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1.
Hum Mol Genet ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527138

RESUMO

Sexual dimorphism in cancer incidence and outcome is widespread. Understanding the underlying mechanisms is fundamental to improve cancer prevention and clinical management. Sex disparities are particularly striking in kidney cancer: across diverse populations, men consistently show unexplained two-fold increased incidence and worse prognosis. We have characterized genome-wide expression and regulatory networks of 609 renal tumors and 256 non-tumor renal tissues. Normal kidney displayed sex-specific transcriptional signatures, including higher expression of X-linked tumor suppressor genes in women. Sex-dependent genotype-phenotype associations unraveled women-specific immune regulation. Sex differences were markedly expanded in tumors, with male-biased expression of key genes implicated in metabolism, non-malignant diseases with male predominance, and carcinogenesis, including markers of tumor infiltrating leukocytes. Analysis of sex-dependent RCC progression and survival uncovered prognostic markers involved in immune response and oxygen homeostasis. In summary, human kidney tissues display remarkable sexual dimorphism at the molecular level. Sex-specific transcriptional signatures further shape renal cancer, with relevance for clinical management.

2.
Med Pr ; 2020 Dec 02.
Artigo em Polonês | MEDLINE | ID: mdl-33270044

RESUMO

The COVID-19 pandemic, despite the restrictions and preventive measures applied, has rapidly spread and reached Poland. The adaptation to the dynamically changing epidemiological situation requires a prompt implementation of effective preventive measures. The aim of the publication is to provide current knowledge to all persons involved in the preventive care system, i.e., employees, employers and professionals of occupational medicine, about the epidemiological situation related to SARS­CoV- 2, as well as recommendations and possible solutions. In order to analyze these issues, a review of literature was conducted based on medical research databases: PubMed, SCOPUS, and the Web of Science Core Collection. The literature was supplemented with studies found on websites of the Ministry of Health and the World Health Organization. Data on the cases of and deaths due to COVID-19 come from reports provided by the Ministry of Health, data published on the websites of the European Center for Disease Prevention and Control, and ourworldindata.org. By the time of submitting the publication, 34 154 cases and 1444 deaths due to coronavirus had been recorded in Poland. Data from published studies suggest that the virus is mainly transmitted via droplets or through contact with contaminated objects and surfaces. Therefore, in the absence of an effective vaccine, preventive actions are based mainly on strategies that minimize the risk of pathogen transmission. In addition to discussing the current epidemiological situation, diagnostic procedures, risk groups and COVID-19 characteristics, the paper presents recommendations and proposed solutions for employers and employees regarding the prevention of SARS­CoV- 2, along with currently applicable laws and recommendations on employee prophylactic examinations during the pandemic. Subsequently, COVID-19 was discussed in the aspect of an occupational disease and other health threats related to the pandemics. The epidemiological situation regarding coronavirus indicates the need to take immediate and effective actions to minimize infection transmission among employees, and to develop procedures for a quick and effective ability to locate the COVID-19 outbreaks in workplaces. Med Pr. 2021;72(1).

3.
Occup Environ Med ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115922

RESUMO

OBJECTIVES: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project. METHODS: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens. RESULTS: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0). CONCLUSIONS: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.

4.
Med Pr ; 71(5): 595-601, 2020 Sep 24.
Artigo em Polonês | MEDLINE | ID: mdl-32667289

RESUMO

BACKGROUND: Despite the ban on the production of asbestos-containing materials, introduced in Poland over 20 years ago, new cases of asbestos-related diseases are still being recorded. Systematic control of respiratory function in people exposed to asbestos dust is, therefore, extremely important due to the biological properties of this mineral. MATERIAL AND METHODS: The Amiantus preventive medical examination program was undertaken in 2000 to implement the legal rights of former employees of asbestos processing plants for this type of examinations. People who have ever been employed in such factories have been authorized to use preventive medical examinations for the rest of their lives. The research is continuous, spread over time and focused, in particular, on the assessment of the respiratory system. RESULTS: Since the beginning of the program, throughout 20 years of its implementation, 8329 people have been examined, including 5199 (62.4%) men for whom a total of 34 454 medical examinations have been carried out. During the program period, the percentage of diagnosed pathologies increased from 8% in 2000 to 25% in 2019. Overall, 2078 asbestos-related diseases were diagnosed among former employees of asbestos processing plants under the Amiantus Program, which accounted for 25% of this group. Among all diseases caused by exposure to asbestos, the most common were: asbestosis (1880 cases - 90.5%), lung cancer (121 cases - 5.8%) and pleural mesothelioma (77 cases - 3.7%). Diseases of pleura in the form of plaques and diffuse pleural thickening were diagnosed in 40% of the examined patients, while radiological pulmonary shadows affected over 65% of former employees of asbestos processing plants. CONCLUSIONS: The Amiantus Program, thanks to the long observation period, enabled monitoring the health of former employees exposed to asbestos, and created a unique opportunity to carry out epidemiological analyzes. These studies allowed the authors to expand their knowledge of the natural history of asbestos-related diseases. Med Pr. 2020;71(5):595-601.

