Exposures to IARC Carcinogenic Agents in Work Settings Not Traditionally Associated with Sinonasal Cancer Risk: The Experience of the Italian National Sinonasal Cancer Registry.

The aim of this study is to highlight tasks and jobs not commonly considered at high risk for sinonasal cancer (SNC) identified by Regional Operating Centers currently active in the Italian National Sinonasal Cancer Registry (ReNaTuNS), which retrieve occupational histories through a standardized questionnaire. Data on exposures to IARC carcinogenic agents in work settings unknown to be associated with SNC risk were collected and analyzed. Out of 2,208 SNC cases recorded in the ReNaTuNS database, 216 cases and their worked exposure periods were analyzed. Unsuspected jobs with exposure to wood dust include construction-related tasks, production of resins, agriculture and livestock jobs (straw and sawdust), and heel factory work (cork dust). Other examples are hairdressers, bakers (formaldehyde), dressmakers, technical assistants, wool and artificial fiber spinners, and upholsterers (textile dusts). Moreover, settings with coexposure to different agents (e.g., wood with leather dusts and chromium-nickel compounds) were recognized. The study describes jobs where the existence of carcinogenic agents associated with SNC risk is unexpected or not resulting among primary materials employed. The systematic epidemiological surveillance of all epithelial SNC cases with a detailed collection of their work history, as performed by a dedicated population registry, is essential for detecting all potential occupational cases and should be considered in the context of forensic medicine and the compensation process.

Sinonasal cancer in a worker exposed to chromium in an unusual industrial sector.

BACKGROUND: Occupational exposure to chromium is carcinogenic for human respiratory system. Due to the low incidence of sinonasal malignancies, there is still a paucity of evidence to confirm that chromium(VI) exposure is a cause of nasal cancer. OBJECTIVES: To report on a sinonasal cancer (SNC) of rare occupational origin, increasing the awareness on epidemiological knowledge of occupational exposures to chromium compounds. METHODS: We describe a case of a 64-year-old chrome plater who worked in the galvanic industry in the early 1970s. After a latency period of 39 years, he was diagnosed with sinonasal undifferentiated carcinoma (SNUC). A brief review of the literature was conducted. RESULTS: A thorough occupational history revealed a 4-year-long occupational exposure to chromium(VI) during a magnesium cylinder plating process involved in computer production. The patient underwent endoscopic endonasal removal of the SNUC. He is alive with no evidence of disease at 40-month follow-up. Our literature review identified 8 papers concerning 40 cases of chrome-induced sinonasal tumors. The maximum relative risk of SNC developing in chromium-exposed workers was 15.4. CONCLUSIONS: When dealing with patients diagnosed with SNC, the possibility of an underlying occupational risk is worth further investigation. Because chromium exposure is rare, and the incidence of SNUC is low, any information emerging on clinical and exposure-related aspects of SNCs in chrome plating workers can contribute to adding evidence on the possible causal relationship between chromium and sinonasal malignancies.

Non-intestinal type sinonasal cancers and exposure to occupational carcinogens: a case-control study. / Tumori nasosinusali diversi da adenocarcinoma di tipo intestinale ed esposizione a cancerogeni professionali: uno studio caso-controllo.

BACKGROUND: Sinonasal cancers are rare, often fatal, tumors with a very high proportion of cases attributable to occupational exposures. The relevance of different carcinogens deeply varies among histological subtypes, with intestinal type adenocarcinomas (ITAC) characterized by a very large proportion of workers exposed to wood dust. The role of occupation in the etiology of other histotypes is less clear and more disputed, with authors questioning the possible occupational origin of non-ITAC cancers. METHODS: We conducted a hospital-based case-control study on 50 consecutives non-ITAC cancers and 50 controls, in Varese, Italy. Relative risks for previous exposure to carcinogens (any or single agent, i.e. wood/leather dust, solvents, metals) were calculated by multivariate logistic regression models adjusted for age, gender, smoking habits and residence (within or outside the Lombardy region). RESULTS: Having been exposed to any occupational carcinogen carried an OR of 3.04 (95%CI: 0.91-10.21). Considering single carcinogens, we observed no increased risk for wood dust exposure (OR=1.02, 95%CI: 0.21-4.94), while a large effect associated with previous exposure to other recognized carcinogens (leather dust, solvents or metals) appeared: OR=7.01 (95%CI: 1.51-32.8). DISCUSSION: Our results highlighted the importance of properly considering sinonasal cancers histological subtypes when investigating the role of occupational carcinogens. Grouping together all sinonasal cancers may end up in underestimating the role of wood in ITAC etiology as well as the relevance of other occupational exposures for non-ITAC tumors. All sinonasal cancers deserve a thorough investigation of the occupational history.

