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Respirable Crystalline Silica (RCS) is a hazardous substance with known effects that can be well correlated with exposure levels that still persist in many traditional sectors, such as construction or stone processing. In the past decade, exposure scenarios for RCS have been found in the sector of artificial stone processing. The aim of this study is to evaluate the levels of RCS in facilities specialized in the production of artificial stone countertops and other accessories for the furnishing of kitchens, bathrooms, and offices after the introduction of some preventive technical measures such as wet processing or local exhaust ventilation systems. The study involved 51 subjects in four facilities. Personal silica exposure assessment was carried out using GS3 cyclones positioned in the breathing zone during the work shift. Quantitative determination of silica was carried out by X-ray diffraction analysis. Respirable dust levels were in the range 0.046-1.154 mg/m3 with RCS levels within the range

Background Recent studies have shown that nurses have been more affected by the COVID-19 pandemic than any other group of hospital workers in terms of anxiety, depression, and burnout. Several clinical studies had previously demonstrated the effectiveness of mindfulness and compassion interventions in reducing burnout and emotional distress amongst healthcare professionals. Methods and analysis A parallel-group randomized controlled trial will assess the feasibility, acceptability, and efficacy of a mindfulness and compassion-focused programme on frontline nurses who had been working during the COVID-19 pandemic. Seventy-two participants will be recruited from Verona University Hospital Trust (Veneto Region, north-east Italy) and will be divided equally into an intervention group and a control group. Primary outcome will be assessed using the Emotional Exhaustion subscale of the Maslach Burnout Inventory General Survey (MBI-GS). Secondary outcomes will be measured by the Cynicism and Professional Efficacy subscales of the MBI-GS, the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder (GAD-7), the Insomnia Severity Index (ISI), the Impact of Stressful Events (IES-R), the Perceived Stress Scale (PSS), the Five Facet Mindfulness Questionnaire (FFMQ), and the Forms of Self-Criticising/attacking and Self-Reassuring Scale (FSCRS). Discussion The study aims to fill a gap in the literature and present a scientifically validated intervention for those healthcare professionals most exposed to the stressful conditions of working during the COVID-19 pandemic. Trial registration ClinicalTrials.gov; Identifier: NCT05308537

The use of digital devices affects eye health; this can influence the performance of workers. To assess this impact, validated patient-reported outcome questionnaires are needed. The purpose of this study was to validate the psychometric properties of the Italian version of the Computer Vision Syndrome Questionnaire (CVS-Q©) using Rasch analysis. Two hundred and forty-one Italian workers completed an ad hoc questionnaire on anamnesis and exposure to digital devices, and the Italian version of the CVS-Q©. Subsequently, a battery involving three clinical ocular surface and tear tests was performed. The reliability and validity of the scale was assessed using the Andrich Rating Scale Model, and the prevalence of computer vision syndrome (CVS) was calculated. A good fit of both items and persons to the predictions of the Rasch model was observed, with acceptable reliability, unidimensionality, and no or minimal severe differences as a function of gender or age; moreover, good test–retest repeatability, adequate values of sensitivity, reliability, and area under the curve, and adequate construct validity based on clinical tests were obtained. Workers with a questionnaire score ≥ 7 were found to present with CVS. The prevalence of CVS was 76.6%. The CVS-Q IT© is a valid and reliable scale to assess CVS in Italian workers who use digital devices.

At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case–control and one nested case–cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.

Over the last few decades, the migratory phenomenon, supported by social, economic, and political aspects, has become progressively intensified and structured, increasing its relevance as a topic of interest for researchers of various disciplines and, among these, occupational health and safety exerts a prominent role [...]

Background: We described a SARS-CoV-2 thrice-infected case series in health workers (HW) to evaluate patient and virus variants and lineages and collect information on variables associated with multiple infections. Methods: A retrospective analysis of clinical and laboratory characteristics of SARS-CoV-2 thrice-infected individuals was carried out in Verona University Hospital, concurrent with the ORCHESTRA project. Variant analysis was conducted on a subset of available specimens. Results: Twelve HW out of 7368 were thrice infected (0.16%). Symptomatic infections were reported in 63.6%, 54.5% and 72.7% of the first, second and third infections, respectively. Nine subjects were fully vaccinated at the time of the third infection, and five had an additional booster dose. The mean time to second infection was 349.6 days (95% CI, 138–443); the mean interval between the second and third infection was 223.5 days (95% CI, 108–530) (p = 0.032). In three cases, the second and third infections were caused by the Omicron variant, but different lineages were detected when the second vs third infections were sequenced. Conclusions: This case series confirms evidence of multiple reinfections with SARS-CoV-2, even from the same variant, in vaccinated HW. These results reinforce the need for continued infection-specific prevention measures in previously infected and reinfected HW.

