In vitro susceptibility of Aspergillus spp. clinical isolates to albendazole.

The in vitro antifungal activity of albendazole, a benzimidazole widely used as an antihelmintic drug in humans, was investigated and assessed for its activity against Aspergillus spp. Forty-eight isolates, representing the most frequent species found in human pathology [Aspergillus fumigatus (n = 27), Aspergillus flavus (n = 10), Aspergillus terreus (n = 7), Aspergillus nidulans (n = 3) and Aspergillus niger (n = 1)], and one quality control strain (A. niger ATCC 9804 83435) were tested according to the NCCLS M38-P methodology for moulds. All the strains were susceptible to albendazole, with homogeneous MICs for each species; three strains were resistant to itraconazole.

Inter-strain variability of insertion/deletion events in the Encephalitozoon cuniculi genome: a comparative KARD-PFGE analysis.

We applied a two-dimensional pulsed-field gel electrophoresis procedure to the genomes of two karyotype variants assigned to two different strains of the microsporidian Encephalitozoon cuniculi, termed D (strain III) and F (strain II). Data obtained for BssHII and MluI restriction fragment length polymorphisms in each chromosome are compiled and compared to the reference strain I variant A. Six Insertion/Deletion (InDels) are found in subterminal position, some of these being characteristic of either D or F. Like in strain 1, the terminal fragments extending between each telomere and rDNA locus are conserved in length for each chromosome. They are however smaller than in reference variant. This size reduction is estimated to be 2.5 kbp for the strain III isolate and 3.5 kbp for the strain II isolate. We hypothesize that for the three E. cuniculi strains, all chromosome extremities are prone to a constant process of sequence homogenization through mitotic recombination between conserved regions.

Laryngeal and hypopharyngeal cancers and occupational exposure to formaldehyde and various dusts: a case-control study in France.

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 dose-response 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.

Occurence of subtelomeric rearrangements in the genome of the microsporidian parasite Encephalitozoon cuniculi, as revealed by a new fingerprinting procedure based on two-dimensional pulsed field gel electrophoresis.

In Microsporidia, mitochondria-lacking eukaryotic intracellular parasites, genomic comparisons were so far based on molecular karyotyping. The mammal-infecting species Encephalitozoon cuniculi is characterized by a very low haploid genome size (approximately 2.8 Mbp) and rather high karyotype variability. Recently, we developed a two-dimensional pulsed field gel electrophoresis (2-D PFGE) fingerprinting technique useful for constructing a restriction map fo the genome of a mouse E. cuniculi isolate (karyotype variant A). The so-called karyotype and restriction display 2-D PFGE (KARD-PFGE) protocol involved 1-D chromosome separation, digestion with a rare cutter, Klenow radiolabeling of genomic DNA and 2-D separation of restriction fragments followed by autoradiography. In order to assess its suitability for detecting polymorphic loci in E. cuniculi, we applied KARD-PFGE with either BssHII or Mlul digestion to genome analysis of two rabbit isolates representative of two different karyotype variants (A and C). The 2-D spot pattern of the rabbit isolate variant A is identical to the reference mouse isolate but differs greatly from the rabbit isolate variant C. Chromosomal restriction fragment length polymorphisms (RFLPs) provide strong evidence for homologous chromosomes and frequent DNA rearrangements within subtelomeric regions just upstream of the dispersed rDNA units closely associated with each chromosomal end.

Laryngeal and hypopharyngeal cancer and occupational exposure to asbestos and man-made vitreous fibers: results of a case-control study.