Secondary non-Hodgkin lymphoma of the ethmoid sinus after temozolomide.

The paranasal sinuses are rarely the site of malignancy, especially non-Hodgkin lymphoma. In such cases, the ethmoid sinus is the second most frequently involved paranasal sinus. Diagnosis of these malignancies is difficult because the early symptoms often mimic benign sinus pathology. Thus, most cases are diagnosed at an advanced stage, and their prognosis is poor. Here we describe the case of a 58-year-old man with a secondary high-grade B-cell non-Hodgkin lymphoma of the ethmoid sinus. This malignancy was diagnosed two years after the patient had received treatment with temozolomide for a glioblastoma multiforme. This case highlights that malignant tumours of the paranasal sinuses should always be included in the differential diagnosis of sinus disease. Additionally, patients treated with temozolomide should receive regular follow-up care including vigilant evaluation for secondary tumours, such as non-Hodgkin lymphoma.

[Wood dusts and neoplasms of the nose and paranasal sinuses: field investigations and laboratory experiments]. / Polveri di legno e tumori del naso e seni paranasali: indagine sul campo e sperimentazione laboratoristica.

Nose and paranasal sinus cancers are among the diseases related to exposure to wood dusts. The aim of this study was to evaluate exposure to hardwood dust by workers in small carpentry industries in central Italy (Tuscany, Italy) employing from one to ten workers each, and to investigate pathogenetic mechanisms. The efficacy of ventilation systems was assessed and exposure levels determined. Exposure conditions of hardwood workers were then reproduced in the laboratory and a physical/kinetic model prepared to simulate patterns of air uptake by workers. Various parameters were then measured to investigate possible risk factors that may be related to the onset of the disease. In addition to particle size of wood dust, a factor that requires further investigation is the temperatures reached by wood dust during processing, which may lead to the formation of new harmful molecules.

Occupational risk factors for sinonasal inverted papilloma: a case-control study.

OBJECTIVES: Sinonasal inverted papilloma (IP) is an uncommon benign tumour characterised by frequent recurrence and, in approximately 10% of cases, by neoplastic transformation. IP aetiology is unknown but human papillomavirus is detectable in about one quarter of tumours. As some occupational hazards have been reported to be possible risk factors for IP, the aim of this study was to assess risk for sinonasal IP associated with prior exposure to suspected occupational risk factors for sinonasal malignancies. METHODS: Between 1996 and 2007, data on incident cases were collected from hospitals throughout the Piedmont region of Italy by the regional sinonasal cancer registry. A questionnaire on occupational history, completed by 127 cases and 337 hospital controls, was used to assign previous exposure to a list of 17 occupational hazards. The relationship between IP and cumulative exposure to these hazards was explored using unconditional logistic regression to statistically adjust for age, sex, area of residence, smoking and co-exposures. RESULTS: The risk of IP was significantly increased for ever exposure to welding fumes (OR 2.14) and organic solvents (OR 2.11) after controlling for potential confounders. For organic solvents only, a significant association with continuous cumulative exposure and a significant trend in risk across ordered cumulative exposure categories was found. CONCLUSIONS: The present study revealed a significant association and a significant dose-response relationship between occupational exposure to organic solvents and IP. The lack of a dose-response relationship for welding fumes suggests that the observed association with ever exposure should be interpreted with caution.

Prevalence of occupational hazards in patients with different types of epithelial sinonasal cancers.