5.
Am J Respir Crit Care Med ; 202(3): 412-421, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330394

RESUMO

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Dióxido de Silício , Silicose/epidemiologia , Adulto , Idoso , Canadá/epidemiologia , Fumar Cigarros , Europa (Continente)/epidemiologia , Feminino , Humanos , Exposição por Inalação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
6.
Am J Respir Crit Care Med ; 202(3): 402-411, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330395

RESUMO

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 µg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Fumar Cigarros/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Emissões de Veículos , Adulto , Idoso , Canadá/epidemiologia , Carbono , Europa (Continente)/epidemiologia , Feminino , Humanos , Exposição por Inalação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores Sexuais
8.
Med Pr ; 70(6): 723-731, 2019 Dec 03.
Artigo em Polonês | MEDLINE | ID: mdl-31682242

RESUMO

BACKGROUND: Despite the fact that asbestos is no longer used in production in Poland, there are still new cases of asbestos-related diseases among workers previously exposed to asbestos dust. This situation is related to the specificity of the biological activity of this mineral; the health consequences of asbestos can manifest not only during the exposure but also many years after exposure cessation. The aim of the analysis was to assess the occurrence of occupational diseases among people exposed to asbestos dust, who were examined under the Amiantus program. MATERIAL AND METHODS: The research material consisted of the program cards filled by the doctors conducting the examinations as well as radiological images stored on the International Labour Organization form. The analysis covered 8049 people, including 37% of women surveyed in the years 2000-2017. RESULTS: In the group of former employees of asbestos processing plants, the occupational disease was diagnosed in 1993 people (25%), including 584 women (19%). The most common was asbestosis (76% of occupational diseases) and pleural disease (17%). Malignant neoplasms accounted for 7% of all cases in this group. The analysis showed an increase in the incidence of respiratory system diseases along with the age of the surveyed persons, their seniority at asbestos processing plants and an increase in cumulative exposure. The chest radiographs revealed radiological changes among 75% of the examined cases, whereas the changes entitling to diagnose asbestosis, according to the criteria applicable in Poland, occurred in 23% of the workers. The adoption of international criteria would increase the incidence of asbestosis as an occupational disease by 19% in the study group. CONCLUSIONS: The increase in the percentage of people with a diagnosed occupational disease provides evidence for the worsening health status of the former workers as well as a good detection of asbestos-related diseases among employees exposed to asbestos dust in the past. The results of the analysis indicate the need for undertaking a discussion in Poland on the implementation of international criteria for the diagnosis of asbestosis. Med Pr. 2019;70(6):723-31.


Assuntos
Asbestos/efeitos adversos , Asbestose/epidemiologia , Neoplasias Pulmonares/induzido quimicamente , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Vigilância da População
9.
Cancer Epidemiol ; 63: 101615, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31586822

RESUMO

BACKGROUND: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk. METHODS: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models. RESULTS: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR<10 years vs. ≥30 years: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR<10 years vs. ≥30 years: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed. CONCLUSIONS: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Tabaco/efeitos adversos , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
Eur J Hum Genet ; 27(10): 1589-1598, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31231134

RESUMO

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.


Assuntos
Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Renais/epidemiologia , Neoplasias Renais/genética , Biologia Computacional , Feminino , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Fatores Sexuais
11.
Oral Oncol ; 94: 47-57, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31178212

RESUMO

OBJECTIVES: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.