BACKGROUND: The data from a case-control study performed in France between 1989 and 1991 were used to test whether exposure to either asbestos or to man-made vitreous fibers (MMVF) is a risk factor for cancer of the larynx or the hypopharynx. METHODS: This study involved 315 incident cases of laryngeal cancer, 206 cases of hypopharyngeal cancer, and 305 hospital-based controls with other types of cancer, all recruited in 15 hospitals in six French cities. The subjects' past occupational exposure to asbestos and to four types of MMVF (mineral wool, refractory ceramic fibers, glass filaments, and microfibers) was evaluated based on their job history, with the aid of a job-exposure matrix. Odds ratios were calculated with unconditional logistic regression, with adjustment for smoking and drinking levels. RESULTS: Exposure to asbestos resulted in a significant increase in the risk of hypopharyngeal cancer (OR = 1.80, 95% CI: 1.08-2.99) and a nonsignificant increase in the risk of laryngeal cancer (OR = 1.24, 95% CI: 0.83-1.90). Risk was highest for the epilarynx (highest cumulative level of exposure: OR = 2.22, 95% CI: 1.05-4.71). Exposure to mineral wools was of borderline significance for the risk of hypopharyngeal cancer (OR = 1.55, 95% CI: 0.99-2.41), and nonsignificantly associated with the risk of laryngeal cancer (OR-1.33, 95% CI: 0.91-1.95). The risk was again highest for the epilarynx (OR = 1.85, 95% CI: 1.08-3.17). No significant results were observed for the other MMVF. CONCLUSIONS: These results suggest that asbestos exposure increases the risk of epilaryngeal and hypopharyngeal cancers. It is difficult to reach a conclusion about the effects of mineral wools, because nearly all the exposed subjects were also exposed to asbestos. The possible effects of other MMVF were difficult to assess in this study, because of the paucity of exposed subjects.

Encephalitozoon cuniculi (Microspora) genome: physical map and evidence for telomere-associated rDNA units on all chromosomes.

A restriction map of the 2.8-Mb genome of the unicellular eukaryote Encephalitozoon cuniculi (phylum Microspora), a mammal-infecting intracellular parasite, has been constructed using two restriction enzymes with 6 bp recognition sites (Bss HII and Mlu I). The fragments resulting from either single digestions of the whole molecular karyotype or double digestions of 11 individual chromosomes have been separated by two-dimensional pulsed field gel electrophoresis (2D-PFGE) procedures. The average distance between successive restriction sites is approximately 19 kb. The terminal regions of the chromosomes show a common pattern covering approximately 15 kb and including one 16S-23S rDNA unit. Results of hybridisation and molecular combing experiments indicate a palindromic-like orientation of the two subtelomeric rDNA copies on each chromosome. We have also located 67 DNA markers (clones from a partial E. cuniculi genomic library) by hybridisation to restriction fragments. Partial or complete sequencing has revealed homologies with known protein-coding genes for 32 of these clones. Evidence for two homologous chromosomes III, with a size difference (3 kb) related to a subtelomeric deletion/insertion event, argues for diploidy of E.cuniculi. The physical map should be useful for both the whole genome sequencing project and studies on genome plasticity of this widespread parasite.

In-gel DNA radiolabelling and two-dimensional pulsed field gel electrophoresis procedures suitable for fingerprinting and mapping small eukaryotic genomes.

A simple method for complete genome radiolabelling is described, involving long-wave UV exposure of agarose-embedded chromosomal DNA and [alpha-(32)P]dCTP incorporation mediated by the Klenow fragment. Experiments on the budding yeast genome show that the labelling procedure can be coupled with two new two-dimensional pulsed field gel electrophoresis (2D-PFGE) protocols of genome analysis: (i) the KARD (karyotype and restriction display)-PFGE which provides a complete view of the fragments resulting from a single restriction of the whole genome and (ii) the DDIC (double digestion of isolated chromosome)-PFGE which is the eukaryotic counterpart of complete/complete 2D-PFGE in bacterial genomics.

