Integrative genomics analysis of nasal intestinal-type adenocarcinomas demonstrates the major role of CACNA1C and paves the way for a simple diagnostic tool in male woodworkers

Abstract Background Nasal intestinal-type adenocarcinomas (ITAC) are strongly related to chronic wood dust exposure: The intestinal phenotype relies on CDX2 overexpression but underlying molecular mechanisms remain unknown. Our objectives were to investigate transcriptomic and methylation differences between healthy non-exposed and tumor olfactory cleft mucosae and to compare transcriptomic profiles between non-exposed, wood dust-exposed and ITAC mucosa cells. Methods We conducted a prospective monocentric study (NCT0281823) including 16 woodworkers with ITAC, 16 healthy exposed woodworkers and 13 healthy, non-exposed, controls. We compared tumor samples with healthy non-exposed samples, both in transcriptome and in methylome analyses. We also investigated wood dust-induced transcriptome modifications of exposed (without tumor) male woodworkers’ samples and of contralateral sides of woodworkers with tumors. We conducted in parallel transcriptome and methylome analysis, and then, the transcriptome analysis was focused on the genes highlighted in methylome analysis. We replicated our results on dataset GSE17433. Results Several clusters of genes enabled the distinction between healthy and ITAC samples. Transcriptomic and IHC analysis confirmed a constant overexpression of CDX2 in ITAC samples, without any specific DNA methylation profile regarding the CDX2 locus. ITAC woodworkers also exhibited a specific transcriptomic profile in their contralateral (non-tumor) olfactory cleft, different from that of other exposed woodworkers, suggesting that they had a different exposure or a different susceptibility. Two top-loci (CACNA1C/CACNA1C-AS1 and SLC26A10) were identified with a hemimethylated profile, but only CACNA1C appeared to be overexpressed both in transcriptomic analysis and in immunohistochemistry. Conclusions Several clusters of genes enable the distinction between healthy mucosa and ITAC samples even in contralateral nasal fossa thus paving the way for a simple diagnostic tool for ITAC in male woodworkers. CACNA1C might be considered as a master gene of ITAC and should be further investigated. Trial registration: NIH ClinicalTrials, NCT0281823, registered May 23d 2016, https://www.clinicaltrials.gov/NCT0281823.

Download Full-text

Occurrence of Sinonasal Intestinal-Type Adenocarcinoma and Non-Intestinal-Type Adenocarcinoma in Two Countries with Different Patterns of Wood Dust Exposure

Cancers ◽

10.3390/cancers13205245 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5245

Author(s):

Ilmo Leivo ◽

Reetta Holmila ◽

Danièle Luce ◽

Torben Steiniche ◽

Michael Dictor ◽

...

Keyword(s):

Systematic Study ◽

Diagnostic Workup ◽

Intestinal Type ◽

Dust Exposure ◽

Wood Dust ◽

Systematic Comparison ◽

Sinonasal Adenocarcinoma ◽

Intestinal Type Adenocarcinoma ◽

Tumor Types

Sinonasal intestinal-type adenocarcinoma is strongly associated with hardwood dust exposure. Non-intestinal-type adenocarcinoma is a rarer and less well-known subtype considered not to be related with wood dust exposure. We determined the relative numbers of these two tumor types in 56 sinonasal adenocarcinoma patients in France and Finland, relating them with carefully assessed wood dust exposure histories. Diagnostic workup including immunohistochemistry for the intestinal markers CDX2 and CK20 indicated that the proportions of the two tumors differed significantly between France and Finland. In Finnish samples non-intestinal adenocarcinomas were more common than intestinal-type adenocarcinomas (12 non-intestinal vs. nine intestinal), while in the French samples the reverse was true (six non-intestinal vs. 29 intestinal). Such remarkably dissimilar occurrence of these tumors in France and Finland presumably reflects different pathogenetic circumstances in the two countries, and perhaps their different patterns of wood dust exposure. In France the main source of wood dust is from hardwoods. In Finland it is derived from softwoods. This is the first systematic comparison of the occurrence of intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma in two countries with different wood usage. It appears to be the first systematic study on differences in wood dust exposure between intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma.

Download Full-text

Occupational exposures and odds of gastric cancer: a StoP project consortium pooled analysis

International Journal of Epidemiology ◽

10.1093/ije/dyz263 ◽

2020 ◽

Vol 49 (2) ◽

pp. 422-434 ◽

Cited By ~ 1

Author(s):

Shailja C Shah ◽

Paolo Boffetta ◽

Kenneth C Johnson ◽

Jinfu Hu ◽

Domenico Palli ◽

...