BACKGROUND: Occupational exposure to carcinogens contributes greatly to the etiology of sinonasal cancer (SNC), but the role of different risk factors in determining different histological subtypes is disputed. METHODOLOGY: All consecutive surgical epithelial SNC cases (case-series study) underwent a systematic occupational medicine examination to determine previous exposure to a wide range of work-related chemical hazards. RESULTS: We investigated 65 SNC cases including intestinal-type adenocarcinoma [ITAC] squamous-cell carcinoma [SCC], and others. Occupational exposure was recognized for 39 cases. Occupational exposures were sensibly more frequent among ITAC than among SCC or other histotypes. Occupational exposure in ITAC cases was to leather or wood dust only, while among non-ITAC cases, we recognised exposure to formaldehyde, solvents and metal fumes. A high proportion of SNC with occupational exposure originated in the ethmoidal epithelium. CONCLUSION: In our case-series of SNC, a very high frequency of previous occupational exposure to carcinogens was detected, suggesting that occupational hazards may be associated to the aetiopathogenesis, primarily for ITAC, but also for other histotypes. Besides leather or wood, other chemical agents must be recognized as occupational risk factors.

[Leather dusts and cancerogenic effects]. / Polveri di cuoio ed effetti cancerogeni.

Work exposure to carcinogenic chemicals in the shoe industry is still debated owing to continuous technological developments. A possible causal role in sino-nasal cancer development was attributed to the leather dusts basing on epidemiologic studies. Nevertheless, convincing conclusions regarding toxicodinamic-involved processes are actually missing. An hypothesis pointing on tannins toxic action shows insufficient and contrasting data. A cancerogenic risk seems to be attributable for workers engaged in the whole process of shoe industry.

[Leather dust and systematic research on occupational tumors: the national and regional registry TUNS]. / Polveri di cuoio e ricerca sistematica dei tumori professionali: il registro nazionale e regionale TUNS.

The sinonasal cancer (SNC) are a rare tumors characterized by high occupational etiologic fraction. For this reason their incidence and etiology can be actively monitored by a dedicated cancer registry. The National Registry of these tumours is situated at the Italian Institute for Occupational Safety and Prevention (ISPESL) and is based on Regional Operating Centres (ROCs). In Lombardy Region the ROC has been established at the end of 2007 with the purpose to make a systematic surveillance and therefore to support in the most suitable way the scientific research and the prevention actions in the high risk working sectors. The aims of this surveillance are: to estimate the regional incidence of SNC, to define different sources of occupational and environmental exposure both known (wood, leather, nickel, chromium) and unknown. The registry collects all the new incident cases of epithelial SNC occurring in residents in Lombardy Region since 01.01.2008. The regional Registry is managed according to National Guidelines. Until January 2010 we received 596 cases of suspected SNC; only 91 (15%) of these were actually incident cases according to the inclusion criteria of the Registry, and they were preferentially adenocarcinoma and squamous carcinoma. In 2008 the regional age-standardized incidence rate of SNC for males and females, respectively, is 0.8 and 0.5 per 100,000. Occupational or environmental exposure to wood or leather dust is ascertained in over the 50% of cases. The occupational exposure to leather dust was duo to work in shoe factories. Our preliminary findings confirm that occupational exposure to wood and leather dusts are the more relevant risk factors for SNC. The study of occupational sectors and job activity in cases without such exposure could suggest new etiologic hypothesis.

p53 and BCL-2 over-expression inversely correlates with histological differentiation in occupational ethmoidal intestinal-type sinonasal adenocarcinoma.

Despite their histological resemblance to colorectal adenocarcinoma, there is little information on the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinoma (ITACs). The aim of this paper is to evaluate the possible role of TP53 and Bcl-2 gene defects in ITAC by investigating the immunohistochemical expression of TP53 and Bcl-2 gene products in a group of ethmoidal ITACs associated with occupational exposure. A retrospective study on 15 patients with pathological diagnosis of primary ethmoidal ITAC was conducted. Representative formalin-fixed, paraffin wax-embedded block from each case was selected for immunohistochemical studies using the antibodies against p53 and Bcl-2. Clinical-pathological data were also correlated with the staining results. The results of immunohistochemical examination demonstrated that poorly differentiated cases showed a higher percentage of p53 and Bcl-2 expressing cells in comparison to well-differentiated cases. No correlation was found with other clinico-pathological parameters, including T, stage and relapses. The relationship between up-regulation of p53 and Bcl-2 and poorly differentiated ethmoidal adenocarcinoma suggests a role of these genes, in combination with additional genetic events, in the pathogenesis of ITAC.