[Standards, options and recommendations (SOR) for clinical care of squamous cell carcinoma of the oropharynx. Groupe de travail SOR]. / Standards, Options et Recommandations pour la prise en charge des patients atteints de cancer épidermoïde de l'oropharynx.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the management of squamous carcinoma of the oropharynx. METHODS: Data have been identified by literature search using Medline (1991-1998) and the expert groups personal reference lists. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for squamous cell carcinoma of the oropharynx management are that: 1) diagnosis and initial assessment should be based on appropriate clinical and radiological findings; 2) the therapeutic strategy is based on surgery, radiotherapy, bradytherapy and chemotherapy; 3) in limited tumours, the recommended strategy involved the use of one of these modality; 4) a multimodality approach is recommended for the treatment of extended resectable tumours. Following results of recent meta-analyses, use of neo-adjuvant chemotherapy is not recommended. The same studies have shown that association of chemotherapy and radiotherapy either in sequence or in combination significantly improve survival of extended curable tumours. These associations are recommended within the framework of clinical trials; 5) follow-up of squamous carcinoma of the oropharynx should involve physical examination of the upper aerodigestive tract and the lymph nodes areas every three months during the first year, every six months during the second year and then every year. An annual chest x-ray is recommended. Other investigations should be performed as indicated by symptoms and clinical manifestations.

Laryngeal and hypopharyngeal cancer and occupation: results of a case control-study.

OBJECTIVES: To ascertain whether certain occupations are associated with laryngeal or hypopharyngeal cancer. METHODS: A hospital based case-control study was carried out in 15 hospitals in France. It included 528 male cases diagnosed between January 1989 and April 1991, and 305 male controls with various other types of cancer. Interviews were carried out to obtain lifetime job histories and information on potential confounders. Logistic regression was used to compute the odds ratios (OR) for each of about 80 occupations and industries. RESULTS: There was an excess risk of laryngeal and hypopharyngeal cancer among service workers (OR 2.2, 95% confidence interval (95% CI) 1.3 to 3.9), agricultural and animal husbandry workers (OR 1.6, 95% CI 0.9 to 2.8), miners and quarrymen (OR 2.0, 95% CI 0.9 to 4.3), plumbers and pipe fitters (OR 2.6, 95% CI 0.8 to 8.1), glass formers and potters (OR 4.3, 95% CI 1.0 to 18) transport equipment operators (OR 1.5, 95% CI 1.0 to 2.5), and unskilled workers (OR 1.7, 95% CI 1.0 to 2.9). Analysis by industrial branch showed an excess risk for coal mining (OR 2.1, 95% CI 1.1 to 4.1), manufacture of metal products (OR 1.9, 95% CI 1.0 to 3.3), and administration and sanitary services (OR 1.7, 95% CI 1.1 to 2.5). CONCLUSION: These results suggest that occupational exposure might have a role in generating laryngeal and hypopharyngeal cancer, and indicate the need for further evaluation of these findings, an for the identification of the carcinogens which might account for the excess risks found for certain occupations.

Anemia is associated with lower local-regional control and survival after radiation therapy for head and neck cancer: a prospective study.

PURPOSE: To evaluate the prognostic value of anemia in squamous cell carcinomas in the head and neck treated with curative radiation therapy alone. MATERIALS AND METHODS: In a prospective study, the hemoglobin level was measured prior to radiation therapy in 217 patients (188 [87%] men and 29 [13%] women) with cancer of the oral cavity (n = 61 [28%]), oropharynx (n = 53 [24%]), hypopharynx (n = 21 [10%]), and larynx (n = 82 [38%]). Anemia, defined as hemoglobin level below 13.5 g/dL in men and below 12.0 g/dL in women, was diagnosed in 58 (31%) of the men and five (17%) of the women. Median follow-up was 29 months (range, 2-63 months). RESULTS: The 2-year actuarial probability of local-regional control was 69% (95% confidence interval, 63%, 76%). Multivariate analysis showed the relative risk of failure of local-regional control to increase for stage T3 and T4 tumors (1.8 [95% confidence interval, 1.1, 3.1]), stage N3 nodes (3.6 [95% confidence interval, 1.8, 7.1]), weight loss (2.2 [95% confidence interval, 1.3, 4.0]), and anemia (1.6 [95% confidence interval, 1.0-2.7]). The relative risk of death increased for stage T3 and T4 tumors (2.5 [95% confidence interval, 1.4, 4.3]), N3 nodes (4.0 [95% confidence interval, 1.0, 7.9]), oral cavity tumors (2.0 [95% confidence interval, 1.2, 3.2]), male sex (4.1 [95% confidence interval, 1.3, 13.1]), weight loss (2.2 [95% confidence interval, 1.3, 3.7]), and anemia (1.7 [95% confidence interval, 1.03, 2.7]). CONCLUSION: Moderate anemia appeared to be an independent prognostic factor in squamous cell carcinoma of the head and neck treated with radiation therapy alone.