Keyword(s):

Gastric Cancer ◽

Odds Ratio ◽

Occupational Exposures ◽

Pooled Analysis ◽

Intestinal Type ◽

Dust Exposure ◽

Wood Dust ◽

Diffuse Type ◽

Cancer Pathogenesis ◽

The Impact

Abstract Background Gastric cancer pathogenesis represents a complex interaction of host genetic determinants, microbial virulence factors and environmental exposures. Our primary aim was to determine the association between occupations/occupational exposures and odds of gastric cancer. Methods We conducted a pooled-analysis of individual-level data harmonized from 11 studies in the Stomach cancer Pooling Project. Multivariable logistic regression was used to estimate the odds ratio (OR) of gastric cancer adjusted for relevant confounders. Results A total of 5279 gastric cancer cases and 12 297 controls were analysed. There were higher odds of gastric cancer among labour-related occupations, including: agricultural and animal husbandry workers [odds ratio (OR) 1.33, 95% confidence interval (CI): 1.06–1.68]; miners, quarrymen, well-drillers and related workers (OR 1.70, 95% CI: 1.01–2.88); blacksmiths, toolmakers and machine-tool operators (OR 1.41, 95% CI: 1.05–1.89); bricklayers, carpenters and construction workers (OR 1.30, 95% CI: 1.06–1.60); and stationary engine and related equipment operators (OR 6.53, 95% CI: 1.41–30.19). The ORs for wood-dust exposure were 1.51 (95% CI: 1.01–2.26) for intestinal-type and 2.52 (95% CI: 1.46–4.33) for diffuse-type gastric cancer. Corresponding values for aromatic amine exposure were 1.83 (95% CI: 1.09–3.06) and 2.92 (95% CI: 1.36–6.26). Exposure to coal derivatives, pesticides/herbicides, chromium, radiation and magnetic fields were associated with higher odds of diffuse-type, but not intestinal-type gastric cancer. Conclusions Based on a large pooled analysis, we identified several occupations and related exposures that are associated with elevated odds of gastric cancer. These findings have potential implications for risk attenuation and could be used to direct investigations evaluating the impact of targeted gastric cancer prevention/early detection programmes based on occupation.

Download Full-text

Ethmoid Carcinoma Link to Wood Dust Exposure Found

Skin & Allergy News ◽

10.1016/s0037-6337(08)70748-4 ◽

2008 ◽

Vol 39 (10) ◽

pp. 24

Author(s):

ROBERT FINN

Keyword(s):

Dust Exposure ◽

Wood Dust

Download Full-text

A Study on Effects of Wood Dust Exposure on Pulmonary Functions in Carpenters And Non Carpenters of Urban Ahmedabad

International Journal of Scientific Research ◽

10.15373/22778179/feb2014/125 ◽

2012 ◽

Vol 3 (2) ◽

pp. 383-385

Author(s):

DR KETAN PATEL ◽

◽

DR VIJAY GOPLANI ◽

DR PARESH PRAJAPATI ◽

DR PIYUSH MAKWANA

Keyword(s):

Dust Exposure ◽

Wood Dust ◽

Pulmonary Functions

Download Full-text

Respiratory Tract Problems among Wood Furniture Manufacturing Factory Workers in the Northeast of Thailand

Kathmandu University Medical Journal ◽

10.3126/kumj.v13i2.16784 ◽

2017 ◽

Vol 13 (2) ◽

pp. 125-129 ◽

Cited By ~ 3

Author(s):

I. Soongkhang ◽

W. Laohasiriwong

Keyword(s):