Sinonasal tumor in 3 dogs after successful topical treatment for frontal sinus aspergillosis.

Three dogs diagnosed with aspergillosis developed sinonasal tumors several months after successful treatment with topical clotrimazole solution. Chronic rhinosinusitis was also detected in all cases prior to diagnosis of sinonasal tumors. The inflammatory response to Aspergillus, clotrimazole treatment, and chronic inflammation after treatment are discussed as possible neoplastic promoting factors.

La OMS considera cancerígeno el formaldehído / Formaldehyde classified as carcinogenic by the WHO

No disponible

[Sino-nasal inverted papillomas and occupational etiology]. / Papillomi invertiti naso-sinusali ed eziologia occupazionale.

The sino-nasal inverted papilloma is a rare benign tumour with certain aggressive features because of frequent relapses and the high probability of malignant degeneration. For these reasons, several studies have been made to evaluate the efficacy of the different courses of treatment, but only afew studies have been carried out to establish the etiology of this tumour, which is still uncertain. Although it is believed that viral infection, chronic inflammation and cigarette smoking can play an important etiological role, it has recently been suggested that occupational risk factors, such as those involved in malignant epithelial sino-nasal cancer (SNC), can also be involved in causing sino-nasal inverted papilloma. A group of 70 patients was examined who have been diagnosed with inverted papilloma from 1991 to 2003; the occupational history, collected via the standardized questionnaire, showed that risk factors like wood and leather dusts, chromium and nickel vapours or fumes and formaldehyde were associated with only 5% of all cases. This proportion is much lower than that established for SNC in several epidemiological studies. Although occupational environmental pollution can be a source of chronic sino-nasal mucosa irritation, on the basis of our results we believe that a causal relationship between exposure to occupational risk factors and inverted papilloma is not likely, differently from the suggestions made in other studies. Consequently, an epidemiological surveillance of inverted papilloma as a "sentinel" tumour, as has been proposed in Italy for SNC, is not considered necessary. Among the possible non-occupational risk factors we observed that 75% of the male patients were smokers and 40% of all patients suffered from chronic sinusitis and sino-nasal polyps. Lastly, among the 70 cases of inverted papilloma, we observed 5 with malignant degeneration.

[A series of cases of sinonasal cancer among shoemakers and tannery workers]. / Analisi di una serie di casi di neoplasie maligne delle fosse nasali e dei seni accessori nel settore conciario e delle calzature.

A series of cases of sinunasal cancer has been observed among shoe-makers (11 cases) and tannery workers (8 cases) in the leather production area in Tuscany in the period 1990-2002. We stress the possible etiologic role of tannins both in leather and in wood industry.

[Health effects of occupational exposure among shoe workers. A review]. / Skutki zdrowotne ekspozycji na czynniki szkodliwe pracowników produkcji i naprawy obuwia.

World-wide epidemiological studies provide evidence that the employment in the shoe production and repair plants is associated with an enhanced risk for cancer (primarily nose and nasal sinuses). According to the majority of authors, it is induced by exposure to leather dust. It is also known that, leather dust particles contain numerous chemicals acquired during the process of leather tanning and finishing (chromium salts, vegetable dye extracts, mineral oils). Some of these compounds exert carcinogenic effect. This paper provides a review of the results of epidemiological studies on health effects of exposure to harmful factors present mainly at the footwear production and repair. These results reveal an enhanced risk for cancer of nose or nasal sinuses induced by leather dust, as well as neoplasms of hematopoietic and lymphatic systems, resulting from exposure to solvents (mostly benzene). Among non-neoplasms, diseases of the musculoskeletal system associated with ergonomic factors, contact dermatics, chronic pulmonary diseases and damage of peripheral nerves in solvent-exposed workers are diagnosed.