Nodal failures in patients with NO N+ oral squamous cell carcinoma without capsular rupture.

BACKGROUND: The efficacy of postoperative irradiation of the neck after lymph node dissection in terms of prevention of cervical node recurrence (NR) has not been demonstrated in patients with NO squamous cell carcinoma of the oral cavity. METHODS: This multicenter retrospective analysis comprises 826 patients with squamous cell carcinoma of the oral cavity, all clinically NO. The primary tumor was treated by resection or brachytherapy. All patients underwent cervical dissection adapted to the site of the tumor. Fourty seven N+ patients with capsular rupture were excluded; 160 patients were N+ without capsular rupture (N+ CR-), and 619 were N-. Postoperative cervical irradiation was performed in 67 of 160 N+ CR- patients and in 49 of 619 N- patients. RESULTS: NR developed in 78 patients, associated with local recurrence in 33 cases and isolated in 45 cases. Twenty-six of the 45 cases of isolated NR occurred in the 619 N- patients (4%), and 19 occurred in the 160 N+ CR- patients (12%, p = .001). The 26 NR observed in the N- patients occurred in nonirradiated patients. Among the 19 NR observed in the N+ CR- patients, the incidence of recurrence was not significantly different between irradiated patients (6 NR of 67.9%) and nonirradiated patients (13 NR of 93, 14%). NR rates also did not differ according to the number of lymph nodes invaded nor according to the level of the positive nodes; 14 of 45 isolated NR occurred in a nondissected suprahyoid region. Of 779 patients, 255 (33%) subsequently developed a metachronous cancer; 153 upper respiratory and digestive tract tumors, 37 lung tumors, 33 esophageal tumors, and 32 other tumors. Isolated cervical failure was responsible for 40 deaths. CONCLUSION: The low NR rate in NO N+ CR- patients means that postoperative irradiation can be confined to N+ CR+ patients and, as a precautionary measure, to patients with more than 3 N+ CR-. Keeping irradiation in reserve allows the treatment of metachronous cancers, which are particularly frequent in these patients, in whom the 5-year survival rate is 54% in N+ CR- and 69% in N-.

[Surgery of the oropharynx after radiotherapy]. / Chirurgie de l'oropharynx après radiothérapie.

Over 40 years after the first commando procedures performed by M Dargent, surgical techniques such as mandibulotomy and myocutaneous flaps yield important changes in oropharyngeal surgery after definitive radiotherapy. Wide resections and simultaneous neck dissection are possible with good functional results. From 1970 to 1990, 250 patients with a carcinoma of the oropharynx were operated on after radiotherapy, 163 because of failure or complication of irradiation, 87 for a metachronous carcinoma occurred in an previously irradiated field. The postoperative mortality rate was 6%. The risk of carotid blow-up did not increase with the extension of the resection. Survival rates at 1, 3 and 5 years are 55%, 22%, 16% in salvage surgery and 69%, 36% and 24% in patients with metachronous cancer. Postoperative complications and failures in the primary and/or the neck account for 60% of causes of death. These results suggest that prior surgery of deeply ulcerative carcinoma of the oropharynx followed by radiotherapy is a better strategy than definitive radiotherapy with salvage surgery in reserve.

[Surgery of the hypopharynx after radiotherapy]. / Chirurgie de l'hypopharynx après radiothérapie.