Assuntos
Fumar Cigarros/efeitos adversos , Neoplasias de Cabeça e Pescoço/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
12.
Am J Psychiatry ; 176(8): 651-660, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31164008

RESUMO

OBJECTIVE: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium. METHODS: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders. RESULTS: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%). CONCLUSIONS: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.


Assuntos
Transtorno Bipolar/genética , Transtorno Depressivo Maior/genética , Herança Multifatorial/genética , Esquizofrenia/genética , Tentativa de Suicídio , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Transtorno Depressivo Maior/psicologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Fatores de Risco
13.
Oncotarget ; 10(19): 1760-1774, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30956756

RESUMO

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.

14.
Med Pr ; 69(6): 643-650, 2018 12 18.
Artigo em Polonês | MEDLINE | ID: mdl-30444221

RESUMO

BACKGROUND: The aim of the work is to present the epidemiological situation in the field of occupational diseases in Poland in 2016. MATERIAL AND METHODS: The cases of occupational diseases identified in accordance with the applicable case law system in Poland and reported to the Central Register of Occupational Diseases in 2016 were analyzed. The analysis includes nosologic units, their causative factors as well as gender and age of patients. Absolute numbers and incidence rates per 100 000 employees were presented. RESULTS: In 2016, 2119 cases of occupational diseases were recorded in Poland, i.e. 14.3 cases per 100 000 employed persons. The incidence rate was mainly caused by pneumoconioses (28.5%), infectious or parasitic diseases (27.2%), chronic voice disorders (9.7%), chronic diseases of the peripheral nervous system (8.6%) and hearing loss (6.3%). The highest incidence was recorded in the mining and quarrying (329.7 cases), agriculture and forestry (23.8 cases), manufacturing (20 cases) and education (17.9 cases) and healthcare and social work activities (17.7 cases). CONCLUSIONS: In comparison with 2015, there was an increase in the number of cases of occupational diseases by 1.2%, which was influenced mainly by a larger (by 181 cases) number of pneumoconiosis. The epidemiological situation resulting from occupational diseases in our country, although it covers all identified cases, should be assessed with caution because the suspicion arises underestimation of certain diseases, especially cancer. Med Pr 2018;69(6):643-650.


Assuntos
Doenças Profissionais/epidemiologia , Sistema de Registros , Feminino , Perda Auditiva/epidemiologia , Humanos , Incidência , Infecções/epidemiologia , Masculino , Pneumoconiose/epidemiologia , Polônia/epidemiologia , Distúrbios da Voz/epidemiologia
15.
Med Pr ; 69(5): 531-538, 2018 10 30.
Artigo em Polonês | MEDLINE | ID: mdl-30245518

RESUMO

BACKGROUND: The aim of the paper is to present statistical data on the occurrence of occupational diseases among healthcare and social workers in Poland in 2009-2016. MATERIAL AND METHODS: All cards certifying that a case of occupational disease had been diagnosed in a patient belonging to this occupational group, received by the Central Register of Occupational Diseases, served as the basis of the study. Data is presented in absolute numbers and incidence rates. In the analysis, disease categories, voivodships and occupations were taken into account. RESULTS: In 2009-2016, as many as 1462 cases of occupational diseases were diagnosed for healthcare workers. In 2016, the number of cases was 42.6% lower than in 2009. Mean annual incidence rate in these years was 26.3 cases per 100 thousand workers. The most frequent were: infectious and parasitic diseases (64.8% of cases), peripheral nervous system diseases (9.6%), dermal diseases (8.9%), locomotor (8.3%), and chronic vocal organ disorders (3.2%). Among infectious or parasitic diseases, the most cases were viral hepatitis (56%) and tuberculosis (39%). Almost every second case of occupational disease in healthcare workers was detected in the nurses (47.8%). CONCLUSIONS: The incidence of occupational diseases in total and in the most frequent categories continued to decrease. One of the reasons for the decline is the improvement of working conditions resulting from the application of more modern instruments and apparatus as well as greater knowledge of the risks and the use of appropriate procedures. Med Pr 2018;69(5).


Assuntos
Pessoal de Saúde , Doenças Profissionais/epidemiologia , Assistentes Sociais , Adulto , Humanos , Incidência , Pessoa de Meia-Idade , Polônia/epidemiologia , Sistema de Registros
16.
Nat Commun ; 9(1): 3927, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30254314

RESUMO

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.