Nasal toxicity, carcinogenicity, and olfactory uptake of metals.

Occupational exposures to inhalation of certain metal dusts or aerosols can cause loss of olfactory acuity, atrophy of the nasal mucosa, mucosal ulcers, perforated nasal septum, or sinonasal cancer. Anosmia and hyposmia have been observed in workers exposed to Ni- or Cd-containing dusts in alkaline battery factories, nickel refineries, and cadmium industries. Ulcers of the nasal mucosa and perforated nasal septum have been reported in workers exposed to Cr(VI) in chromate production and chrome plating, or to As(III) in arsenic smelters. Atrophy of the olfactory epithelium has been observed in rodents following inhalation of NiSO4 or alphaNi3S2. Cancers of the nose and nasal sinuses have been reported in workers exposed to Ni compounds in nickel refining, cutlery factories, and alkaline battery manufacture, or to Cr(VI) in chromate production and chrome plating. In animals, several metals (eg, Al, Cd, Co, Hg, Mn, Ni, Zn) have been shown to pass via olfactory receptor neurons from the nasal lumen through the cribriform plate to the olfactory bulb. Some metals (eg, Mn, Ni, Zn) can cross synapses in the olfactory bulb and migrate via secondary olfactory neurons to distant nuclei of the brain. After nasal instillation of a metal-containing solution, transport of the metal via olfactory axons can occur rapidly, within hours or a few days (eg, Mn), or slowly over days or weeks (eg, Ni). The olfactory bulb tends to accumulate certain metals (eg, Al, Bi, Cu, Mn, Zn) with greater avidity than other regions of the brain. The molecular mechanisms responsible for metal translocation in olfactory neurons and deposition in the olfactory bulb are unclear, but complexation by metal-binding molecules such as carnosine (beta-alanyl-L-histidine) may be involved.

K-ras mutations in sinonasal adenocarcinomas in patients occupationally exposed to wood or leather dust.

Of 39 males diagnosed with sinonasal adenocarcinomas over 30 years in the Lund University Hospital catchment area (1.5 million inhabitants), archival tumor tissue was available from 29. Of these, 16 had been exposed to wood dust and three had been exposed to leather dust. The intestinal-type and papillary adenocarcinomas were more common in the exposed patients (P = 0.0002, Fisher's exact test). The tumors from all but one of the 29 sinonasal adenocarcinomas could be analyzed for point mutations at codons 12, 13 and 61 of the K-ras gene. Four mutations were detected in the 28 tumors. The three mutations in the patients exposed to wood and leather dust were all G:C --> A:T transitions, with two at position 2 of codon 12 and one at position 2 of codon 13. The high proportion of G:C --> A:T mutations in this rare tumor may reflect a genotoxic agent in wood and leather dust.

Empirical evaluation of the influence of control selection schemes on relative risk estimation: the Welsh nickel workers study.

OBJECTIVE: To perform an empirical evaluation of the theory that relative incidence rate (RIR) and relative risk (RR) can be directly estimated from case-control studies that have different sampling schemes of controls. METHODS: With data from the South Wales nickel refinery workers (SWNRW) study, a nested case-control study of the relation of nickel exposure to respiratory cancers, was conducted within each of four fixed subcohorts that differed for stability of exposure, incidence rates and RIR. Odds ratios (ORs) and confidence intervals (CIs) were estimated either with all available controls or with randomly sampled subsets of controls. RESULTS: Respiratory cancers were not rare as risk of nasal and lung cancer in workers unexposed to nickel varied from 15% to 26% over the full risk period. The RIR was adequately estimated by the OR when controls were identified concurrently to case occurrence throughout the risk period. The RR was well approximated with the OR when controls were a sample of the study base. CONCLUSIONS: These results add empirical support to the theory that the RIR or the RR can be validly estimated in case-control studies. Overall, this theory is relatively tolerant of large departures from the stability assumptions of exposure and of incidence.