Changes in surgical procedures for hypopharynx cancer after definitive radiotherapy are important since the use of pedicled myocutanous flaps and free digestive transplants. Postoperative course is improved and salvage surgery more frequent. From 1970 to 1990, 160 hypopharyngeal carcinomas were operated on after radiotherapy, 103 due to failures or complications after definitive irradiation and 57 metachronous cancers. During this period, the rate of lethal postoperative complications decreased from 25% to 8%. Crude survival rates are 51% at 1 year, 22% at 3 years and 15% at 5 years. Poor prognostic features are local extension, positive margins and extracapsular nodal spread. Postoperative deaths and failures in primary or neck account for 60% of the causes of death. Results of salvage surgery are unsatisfactory: the choice of definitive radiotherapy with surgery in reserve must be restricted to selected cases.

Prognostic value of tumor regression during radiotherapy for head and neck cancer: a prospective study.

OBJECTIVE: Prospective evaluation of tumor regression during external irradiation for head and neck squamous cell carcinomas and its association with long-term local control. METHODS AND MATERIALS: Two hundred twenty-eight patients with histologically confirmed squamous cell carcinoma [oral cavity: 59 (26%), oropharynx: 65 (29%), hypopharynx: 37 (16%), larynx: 67 (29%)] were included between January 1986 and December 1990. Curative intent external irradiation delivered 65-70 Gy over a period of 7 weeks (five 2 Gy fractions per week). Tumor regression was evaluated clinically and endoscopically every week. RESULTS: Tumor regression, assessed at 2 weeks, was as follows: no response: 62 (30%), 25% response: 121 (59%); 50% response: 23 (11%). At 5 weeks, 9 (4%) patients showed 0-25% regression, 75 (33%) showed 50% regression, 115 (50%) showed 75% regression, and 29 (13%) showed complete regression. Median follow-up was 79 months (range: 6-96 months). The local control probability was 68% (62-74%) at 2 years, 65% (59-70%) at 5 years. Univariate analysis showed that, at 2 weeks, local control was significantly different between the nonresponders and the patients with 25% or greater response (p < 0.025) and that, at the fifth week, local control was very different between the major responders (75 and 100%) and the minor responders (0-50%) (p < 0.0001). Multivariate analysis (Cox Proportional Hazards Model) showed that the probability of local relapse was significantly and independently increased for minor regression at 5 weeks [Relative risk (RR) of failure was 2.3 (1.4-3.7)], for nonlaryngeal tumors [RR: 2.4 (1.3-4.5)], and for Stage T3-T4 [RR:2.4 (1.4-4)]. Three prognostic groups can, therefore, be proposed: 1) low risk of recurrence when regression > or = 75% and laryngeal tumor or T1-T2 tumors in other sites: 106 (46.5%) patients, 2-year local control probability: 84% (77-92%); 2) high risk of recurrence: regression < or = 50% and T3-T4 nonlaryngeal tumors: 44 (19%) patients, 2-year local control probability: 27% (13-41%); 3) intermediate risk of recurrence: 78 (34.5%) patients, 2-year local control probability: 69% (58-80%). CONCLUSION: The present study suggests that tumor regression during external radiotherapy is an independent predictive factor of local control in head and neck carcinomas.

[Management of laryngeal cancers]. / Particularités des cancers du larynx.

With 5,000 cases yearly, laryngeal carcinomas account in France for the third of squamous cell cancers of the upper digestive and respiratory tract. The crude survival rate is 50% at 5 years. Carcinomas of vocal cords are often diagnosed as early stages if dysphonia leads the patients to the ENT specialist within 2 weeks. Cure of the primary is achieved in 90% of the early stages by radiotherapy with narrow fields or partial surgery, with a 80% 5 years survival rate. Advanced tumors are often treated by total laryngectomy and postoperative radiotherapy. Supra-glottic cancers (epiglottis) are more serious. Unilateral dysphagia or upper cervical neck node often delay early diagnosis. A total laryngectomy is the commonest treatment. The 5 years survival rate of 40% is due to local and/or regional failures and metachronous cancers in head and neck, and radiotherapy remains the two major treatments. Primary prevention is based upon suppression of tobacco and reduction of alcoholic consumption, secondary prevention on resection of leucoplakia and close follow-up of patients with chronic laryngitis.

Sinonasal cancer and wood dust exposure: results from a case-control study.