This study aimed to evaluate the mental health outcomes of health care workers (HCWs) of the Verona academic hospital trust (Italy) one year after the outbreak of COVID-19 and to identify predicted risk factors. A web-based survey was conducted from mid-April to mid-May 2021 on hospital workers one year after the first evaluation performed during the lock-down phase of the COVID-19 pandemic. Post-traumatic stress, general anxiety, depression, and burnout were assessed by using, respectively, the impact of event scale (IES-R), the self-rating anxiety scale (SAS), the patient health questionnaire (PHQ-9) and the Maslach burnout inventory-general survey (MBI-GS). Multivariate logistic regression analysis was performed to identify factors associated with each of the four mental health outcomes one year after the COVID-19 outbreak. A total of 1033 HCWs participated. The percentage of HCWs scoring above the cut-off increased from 2020 to 2021 in all of the outcome domains (anxiety, 50.1% vs. 55.7, p < 0.05; depression, 26.6% vs. 40.6%, p < 0.001; burnout, 28.6% vs. 40.6%, p < 0.001; chi-square test), with the exception of post-traumatic distress. There was also an increase when stratifying by occupation and workplace, with a greater increase for depression and burnout. Multivariate analysis revealed that, one year after the COVID-19 outbreak, nurses were at the greatest risk of anxiety and depression, whereas residents were at the greatest risk of burnout (in terms of low professional efficacy). Working in intensive care units was associated with an increased risk of developing severe emotional exhaustion and a cynical attitude towards work.

Background: To report the baseline phase of the SIEROEPID study on SARS-CoV-2 infection seroprevalence among health workers at the University Hospital of Verona, Italy, between spring and fall 2020, to compare performances of several laboratory tests for SARS-CoV-2 antibody detection. Methods: 5299 voluntary health workers were enrolled from 28 April 2020 to 28 July 2020 to assess immunological response to SARS-CoV-2 infection throughout IgM, IgG and IgA serum levels titration by four laboratory tests. Association of antibody titre with several demographic variables, swab tests and performance tests (sensitivity, specificity, and agreement) were statistically analyzed. Results: The overall seroprevalence was 6%, considering either IgG and IgM, and 4.8% considering IgG. Working in COVID-19 Units was not associated with a statistically significant increase in the number of infected workers. Cohen’s kappa of agreement between MaglumiTM and VivaDiagTM was quite good when considering IgG only (Cohen’s kappa = 78.1%, 95% CI 74.0–82.0%), but was lower considering IgM (Cohen’s kappa = 13.3%, 95% CI 7.8–18.7%). Conclusion: The large sample size with high participation (84.7%), the biobank and the longitudinal design were significant achievements, offering a baseline dataset as the benchmark for risk assessment, health surveillance and management of SARS-CoV-2 infection for the hospital workforce, especially considering the ongoing vaccination campaign. Study results support the national regulator guidelines on using swabs for SARS-CoV-2 screening with health workers and using the serological tests to contribute to the epidemiological assessment of the spread of the virus.

Background: Few studies have modeled smoking histories by combining smoking intensity and duration to show what profile of smoking behavior is associated with highest risk of bladder cancer. This study aims to provide insight into the association between smoking exposure history and bladder cancer risk by modeling both smoking intensity and duration in a pooled analysis.Methods: We used data from 15 case-control studies included in the bladder cancer epidemiology and nutritional determinants study, including a total of 6,874 cases and 17,727 controls. To jointly interpret the effects of intensity and duration of smoking, we modeled excess odds ratios per pack-year by intensity continuously to estimate the risk difference between smokers with long duration/low intensity and short duration/high intensity.Results: The pattern observed from the pooled excess odds ratios model indicated that for a fixed number of pack-years, smoking for a longer duration at lower intensity was more deleterious for bladder cancer risk than smoking more cigarettes/day for a shorter duration. We observed similar patterns within individual study samples.Conclusions: This pooled analysis shows that long duration/low intensity smoking is associated with a greater increase in bladder cancer risk than short duration/high intensity smoking within equal pack-year categories, thus confirming studies in other smoking-related cancers and demonstrating that reducing exposure history to a single metric such as pack-years was too restrictive.

Objectives Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Pfizer Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), anti-S1/S2 and anti-RBD IgG, anti-RBD and anti-N/S1 IgM, and anti-S1 IgA. Results All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG levels increased between 91 and 368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ∼30-, ∼8- and ∼8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ∼50 days after the first vaccine dose. Anti-S1 IgA levels increased between 7 and 11 days after the first dose, slightly declined before the second dose, after which levels augmented by ∼24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4- to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all-time points. Conclusions BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving anti-SARS-Cov-2 IgG and IgA, magnified by the second vaccine dose.

ObjectiveTo determine burn-out levels and associated factors among healthcare personnel working in a tertiary hospital of a highly burdened area of north-east Italy during the COVID-19 pandemic.DesignObservational study conducted from 21 April to 6 May 2020 using a web-based questionnaire.SettingResearch conducted in the Verona University Hospital (Veneto, Italy).ParticipantsOut of 2195 eligible participants, 1961 healthcare workers with the full range of professional profiles (89.3%) completed the survey.Primary outcome measureLevels of burn-out, assessed by the Maslach Burnout Inventory-General Survey (MBI-GS). Multivariable logistic regression analysis was performed to identify factors associated with burn-out in each MBI-GS dimension (emotional exhaustion, EX; professional efficacy, EF; cynicism, CY).ResultsOverall, 38.3% displayed high EX, 46.5% low EF and 26.5% high CY. Burn-out was frequent among staff working in intensive care units (EX 57.0%; EF 47.8%; CY 40.1%), and among residents (EX 34.9%; EF 63.9%; CY 33.4%) and nurses (EX 49.2%; EF 46.9%; CY 29.7%). Being a resident increased the risk of burn-out (by nearly 2.5 times) in all the three MBI subscales and being a nurse increased the risk of burn-out in the EX dimension in comparison to physicians. Healthcare staff directly engaged with patients with COVID-19 showed more EX and CY than those working in non-COVID wards. Finally, the risk of burn-out was higher in staff showing pre-existing psychological problems, in those having experienced a COVID-related traumatic event and in those having experienced interpersonal avoidance in the workplace and personal life.ConclusionsBurn-out represents a great concern for healthcare staff working in a large tertiary hospital during the COVID-19 pandemic and its impact is more burdensome for front-line junior physicians. This study underlines the need to carefully address psychological well-being of healthcare workers to prevent the increase of burn-out in the event of a new COVID-19 healthcare emergency.

