% versus 41.0% (P = 0.88). The distribution of social class in the control series thus appears to be close to that of the general population, and underestimation of the association with social indicators, if any, is probably not substantial.

In this study social status was measured by educational level and occupational class. Educational level is an indicator easy to measure and stable throughout life, and can be interpreted as an indicator of social situation during childhood.27 The EGP scheme we applied for occupational class is a relatively commonly used indicator.22–24 However, we used three groups which are not clearly hierarchical. Some heterogeneity is observed within manual and non-manual classes. Both classes may overlap in terms of socioeconomic status, particularly because the distinction between routine non-manual workers and skilled manual workers is not always obvious. However, these problems would occur with any socioeconomic status index that divides the population in few broad groups, and the size of our study did not allow us to use a more precise classification.

Few studies have addressed the issue of social inequalities for cancers of the upper aerodigestive tract (UADT). As in the present study, strong inverse associations with social indicators have been observed when controlling for age alone.7–9,12 Differences in tobacco and alcohol consumption levels, both higher in lower social classes, would lead to higher risks in these classes: this is often proposed as an explanation for this finding. In our study, however, when alcohol and tobacco consumption were introduced into the models, social inequalities decreased but did not totally disappear. Significantly elevated OR were still associated with low educational level and employment as manual worker. These results are controversial in the literature. After adjustment for alcohol and tobacco consumption, some studies6–8,11—but not all9—still observe a significant association. However, in most studies, this adjustment is crude and residual confounding cannot be excluded. In our study we devoted special efforts to adjusting for smoking and alcohol in the analyses, but residual confounding, although probably small, is still possible.

People who are upwardly (resp. downwardly) mobile could have been in better (resp. poorer) health than people in the social category they left. This phenomenon has been observed for several diseases,28 but has been little studied in cancer incidence. A study of workers in a large French company found significantly higher risks of UADT cancer among men who were not upwardly mobile,10 but alcohol and tobacco consumption were not adjusted for. In our study, no clear pattern was shown in the analysis of occupational mobility. Ever employment as manual worker appeared to be the most important risk factor.

To our knowledge, only one study has analysed the association between socioeconomic status and the risk of UADT cancer by subsite.11 After adjustment for alcohol and tobacco, the authors found significantly elevated OR associated with low socioeconomic status for pharyngeal and supraglottic cancer but not for glottic cancer. These results are consistent with ours: we found no relation for glottic cancer but social inequalities persisted for the other subsites after controlling for alcohol and tobacco consumption.

In our study, adjustment for occupational exposures strongly decreased social inequalities for all subsites except supraglottic cancer. This result may be explained by the findings in previous analyses of these data that occupational exposures were associated mainly with hypopharyngeal and epilaryngeal cancers.15,16 We could not reject the hypothesis that socioeconomic status overlaps with occupational exposures. Nevertheless, given the heterogeneity of the manual class, occupational exposures certainly highly vary within this class. Occupational exposures were assessed with a JEM, and some misclassification of exposure is likely to have occurred. Assessment of exposures was however independent of case/control status. Such non-differential misclassification would bias the OR towards unity, and a positive residual confounding may remain when the exposures are introduced in the models with social class. Then the proportion of social differences explained by occupational exposures may have been underestimated. Only occupational exposures significantly associated with cancer risk were included in the models. As a check for residual confounding, other occupational exposures existing in the JEM were included in the models, but this did not materially affect the risk estimates associated with social class. On the other hand, information on occupational exposure to some known or suspected carcinogens for laryngeal and hypopharyngeal cancer, such as strong acids, polycyclic aromatic hydrocarbons, or solvents was not available. Some of these may explain part of the residual differences, and this also may have led us to underestimate the contribution of occupational exposures to social inequalities. Nevertheless occupational exposures seemed to explain between 20 and 30% of the social inequalities in our study, depending on the social indicator. The proportion of social differences attributable to occupational exposures has been previously estimated at one-third for all cancers, 50% for lung cancers and 5% for laryngeal cancers.29 This estimation was based on the proportion of cancer attributable to occupational exposures proposed by Doll and Peto in 1981,30 but no study of UADT cancers has estimated the portion of the social inequalities attributable to occupational exposures directly.

Several studies have shown an association between diet and the risk of UADT cancer.31 Information on dietary habits was not available in our study. Dietary factors, which are correlated with socioeconomic status, may explain part of residual inequalities.

These data were collected in the 1990s. The incidence of these cancers is currently diminishing, and the situation concerning social inequalities has probably changed somewhat. An Italian study limited to oesophageal, oral cavity and pharyngeal cancers compared two series of data collected during 1984–1992 and 1992–1997. The old data revealed social inequalities, even when controlling for alcohol and tobacco consumption, but these inequalities did not persist in the recent data.32 The situation in France is unknown since no similar study has been conducted with recent data.

This study shows that alcohol and tobacco, the main risk factors for laryngeal and hypopharyngeal cancers, do not totally explain social inequalities with regard to these tumours. Our data suggest that occupational exposures may explain a substantial portion of them. Some inequalities nonetheless remain when these factors are considered; differences observed between subsites suggest that separate analyses should be conducted according to subsite. Further studies are needed to explore what might explain the residual inequalities.


KEY MESSAGES

  • In France, there are social inequalities in the risk of hypopharyngeal and laryngeal cancer.
  • Alcohol and tobacco explain a large part, but not all, of the social inequalities for hypopharyngeal and laryngeal cancer.
  • Occupational exposures seem to explain a portion of the remaining inequalities—between 20 and 30% of the total.2

 


    Acknowledgments
 
Gwenn Menvielle received a grant from the Fondation de France for this work.


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 Methods
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 Discussion
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