A case-control study of occupational risk factors for sinonasal cancer was conducted in France in 1986-1988. The study included 207 histologically confirmed cases and 409 controls. Among the male cases were 59 men with squamous cell carcinoma and 82 with adenocarcinoma. The risk of sinonasal cancer in relation to wood dust exposure was studied in these two groups. The analysis was based on a case-by-case assessment of exposure by an industrial hygienist. Hardwood and softwood were distinguished. An approximate twofold increase in risk for squamous cell carcinomas was observed for cases whose first exposure to either hardwood or softwood occurred before 1945; however, the two types of exposure were highly correlated. An exposure to wood dust--from either hardwood alone or hardwood and other kinds of wood--was found for all but two of the 82 male cases with adenocarcinoma. The effects of different elements of exposure to hardwood (duration, level, period) were studied in detail with a logistic model. Two components of exposure--duration and average level--contributed independently to the overall very elevated risk. Additional exposure to wood other than hardwood did not increase the risk.

[Occupational cancers: notification, compensation and prevention]. / Cancers professionnels: connaissance, réparation et prévention.

Less than 140 occupational cancers (OC) are compensated every year in France although the incidence is estimated for at least 6,000 new cases, as estimated by the epidemiologists (4% of the mortality by cancers). This situation can be explained by different factors: few compensation claims by the patients or families, frequent lack of interest from medical doctors for relation between cancer and work, occurrence of the OC after retirement, difficulty to distinguish the role of occupational factors from individual comportmental factors in many OC (for ex. a lung cancer hitting a smoker). The consequences of such a situation are multiple: no compensation for more than 95% of patients or relatives, taking for granted that OC is a minor problem, insufficient prevention of the carcinogenic factors on the work place, prevention of cancers restricted to individual comportmental changes. Physicians working in cancerology units have to incite their patients in notifying the OC and help them in compensation claims. They have also to ask for epidemiologic and toxicologic research when clusters of OC are identified in a plant, in order to get better prevention, compensation and regulations.

Sinonasal cancer and occupational exposure to formaldehyde and other substances.

A case-control study of cancer of the nose and paranasal sinuses was conducted in France to determine whether occupational exposure to formaldehyde was associated with an increased risk of sinonasal cancer. Exposures to 14 other substances or groups of substances were also studied (wood dust, leather dust, textile dust, flour dust, sugar dust, coal/coke dust, nickel compounds, chromium compounds, chromium VI, welding fumes, soldering fumes, cutting oils, paints and lacquers, glues and adhesives). Cases (n = 207) and controls (n = 409) were interviewed to obtain detailed information on job history and other potential risk factors for sinonasal cancer. In addition, a questionnaire specially designed for this study was used to help assess exposures to formaldehyde and other substances of interest. The questionnaires were translated into history of occupational exposure by an expert in industrial hygiene, without knowledge of case-control status. Several exposure variables (lifetime average level, duration, cumulative level) were used to describe the risk related to exposure to formaldehyde. Potential confounding factors (occupational and non-occupational) were examined and adjusted for when necessary. No significant association was found between exposure to formaldehyde and squamous-cell carcinomas of the sinonasal cavities. Because of the strong association between exposure to wood dust and nasal adenocarcinoma, it was not possible to assess an independent effect of formaldehyde on this type of cancer. However, among males exposed to medium or high levels of wood dust, the risk of adenocarcinoma associated with formaldehyde was significantly elevated for the highest exposure categories for average level (OR = 5.3, 95% confidence interval = 1.3-22.2), cumulative level (OR = 6.9, 95% CI = 1.7-28.2) and duration of exposure (OR = 6.9, 95% CI = 1.7-27.8). Although a residual confounding effect of wood dust could not be excluded, this study suggests that exposure to both formaldehyde and wood dust may increase the risk of nasal adenocarcinoma, by comparison with the risk due to wood dust alone. This study also indicated an increased risk among males who had been exposed to glues and adhesives, for all histologic types, which was not explained by a confounding effect of paints and lacquers, wood dust or formaldehyde. No other significant association was observed.