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Objectives-A case-control study was conducted in France to assess possible associations between occupational exposures and squamous cell carcinomas of the larynx and hypopharynx. Methods-The study was restricted to men, and included 201 hypopharyngeal cancers, 296 laryngeal cancers, and 296 controls (patients with other tumour sites). Detailed information on smoking, alcohol consumption, and lifetime occupational history was collected. Occupational exposure to seven substances (formaldehyde, leather dust, wood dust, flour dust, coal dust, silica dust, and textile dust) was assessed with a job exposure matrix. Exposure variables used in the analysis were probability, duration, and cumulative level of exposure. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were estimated by unconditional logistic regression, and were adjusted for major confounding factors (age, smoking, alcohol, and when relevant other occupational exposures). Results-Hypopharyngeal cancer was found to be associated with exposure to coal dust (OR 2.31, 95% CI 1.21 to 4.40), with a significant rise in risk with probability (p<0.005 for trend) and level (p<0.007 for trend) of exposure. Exposure to coal dust was also associated with an increased risk of laryngeal cancer (OR 1.67, 95% CI 0.92 to 3.02), but no doseresponse pattern was found. A significant relation, limited to hypopharyngeal cancer, was found with the probability of exposure to formaldehyde (p<0.005 for trend), with a fourfold risk for the highest category (OR 3.78 , 95% CI 1.50 to 9.49). When subjects exposed to formaldehyde with a low probability were excluded, the risk also increased with duration (p<0.04) and cumulative level of exposure (p<0.14). No significant association was found for any other substance. Conclusion-These results indicate that exposure to formaldehyde and coal dust may increase the risk of hypopharyngeal cancer. (Occup Environ Med 2000;57:767-773)

Occupational cohort studies are usually carried out without the benefit of information on smoking habits of cohort members. One common approach to avoid confounding bias related to smoking habits is to carry out an internal analysis, comparing workers with different degrees of occupational exposure. The premise behind this approach is that within a cohort there is unlikely to be correlation between degree of exposure and smoking habits. If this were untrue, smoking could confound the disease-exposure relationships. Our purpose was to verify the premise. The study sample consisted of 857 French-Canadian men born between 1910 and 1930, with 11 or fewer years of education, and interviewed around 1980 in the context of an occupational cancer case-control study. For each man we had information on smoking habits, job history, and a history of the chemicals he was exposed to in each of his jobs. We computed two indices of the dirtiness of workers' job histories: one based on the job titles held by the man and a second based on the degree of exposures to workplace substances. There was no correlation between these indices of job dirtiness and smoking history. We also examined the smoking-exposure relationship among the subsets of men who had been occupationally exposed to ten especially noticeable substances. Within the subsets, there was no indication of a consistent difference among the smoking subgroups in level or duration of exposure to these index substances. These findings do not support the view that nonsmokers sought out cleaner job environments than smokers; they imply that internal analyses of "dose-response" in cohort studies are unlikely to be seriously confounded by smoking habits.

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