Objectives The COVID-19 pandemic is putting a huge strain on the provision and continuity of care. The length of sickness absence of the healthcare workers as a result of SARS-CoV-2 infection plays a pivotal role in hospital staff management. Therefore, the aim of this study was to explore the timing of COVID-19 recovery and viral clearance, and its predictive factors, in a large sample of healthcare workers. Study design Retrospective cohort study. Methods The analysis was conducted on data collected during the hospital health surveillance programme for healthcare staff at the University Hospital of Verona; healthcare workers were tested for SARS-CoV-2 through RT-PCR with oro-nasopharyngeal swab samples. The health surveillance programme targeted healthcare workers who either had close contact with SARS-CoV-2 infected patients or were tested as part of the screening-based strategy implemented according to national and regional requirements. Recovery time was estimated from the first positive swab to two consecutive negative swabs, collected 24 hours apart, using survival analysis for both right-censored and interval-censored data. Cox proportional hazard was used for multivariate analysis. Results During the health surveillance programme, 6455 healthcare workers were tested for SARS-CoV-2 and 248 (3.8%, 95% confidence interval [CI] 3.4–4.3) reported positive results; among those who tested positive, 49% were asymptomatic, with a median age of 39.8 years, which is significantly younger than symptomatic healthcare workers (48.2 years, p < 0.001). Screening tests as part of the health surveillance programme identified 31 (12.5%) of the positive cases. Median recovery time was 24 days (95% CI 23–26) and 21.5 days (95% CI 15.5–30.5) in right- and interval-censoring analysis, respectively, with no association with age, sex or presence of symptoms. Overall, 63% of participants required >20 days to test negative on two consecutive swabs. Hospitalised healthcare workers (4.8%) were older and had a significantly longer recovery time compared with non-hospitalised healthcare workers in both analyses (33.5 vs 24 days, p = 0.005). Conclusions Recovery from COVID-19 and viral clearance may take a long time, especially in individuals who are hospitalised. To detect asymptomatic cases, screening programmes for healthcare workers is recommended.

Objectives The ongoing outbreak of coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses formidable challenges to all health care systems. Serological assays may be used for improving disease management when appropriately applied, for investigating the antibody responses mounted against SARS-CoV-2 infection and for assessing its real prevalence. Although testing the whole population is impractical, well-designed serosurveys in selected subpopulations in specific risk groups may provide valuable information. We evaluated the prevalence of SARS-CoV-2 infection in health care workers (HCW) who underwent molecular testing with reverse transcription real-time polymerase chain reaction (rRT-PCR) in the main hospitals of the Veneto Region of Italy by measuring specific antibodies (Abs). Methods Both immunoglobulin (Ig)M and IgG antibodies against SARS-Cov-2 S-antigen and N-protein were measured using a validated chemiluminescent analytical system (CLIA) called Maglumi™ 2000 Plus (New Industries Biomedical Engineering Co., Ltd [Snibe], Shenzhen, China). Results A total of 8,285 HCW were tested. SARS-CoV-2 specific antibodies (IgM, IgG or both) were detectable in 378 cases (4.6%, 95% CI 4.1–5.0%). Seroconversion was observed in 4.4% of women vs. 5.0% of men, but this difference was not significant. Although detectable antibodies were found in all HCW who developed severe COVID-19 infection (100%), lower seropositivity was found in mild disease (83%) and the lowest prevalence (58%) was observed in asymptomatic subjects. Conclusions Seroprevalence surveys are of utmost importance for understanding the rate of population that has already developed antibodies against SARS-CoV-2. The present study defined precisely the circulation of SARS-CoV-2 in a cohort of HCW in the Veneto Region, with its prevalence (4.6%) reflecting a relatively low circulation. Symptomatic individuals or those hospitalized for medical care were 100% antibody positive, whilst Abs were only detectable in 58% of asymptomatic carriers.

Italy presented the first largest COVID-19 outbreak outside of China. Veneto currently ranks fourth among the Italian regions for COVID-19 confirmed cases (~19,000). This study presents health surveillance data for SARS-CoV-2 in 6100 health workers (HW) employed in a large public hospital. Workers underwent oropharyngeal and nasopharyngeal swabs, with a total of 5942 participants (97.5% of the population). A total of 11,890 specimens were tested for SARS-CoV-2 infection using PCR, identifying the viral genes E, RdRP, and N. Positive tests were returned for 238 workers (cumulative incidence of 4.0%, similar in both COVID and nonCOVID units). SARS-CoV-2 risk was not affected by gender, age, or job type, whereas work setting and occupation were both predictors of infection. The risk was higher in medical wards (OR 2.7, 95% CI 1.9&ndash, 3.9) and health services (OR 4.3, 95% CI 2.4&ndash, 7.6), and lower in surgical wards and administration areas. To our knowledge, this study represents the largest available HW case list swab-tested for SARS-CoV-2, covering almost the total workforce. Mass screening enabled the isolation of HW, improved risk assessment, allowed for close contacts of and infected HW to return to work, provided evidence of SARS-CoV-2 diffusion, and presented solid ground to prevent nosocomial SARS-CoV-2 infections. The ongoing concurrent sero-epidemiological study aims to enable the improvement of health surveillance to maintain the safety of HWs and the communities they serve.