Respiratory Symptoms ◽

Dust Exposure ◽

Wood Dust ◽

P Value ◽

Factory Workers ◽

Cross Sectional ◽

Furniture Manufacturing ◽

Reduce Lung Function ◽

Medium Level ◽

Wood Furniture

Background Wood furniture manufacturing factory workers are at high risk of exposure to wood dust in wood working processes. Wood dust exposure could cause respiratory symptoms, such as reduce lung function, chronic bronchitis, and asthma. The Northeast region of Thailand has many wood furniture manufacturing factories. However, limited studies were carried out to explore the effect of wood dust exposure on workers.Objective This study aimed to assess the respiratory symptoms and determine factors associated with these symptoms among wood furniture manufacturing factory workers.Method This cross-sectional analytical research used a multistage random sampling to select 511 workers from three provinces in the Northeast of Thailand. The data was collected using a structured questionnaire interview. The content validity of questionnaire was tested by 3 experts and had a Cronbach’s alpha coefficient of 0.82. Data were analyzed using descriptive statistics and multiple logistic regressions.Result The result indicated that 29.94% of these workers had respiratory symptoms, including coughing(18.79%), nasal secretion (15.66%), and stuffy nose (15.07%). Factors that were significantly associated with respiratory symptoms (p–value<0.05) were (a) not always wearing mask (adjusted OR=2.26;95% CI=1.37-3.72), (b) low to medium level of knowledge on dust prevention (adjusted OR=1.83;95% CI=1.23- 2.73) and (c) contacted softwood dust (adjusted OR=1.97;95% CI= 1.06-3.64).Conclusion About 30% of wood furniture manufacturing factory workers had respiratory symptoms with related to both personal preventive behaviors and their working environments. Therefore, the raising awareness for using personal protective equipment during work will help them to prevent from various respiratory track problems.

Download Full-text

Worker Characteristics and Dust Exposure to Pulmonary Function Status in Jumping Saw Division Of Wood Industry At Banyuwangi: An Association Study

JURNAL KESEHATAN LINGKUNGAN ◽

10.20473/jkl.v11i2.2019.99-107 ◽

2019 ◽

Vol 11 (2) ◽

pp. 99

Author(s):

Desy Tri Wulansari

Keyword(s):

Pulmonary Function ◽

Smoking Habit ◽

Dust Exposure ◽

Wood Dust ◽

Wood Industry ◽

Chi Square ◽

Cross Sectional ◽

Lung Physiology ◽

Dust Level ◽

Worker Characteristics

Wood dust in the air will bring serious health problems if it is prolonged. Wood Dust has effect for health due to its effect on , pulmonary function via respiratory system entrance. The aim of this study was to analyze the association of worker characteristics and dust exposure to pulmonary function status in jumping saw division workers in wood industry Sempu, Banyuwangi. The research was observasional with cross sectional desain. Research data was obtained by giving questionnaire to respondent, measurement of dust level by using HVAS and lung physiology examination using spirometry tool. The sampel in this research was 7 workers in the part of jumping saw and 6 worker in the part of office. Data were analyzed with chi square statistical test to analyzing the association and statistical t-test to analyzing difference pulmonary function status between to 2 groups. The result showed that dust level in the exposure groups of jumping saw workers was 19,90 mg/m3 and non-exposure group (office) was 0,089 mg/m3, suitable with Permenakertrans No. 13/MEN/X/2011 is 5 mg/m3. Results of lung function measurement showed that normal 15,38% and impairment 84,62%. It is concluded that no associoation between age, length of employment, smoking habit, respiratory ptotective equipment usage habit, respiratory diseases history and dust exposure to pulmonary function status, except association between nutrion status with pulmonary function status. The company should monitor the levels of wood dust, to ensure that it does not exceed the NAB and regular lung physiological health checks.

Download Full-text

Recurrent DNA copy number alterations in intestinal-type sinonasal adenocarcinoma

Rhinology Journal ◽

10.4193/rhino15.382 ◽

2016 ◽

Vol 54 (3) ◽

pp. 278-286

Author(s):

J. Perez-Escuredo ◽

A. Lopez-Hernandez ◽

M. Costales ◽

F. Lopez ◽

S.P. Ares ◽

...

Keyword(s):

Clinical Outcome ◽

Copy Number ◽

Genetic Alterations ◽

Intestinal Type ◽

Dust Exposure ◽

Copy Number Alterations ◽

A Genome ◽

Sinonasal Adenocarcinoma ◽

Gains And Losses ◽

Microarray Cgh

Background: Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumour related to occupational wood dust exposure. Few studies have described recurrent genetic changes on a genome-wide scale. The aim of this study was to obtain a high resolution map of recurrent genetic alterations in ITAC. Material and methods: Copy number alterations were evaluated by microarray CGH and MLPA in 37 primary tumours. The results were correlated with pathological characteristics and clinical outcome. Results: Microarray CGH identified the following recurrent aberrations, in descending order: gains at 5p15 (22 cases, 60%), 8q24 (21 cases, 57%), 20q13 (20 cases, 54%), 20q11, and 8q21 (19 cases, 51%), 20p13, and 7p11 (16 cases, 43%), and losses at 5q11-qter, 8p12-pter, and 18q12-23 (15 cases, 40%), and 17p13, and 19p13 (13 cases, 35%). MLPA analysis confirmed this global pattern of gains and losses. Chromosomal loss at 4q32-ter and gains at 1q22, 6p22 and 3q29, as well as deletion of TIMP2 and CRK correlated with unfavourable clinical outcome. Conclusion: ITACs have a unique pattern of chromosomal abnormalities. The four different histological subtypes of ITAC appeared genetically similar. Four chromosomal gains and losses and two specific genes showed prognostic value and may be involved in tumour progression.