Assuntos
Mapeamento Cromossômico , Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Complexo Principal de Histocompatibilidade/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Antígenos HLA/genética , Humanos , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Peptídeos/genética , Polimorfismo de Nucleotídeo Único
17.
J Thorac Oncol ; 13(10): 1483-1495, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29981437

RESUMO

BACKGROUND: Genome-wide association studies are widely used to map genomic regions contributing to lung cancer (LC) susceptibility, but they typically do not identify the precise disease-causing genes/variants. To unveil the inherited genetic variants that cause LC, we performed focused exome-sequencing analyses on genes located in 121 genome-wide association study-identified loci previously implicated in the risk of LC, chronic obstructive pulmonary disease, pulmonary function level, and smoking behavior. METHODS: Germline DNA from 260 case patients with LC and 318 controls were sequenced by utilizing VCRome 2.1 exome capture. Filtering was based on enrichment of rare and potential deleterious variants in cases (risk alleles) or controls (protective alleles). Allelic association analyses of single-variant and gene-based burden tests of multiple variants were performed. Promising candidates were tested in two independent validation studies with a total of 1773 case patients and 1123 controls. RESULTS: We identified 48 rare variants with deleterious effects in the discovery analysis and validated 12 of the 43 candidates that were covered in the validation platforms. The top validated candidates included one well-established truncating variant, namely, BRCA2, DNA repair associated gene (BRCA2) K3326X (OR = 2.36, 95% confidence interval [CI]: 1.38-3.99), and three newly identified variations, namely, lymphotoxin beta gene (LTB) p.Leu87Phe (OR = 7.52, 95% CI: 1.01-16.56), prolyl 3-hydroxylase 2 gene (P3H2) p.Gln185His (OR = 5.39, 95% CI: 0.75-15.43), and dishevelled associated activator of morphogenesis 2 gene (DAAM2) p.Asp762Gly (OR = 0.25, 95% CI: 0.10-0.79). Burden tests revealed strong associations between zinc finger protein 93 gene (ZNF93), DAAM2, bromodomain containing 9 gene (BRD9), and the gene LTB and LC susceptibility. CONCLUSION: Our results extend the catalogue of regions associated with LC and highlight the importance of germline rare coding variants in LC susceptibility.


Assuntos
Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
18.
EBioMedicine ; 32: 93-101, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29859855

RESUMO

Recent technological advancements have permitted high-throughput measurement of the human genome, epigenome, metabolome, transcriptome, and proteome at the population level. We hypothesized that subsets of genes identified from omic studies might have closely related biological functions and thus might interact directly at the network level. Therefore, we conducted an integrative analysis of multi-omic datasets of non-small cell lung cancer (NSCLC) to search for association patterns beyond the genome and transcriptome. A large, complex, and robust gene network containing well-known lung cancer-related genes, including EGFR and TERT, was identified from combined gene lists for lung adenocarcinoma. Members of the hypoxia-inducible factor (HIF) gene family were at the center of this network. Subsequent sequencing of network hub genes within a subset of samples from the Transdisciplinary Research in Cancer of the Lung-International Lung Cancer Consortium (TRICL-ILCCO) consortium revealed a SNP (rs12614710) in EPAS1 associated with NSCLC that reached genome-wide significance (OR = 1.50; 95% CI: 1.31-1.72; p = 7.75 × 10-9). Using imputed data, we found that this SNP remained significant in the entire TRICL-ILCCO consortium (p = .03). Additional functional studies are warranted to better understand interrelationships among genetic polymorphisms, DNA methylation status, and EPAS1 expression.


Assuntos
Adenocarcinoma/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Pulmonares/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Metilação de DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
19.
Carcinogenesis ; 39(3): 336-346, 2018 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-29059373

RESUMO

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Fumar/efeitos adversos , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu , Interação Gene-Ambiente , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
20.
PLoS One ; 12(6): e0177875, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28594918

RESUMO

BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. CONCLUSIONS: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.


Assuntos
Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Análise da Randomização Mendeliana , Obesidade/complicações , Índice de Massa Corporal , Jejum , Humanos , Insulina/sangue , Resistência à Insulina , Funções Verossimilhança , Lipídeos/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Obesidade/sangue , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de Risco
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