Interventional radiology activities and other medical practices using ionising radiation have become increasingly prevalent. In this context, the use of anti-X aprons, in association with awkward postures and non-ergonomic working conditions, might cause the onset of musculoskeletal disorders (MSDs). This research aims to evaluate the evidence about the correlation between wearing anti-X aprons and work-related MSDs. A systematic scoping review of articles published between 1990 and 2020 was conducted by searching the PubMed, Scopus, Embase, and Web of Science databases. Twelve cross-sectional studies, conducted among interventional physicians, nurses, and technicians, were finally included. Five studies primarily investigated the association between use of anti-X aprons and MSDs, showing that a higher prevalence of disorders was not always associated with the use of protective aprons. No studies investigated the impact of anti-X aprons on fitness for work assessment, particularly in subjects with MSDs. There is no complete agreement about the correlation between anti-X apron-wearing and the occurrence of MSDs, although the possible discomfort of workers using anti-X aprons appears more evident. Further studies are needed to objectify the role of these protective devices in the genesis of MSDs and to offer specific ergonomic solutions for healthcare workers.

Background During the COVID-19 pandemic, swab tests proved to be effective in containing the infection and served as a means for early diagnosis and contact tracing. However, little evidence exists regarding the correct timing for the execution of the swab test, especially for asymptomatic individuals and health care workers. Objective The objective of this study was to analyze changes in the positive findings over time in individual SARS-CoV-2 swab tests during a health surveillance program. Methods The study was conducted with 2071 health care workers at the University Hospital of Verona, with a known date of close contact with a patient with COVID-19, between February 29 and April 17, 2020. The health care workers underwent a health surveillance program with repeated swab tests to track their virological status. A generalized additive mixed model was used to investigate how the probability of a positive test result changes over time since the last known date of close contact, in an overall sample of individuals who tested positive for COVID-19 and in a subset of individuals with an initial negative swab test finding before being proven positive, to assess different surveillance time intervals. Results Among the 2071 health care workers in this study, 191 (9.2%) tested positive for COVID-19, and 103 (54%) were asymptomatic with no differences based on sex or age. Among 49 (25.7%) cases, the initial swab test yielded negative findings after close contact with a patient with COVID-19. Sex, age, symptoms, and the time of sampling were not different between individuals with an initial negative swab test finding and those who initially tested positive after close contact. In the overall sample, the estimated probability of testing positive was 0.74 on day 1 after close contact, which increased to 0.77 between days 5 and 8. In the 3 different scenarios for scheduled repeated testing intervals (3, 5, and 7 days) in the subgroup of individuals with an initially negative swab test finding, the probability peaked on the sixth, ninth and tenth, and 13th and 14th days, respectively. Conclusions Swab tests can initially yield false-negative outcomes. The probability of testing positive increases from day 1, peaking between days 5 and 8 after close contact with a patient with COVID-19. Early testing, especially in this final time window, is recommended together with a health surveillance program scheduled in close intervals.

The main aim of the present study was to summarize the available literature on the topic of occupational health and safety (OH&S) among immigrant workers (IMWs) in Italy and Spain. We conducted a scoping review, searching Medline, Social Sciences Citation Index, PsycINFO, CINAHL Plus, SciELO, and EMBASE for peer-reviewed articles, published in English, Italian, or Spanish, between 1999–2018. 34 studies were included, 28 with quantitative methodology and 6 with qualitative. Main findings were that, compared to natives, IMWs in Italy and Spain showed higher prevalence of low-skilled jobs and of perceived discrimination at work; higher physical demands, poorer environmental working conditions, and more exposure to occupational risks (e.g., ergonomic and psychosocial hazards); a greater risk of occupational injuries; worse general and mental health; and a plausible worsening of their health status, especially in Spain, as a result of the economic crisis. The findings of the present scoping review constitute warning signs that indicate the need for a holistic global response to ensure that adverse OH&S outcomes among IMWs workers are improved and that equitable access to health care is guaranteed. Such a response will require a concrete and evidence-based approach to prevent and monitor occupational risk factors and associated outcomes in the workplaces.