Download Full-text

Ermittlung der Staubemissionen an Holz-Bearbeitungsmaschinen/Determining the dust emission of woodworking machines for risk assessment

wt Werkstattstechnik online ◽

10.37544/1436-4980-2020-01-02-66 ◽

2020 ◽

Vol 110 (01-02) ◽

pp. 64-69

Author(s):

Hans-Christian Möhring ◽

Thomas Stehle ◽

Matthias Schneider

Keyword(s):

Collection Efficiency ◽

Dust Emission ◽

Gravimetric Method ◽

Measuring Method ◽

Dust Exposure ◽

Wood Dust ◽

Suction System ◽

Process Step ◽

Machine Manufacturer ◽

Detailed Assessment

Im Beitrag werden zwei Verfahren zur Ermittlung der Staubemission an Werkzeugmaschinen vorgestellt. Es werden das „gravimetrische Verfahren“ und die „Ermittlung des Erfassungsgrades“ beschrieben und gegenübergestellt. Das gravimetrische Verfahren zur Ermittlung des luftgetragenen Holzstaubs ist Stand der Technik zur Beurteilung der Staubemission von Holzbearbeitungsmaschinen. Dieses aufwendige Messverfahren mit Staub-Probenentnahmegeräten erlaubt eine Aussage über den Emissionsgrad der untersuchten Maschine. Dagegen quantifiziert die Ermittlung des Erfassungsgrades einer Bearbeitungsmaschine die Effektivität des Absaugsystems bei der Erfassung von Spänen und Stäuben. Ein Vergleich von Gravimetrie und Erfassungsgrad soll eine detaillierte Aussage zu den emittierten Späne- und Staubmengen von Bearbeitungsmaschinen für die Holz- und Holzwerkstoffbearbeitung liefern. Beim Messverfahren Ermittlung des Erfassungsgrades wird davon ausgegangen, dass Späne- und Staubfraktionen ähnlich gut erfasst werden können. Die genaue Zusammensetzung der erfassten und nichterfassten Materialanteile sowie der Partikelgrößen sind derzeit noch Gegenstand der Untersuchungen. Unbenommen davon müssen im Betrieb die nichterfassten Anteile aufwendig vom Benutzer in einem nachgelagerten Prozessschritt aufgesaugt werden. Es wird ausdrücklich darauf hingewiesen, dass die Untersuchung des Emissions- oder Erfassungsgrades einer Maschine nur eine qualitative Aussage zur Staubbelastung in der Umgebung einer Maschine erlaubt. Die Einwirkung beziehungsweise Exposition von Mitarbeitern hängt von Umgebungsbedingungen wie zum Beispiel Raumgröße, Luftwechsel, Sauberkeit, Leistung der Absauganlage, Beeinflussung durch Nachbararbeitsplätze (Bystanderexposition) und nicht zuletzt vom Handling des Bedieners ab. Diese Faktoren werden im Allgemeinen nicht von der Maschine beziehungsweise dem Maschinenhersteller beeinflusst.   This paper presents two methods for determining the dust emission of machine tools. The gravimetric method and the determination of the degree of collection efficiency are described and compared. compared. The gravimetric method for establishing airborne wood dust is state of the art for assessing the dust emission of woodworking machines. This complicated measuring method with dust sampling devices makes it possible to assess the emissivity of the examined machine. In contrast, establishing the degree of collection efficiency for a machining centre quantifies how efficient the suction system collects chips and dust. By comparing gravimetric analyses and the degree of collection efficiency, it is possible to provide a detailed assessment about the amount of chips and dust emitted by machining centres in the machining of wood and wood-based products. The measuring method for establishing the degree of collection efficiency assumes that chip and dust fractions can be collected similarly well. The exact composition of the collected and uncollected material fractions as well as the particle sizes still have to be examined yet. Irrespective of that, the uncollected particles have to be removed during operation in a subsequent, complicated process step by the user. It has to be emphasized particularly that by analysing the emissivity or the degree of collection efficiency of a machine it is only possible to qualitatively assess the dust exposure in the surroundings of the machine. The influence or exposure of workers depends on environmental conditions, such as e.g. room size, air change, cleanness, the efficiency of the suction system, the influence by adjacent machines (bystander exposure) and last but not least the handling of the operator. In general, these factors are not influenced by the machine or rather the machine manufacturer.

Download Full-text