Background: Migrant workers (MWs) generally perform dangerous jobs and have reduced access to occupational health (OH) care, therefore being prone to developing occupational diseases (OD). The aim of the work is to describe a case series of MWs and report on related outcomes for OH professionals. Methods: A case series of 724 MWs, sent from January 2001 to June 2013 to a public OH unit for OD or fitness-for-work (FFW) evaluation, was entered in a dedicated database and elaborated for descriptive statistics with Microsoft Excel. Results: MWs were mostly (75%) men, with a mean age of 40. They came mainly from Morocco, Senegal, Albania, Romania, and Pakistan. Main sectors of employment were manufacturing, metal industry, services, construction. OD were found in 210 cases, main diagnoses being: Lumbar disc and upper limb musculoskeletal disorders (51%), contact dermatitis (15%), allergic asthma (8%), noise-induced hearing loss (7%), tumors (3%), psychiatric disorders (2%). Moreover, 136 FFW judgements were formulated, with some limitations/restrictions expressed. Finally, a relevant prevalence of some chronic non-occupational diseases was found. Conclusions: MWs in Italy may suffer from OH inequalities. Qualified public OH professionals and occupational physicians in workplaces should have a proactive role to concretely meet MWs&rsquo, health needs.

Objectives. To deal with biohazards in research laboratories (RL), identify exposure features, types and incidence of laboratory-acquired infections/diseases (LAI), and prevention strategies. Methods. Literature search and appraisal, non-systematic, last 40 years; legislation, guidelines and good practices evaluation. Results. Biohazards are relevant in RL, in various biomedical, agri-food and industrials sectors, with a variety of LAI (especially viruses and bacteria), modes of exposure and transmission; LAI decrease after preventive measures, vaccinations and clinical treatments; LAI underestimation, due to underreporting and subclinical LAI; need to implement and comply with well-known and available technical and scientific guidelines, good medical and laboratory practices; need for specific health education and training; lack of reporting and epidemiologic surveillance systems, with consequent limited data on risk assessment and effectiveness of preventive interventions. Conclusions. The roles of the occupational physician must be underlined, especially for risk assessment, health and clinicepidemiologic surveillance, with the need to monitor seconeffectiveness of preventive interventions, particularly for biosafety and biosecurity levels in RL. It should be useful to increase capacity of epidemiologic surveillance for LAI, through networking or dedicated websites, in order to collect and analyze accidents, injuries, infections, or adverse events occurred to workers in RL.Obiettivi. Trattare del rischio biologico (RB) nei laboratori di ricerca (LR), identificarne peculiarità per caratteristiche di esposizione, incidenza e tipologia di infezioni/malattie correlate (LAI) e per strategie preventive. Metodi. Ricerca e valutazione bibliografica non sistematica, ultimi 40 anni; valutazione legislazione, linee guida, buone prassi. Risultati. Emerge un RB nei LR in vari settori produttivi biomedici, agroalimentari, industriali, con varietà di LAI (soprattutto virus e batteri), di modalità di esposizione e trasmissione; riduzione delle LAI per misure preventive, efficacia trattamenti clinici e vaccinazioni, ma anche sottostima, per inadeguato reporting e LAI subcliniche; necessità di implementazione ed adesione a note linee guida tecnico-scientifiche e buone prassi già disponibili; necessità di informazione, formazione e addestramento specifici; assenza di sistemi di reporting e sorveglianza epidemiologica strutturati, con conseguente limitazione di dati su valutazione del rischio ed efficacia dei sistemi preventivi. Conclusioni. Si ribadisce il ruolo del medico del lavoro in particolare per valutazione del rischio, sorveglianza sanitaria e clinico-epidemiologica, con necessità di monitorare l’efficacia degli interventi di prevenzione, in particolare dei livelli di biosicurezza. Utile migliorare la capacità di sorveglianza epidemiologica delle LAI, ad esempio attraverso networking o portali dedicati a segnalazioni di infortuni, malattie ed eventi avversi occorsi ai lavoratori dei LR.

The main risk factor for bladder cancer (BC) is cigarette smoking, but also occupational exposure to carcinogens is relevant, causing about 4–10% of BC. We aimed at investigating the association between BC risk, occupations held in the past and exposure to occupational carcinogens, also assessing whether these associations were influenced by tumour grade. We pooled data from two Italian case–control studies on male BC, analyzing 893 cases and 978 controls. Occupations were classified using the International Standard Classification of Occupations and exposure to carcinogens was assigned using a validated Job Exposure Matrix. Logistic regression approach was used as well as a semi-Bayesian model, based on a priori information on exposure. A significantly increased BC risk was found for chemical engineering technicians, postmen, and lathe operators, but only, for the latter, the association remained significant after Bayesian control for type I error. Among carcinogens, cadmium and trichloroethylene were associated with BC. When analyzing data by grade, exposure to these carcinogens was associated with low-grade BC only. Our results suggest that monitoring workplaces to prevent exposure to carcinogenic agents is still an important task, which should be still given adequate importance in public health.

Introduction: Additional or better markers are needed to guide the clinical monitoring of patients with non-muscle-invasive bladder cancer (NMIBC). Aim: To investigate the influence of occupational exposures and genetic polymorphisms on recurrence and progression of NMIBC. Methods: The study includes 160 NMIBC patients. We collected on questionnaire information on demographic variables, lifetime smoking history, lifetime history of occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons. Genetic polymorphism (glutathione S-transferase M1, T1, P1 (GSTM1, GSTT1, GSTP1), N-acetyltransferase 1, 2 (NAT1, NAT2), cytochrome P450 1B1 (CYP1B1), sulfotransferase 1A1 (SULT1A1), myeloperoxidase (MPO), catechol-O-methyltransferase (COMT), manganese superoxide dismutase (MnSOD), NAD(P)H:quinone oxidoreductase (NQO1), X-ray repair cross-complementing group 1, 3 (XRCC1, XRCC3) and xeroderma pigmentosum complementation group (XPD)) was assessed in peripheral blood lymphocytes. DNA adducts were evaluated by 32P-postlabeling. Predictors of recurrence (histological confirmation of a newly found bladder tumor) and progression (transition of tumor from low-grade to high-grade and/or increase in TNM stage) were identified by multivariate Cox proportional hazard regression with stepwise backward selection of independent variables. Hazard ratios (HR) with 95% confidence interval (95%CI) and two-tail probability of error (p-value) were estimated. Results: The risk of BC progression decreased with the homozygous genotype &ldquo, ValVal&rdquo, of both COMT and MnSOD (HR = 0.195, 95%CI = 0.060 to 0.623, p = 0.006). The results on BC recurrence were of borderline significance. No occupational exposure influenced recurrence or progression. Conclusion: Our results are supported by experimental evidence of a plausible mechanism between cause (ValVal genotype of both MnSOD and COMT) and effect (decreased progression of tumor in NMIBC patients). The genetic polymorphisms associated with better prognosis may be used in clinic to guide selection of treatment for patients initially diagnosed with NMIBC. However, external validation studies are required.

Background: Telomere length (TL) maintenance plays an important role in bladder cancer (BC) and prognosis. However the manifold influence of everyday life exposures and genetic traits on leucocyte TL (LTL), is not fully elucidated. Methods: Within the framework of a hospital-based case (n = 96)/control (n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Data on lifetime smoking, alcohol and coffee drinking, dietary habits and occupational exposures, pointing to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) were collected. Structural equation modelling (SEM) analysis appraised this complex relationships. Results: The SEM analysis indicates negative direct links (p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk (p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. There was evidence of indirect effects (p < 0.05) on BC risk, probably via LTL reduction, by age and NAT2 (positive link), MPO and XRCC3 (negative link). Conclusions: Our study supports evidence that LTL attrition is a critical event in BC. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention.

A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r2 ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09–1.27, P = 4.67 × 10−5] versus OR = 1.01 (95% CI, 0.93–1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (Ptrend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. Cancer Res; 74(20); 5808–18. ©2014 AACR.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and PConditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and PConditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10(-15) and PConditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 x 10(-18) and PConditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Occupational injuries are a relevant research and practical issue. However, intervention studies evaluating the effectiveness of workplace injury prevention programs are seldom performed.The effectiveness of a multifaceted intervention aimed at reducing occupational injury rates (incidence/employment-based=IR, frequency/hours-based=FR, severity=SR) was evaluated between 2008 and 2013 in 29 Italian foundries (22 ferrous; 7 non-ferrous; 3,460 male blue collar workers/year) of varying sizes. Each foundry established an internal multidisciplinary prevention team for risk assessment, monitoring and prevention of occupational injuries, involving employers, occupational physicians, safety personnel, workers' representatives, supervisors. Targets of intervention were workers, equipment, organization, workplace, job tasks. An interrupted time series (ITS) design was applied.4,604 occupational injuries and 83,156 lost workdays were registered between 2003 and 2013. Statistical analysis showed, after intervention, a reduction of all injury rates (-26% IR, -15% FR, -18% SR) in ferrous foundries and of SR (-4%) in non-ferrous foundries. A significant (p=0.021) 'step-effect' was shown for IR in ferrous foundries, independent of secular trends (p0.001). Sector-specific benchmarks for all injury rates were developed separately for ferrous and non-ferrous foundries.Strengths of the study were: ITS design, according to standardized quality criteria (i.e., at least three data points before and three data points after intervention; clearly defined intervention point); pragmatic approach, with good external validity; promotion of effective good practices. Main limitations were the non-randomized nature and a medium length post-intervention period. In conclusion, a multifaceted, pragmatic and accountable intervention is effective in reducing the burden of occupational injuries in small-, medium- and large-sized foundries. Practical Applications: The study poses the basis for feasible good practice guidelines to be implemented to prevent occupational injuries, by means of sector-specific numerical benchmarks, with potentially relevant impacts on workers, companies, occupational health professionals and society at large.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC. info:eu-repo/grantAgreement/EC/FP7/018827 info:eu-repo/grantAgreement/EC/FP7/218071 Radboud University Nijmegen Medical Centre (RUNMC) Prinses Beatrix Fonds VSB Fonds National Institute of Mental Health (NIH/NIMH) MH078075 Cancer Research UK Yorkshire Cancer Research European Union 513943 Compagnia di San Paolo-Human Genetics Foundation (HuGeF) Italian Association for Cancer Research, Italy Piedmont Region Progetti di Ricerca Sanitaria Finalizzata Flemish government Belgian province of Limburg Swedish Cancer Society Swedish Research Council Shiraz Institute for Cancer Research Shiraz, Iran ICR-87-502 Red Tematica de Investigacion Cooperativa en Cancer RD06/0020/1054

Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 × 10 12). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC. © 2010 Nature America, Inc. All rights reserved., Vlaamse regering 513943 Compagnia di San Paolo Yorkshire Cancer Research Adessium Foundation European Commission: LSHC-CT-2005 218071 Associazione Italiana per la Ricerca sul Cancro Prinses Beatrix Spierfonds, We thank the individuals who participated in the study and whose contribution made this work possible. We also thank the nurses at deCODE’s recruitment center and the personnel at the deCODE core facilities. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the Icelandic UBC cases. C.Z. and S.B. are funded by a FP7-MC-IAPP Grant agreement no. 218071 (CancerGene). Collection of samples and data in Iceland and The Netherlands was funded in part by the European Commission (POLYGENE: LSHC-CT-2005) and a research investment grant of the Radboud University Nijmegen Medical Centre. Control samples for the Dutch follow-up group were genotyped with generous support from the ‘Prinses Beatrix Fonds’, VSB Fonds, H. Kersten and M. Kersten (Kersten Foundation), The Netherlands ALS Foundation, J.R. van Dijk and the Adessium foundation. The controls from the Dutch Schizophrenia GWA study were genotyped with the support of the US National Institute of Mental Health (R.A.O.). The Leeds Bladder Cancer Study was funded by Cancer Research UK and Yorkshire Cancer Research. The Torino Bladder Cancer Case Control Study was supported by a grant to ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union Sixth Framework Program, Priority 5:‘Food Quality and Safety’ (Contract No. 513943), and by grants of the Compagnia di San Paolo, of the Italian Association for Cancer Research and of the Piedmont Region Progetti de Ricerca Sanitaria Finalizzata, Italy. The Belgian case-control study on bladder cancer risk was supported by a grant of the Flemish government, the government of the Belgian province of Limburg and the Limburg Cancer Fund., 1Department of Epidemiology, Biostatistics and Health Technology Assessment and 2Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 3Comprehensive Cancer Center East, Nijmegen, The Netherlands. 4deCODE Genetics, Reykjavik, Iceland. 5Section of Epidemiology and Biostatistics and 6Section of Experimental Oncology, Leeds Institute of Molecular Medicine, St. James’s University Hospital, Leeds, UK. 7Christie Hospital National Health Service Foundation Trust, Manchester, UK. 8Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 9National Institute of Environmental Health, Budapest, Hungary. 10Environmental Health Centre, Cluj-Napoca, Romania. 11State Health Institute, Banska Bystrica, Slovakia. 12Institute for Scientific Interchange (ISI) Foundation, Torino, Italy. 13Department of Epidemiology and Public Health, Imperial College, London, UK. 14Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Italy. 15Unit of Cancer Epidemiology, University of Torino, Torino, Italy. 16Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Torino, Italy. 17Department of Experimental and Applied Medicine, Section of Occupational Medicine and Industrial Hygiene, University of Brescia, Brescia, Italy. 18Unit of Genetic Epidemiology, Department of Public Health and Epidemiology, University of Birmingham, Birmingham, UK. 19Department of Complex Genetics, Cluster of Genetics and Cell Biology, Nutrition and Toxicology Research Institute, Maastricht University, Maastricht, The Netherlands. 20Leuven University Centre for Cancer Prevention (LUCK), Leuven, Belgium. 21Department of Medicine, University of Zaragoza, Zaragoza, Spain. 22Division of Urology, San Jorge Hospital, Huesca, Spain. 23Division of Urology, Hospital Clinico, Zaragoza, Spain. 24Department of Urology, University of Zaragoza School of Medicine, Zaragoza, Spain. 25Division of Surgical Pathology, San Jorge Hospital, Huesca, Spain. 26Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany. 27Department of Urology, Paul Gerhardt Foundation, Lutherstadt Wittenberg, Germany. 28Department of Medical Genetics, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. 29University of California Los Angeles Center for Neurobehavioral Genetics, Los Angeles, USA. 30Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. 31Department of Medical Oncology, 32Department of Urology and 33Department of Pathology, Landspitali–University Hospital, Reykjavik, Iceland. 34Department of Urology, Zonguldak Karaelmas University, Zonguldak, Turkey. 35Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 36Department of General Practice, Catholic University of Leuven, Leuven, Belgium. 37Department of General Practice, Maastricht University, Maastricht, The Netherlands. 38Division of Medical Oncology, University of Zaragoza, Zaragoza, Spain. 39Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany. 40Section of Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. 41Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy, Gothenburg, Sweden. 42Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK. 43Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 44These authors contributed equally to this work. Correspondence should be addressed to L.A.K. (b.kiemeney@ebh.umcn.nl) or K.S. (kstefans@decode.is).

Contains fulltext : 81560.pdf (Publisher’s version ) (Closed access) The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

The aim of the study was to investigate NAT1, NAT2, GSTM1, GSTT1, GSTP1, SULT1A1, XRCC1, XRCC3 and XPD genetic polymorphisms, coffee consumption and risk of bladder cancer (BC) through a hospital-based case-control study. The study population included 197 incident BC cases and 211 controls. The association between genetic polymorphisms, coffee drinking and BC risk was assessed by logistic regression taking into account age, education, tobacco smoking and occupational exposures to polycyclic aromatic hydrocarbons and aromatic amines. No association was found between the genetic polymorphisms investigated and BC risk according to coffee consumption apart of a significant increased BC risk among GSTP1 105-114 Val carriers heavy coffee drinkers (3 cups/day) (OR 3.18, 95% CI 1.06-9.55). In conclusion our findings suggest a very limited role, if any, of genetic polymorphisms investigated in modulating the BC risk in coffee drinkers.

Contains fulltext : 167299.pdf (Publisher’s version ) (Closed access) Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 x 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 x 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 x 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P

Occupational exposure to lung carcinogens is and was common in workplaces. 5–25 % of lung cancers (LCs) could be causally attributable to occupation; however, LC underreporting and undercompensation are widespread, with remarkable tolls paid by individuals and society. This work aims to: describe an ongoing hospital-based systematic search (SS) of occupational LC; improve aetiological diagnosis; increase number and quality of LC notifications. Through a short form, physicians at a public hospital referred incident LC to the Occupational Health Unit (OHU). Only patients selected through the form were interviewed; a personal, occupational and clinical history was collected; reports were sent to the ward and Local Health Authority, with aetiological diagnosis criteria and probability of causation. From 1998 to 2013, 3274 cases of LC were notified to the OHU; prior to the system, just couple of dozens were assessed. A total of 1522 patients were fully interviewed; in 395 cases, causation was attributed to occupation (26 % of interviewed patients); all were notified to authorities, as compared to the handful reported before the system was adopted. Main aetiological agents were silica, asbestos, polycyclic aromatic hydrocarbons, truck driving, painting, multiple exposures. Compensation rate was remarkable (39 %). Through SS, many occupational LCs were found that otherwise would have been lost. Aetiological diagnosis proved to be rich of scientific advantages and practical implications, with attention to equity and social aspects. SS was easy, accountable and fostered multidisciplinary collaboration among medical specialties, significantly reducing underreporting and undercompensation of occupational LC.

Tobacco smoking and occupational exposure are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines, which lead to oxidative stress and DNA damage. Several enzymes, which play key roles in oxidative stress are polymorphic in humans. Myeloperoxidase (MPO) produces a strong oxidant for microbicidal activity, and activates carcinogens in tobacco smoke. Catechol-O-methyltransferase (COMT) catalyzes the methylation of endo- and xenobiotics and prevents redox cycling. NAD(P)H:quinone oxidoreductase (NQO1) catalyzes the two-electron reduction of quinoid compounds, which also protects cells from redox cycling. Manganese superoxide dismutase (MnSOD) protects cells from free radical injury. To test the hypothesis that the risk of bladder cancer can be influenced by polymorphisms in the genes that modulate oxidative stress, in particular by interacting with environmental carcinogens, we conducted a hospital-based case-control study among men in Brescia, Northern Italy. We recruited and interviewed 201 incident cases and 214 controls from 1997 to 2000. Occupational exposures to PAHs and aromatic amines were coded blindly by occupational physicians. Unconditional multivariate logistic regression was applied to model the association between genetic polymorphisms and bladder cancer risk and the effect of modifications of smoking and occupational exposures were evaluated. MPO G-463A homozygous variant was associated with a reduced risk of bladder cancer with an OR of 0.31 (95% CI = 0.12-0.80). MnSOD Val/Val genotype increased the risk of bladder cancer with OR of 1.91 (95% CI = 1.20-3.04), and there was a combined effect with smoking (OR = 7.20, 95% CI = 3.23-16.1) and PAH (OR = 3.02,95% CI = 1.35-6.74). We did not observe an effect of COMT Val108Met polymorphism. These findings suggest that individual susceptibility of bladder cancer may be modulated by MPO and MnSOD polymorphisms, and that the combination of genetic factors involved in oxidative stress response with environmental carcinogens may play an important role in bladder carcinogenesis. © Oxford University Press 2004; all rights reserved.

Objectives: We examined which occupations and industries are currently at high risk for bladder cancer in men. Methods: We combined data from 11 case–control studies conducted between 1976–1996 in six European countries. The study comprised 3346 incident cases and 6840 controls, aged 30–79 years. Lifetime occupational and smoking histories were examined using common coding. Results: Odds ratios for eight a priori defined high-risk occupations were low, and with the exception of metal workers and machinists (OR = 1.16, 95% CI = 1.02–1.32), were not statistically significant. Higher risks were observed for specific categories of painters, metal, textile and electrical workers, for miners, transport operators, excavating-machine operators, and also for non-industrial workers such as concierges and janitors. Industries entailing a high risk included salt mining, manufacture of carpets, paints, plastics and industrial chemicals. An increased risk was found for exposure to PAHs (OR for highest exposure tertile = 1.23, 95% CI = 1.07–1.4). The risk attributable to occupation ranged from 4.2 to 7.4%, with an estimated 4.3% for exposure to PAHs. Conclusions: Metal workers, machinists, transport equipment operators and miners are among the major occupations contributing to occupational bladder cancer in men in Western Europe. In this population one in 10 to one in 20 cancers of the bladder can be attributed to occupation.

Contains fulltext : 138103.pdf (Publisher’s version ) (Closed access) Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 x 10(-11) for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS.

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10(-) (5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 × 10(-) (7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 × 10(-) (7)). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.

Background: In studies in men, risk estimates on occupation and bladder cancer are distorted by about 10% when not adjusting for smoking. We examined the degree to which occupational risk estimates for bladder cancer in women are confounded by smoking, and the degree of residual confounding by inadequate control of this effect. Methods: Primary data of 11 case-control studies on occupation and bladder cancer from Denmark, France, Germany, Greece, Italy, and Spain were pooled. Information for smoking and lifetime occupational history for 700 female cases and 2,425 female controls ages 30–79 was abstracted and recoded. Logistic regression was used to calculate odds ratios (OR) by occupation, applying five models which differed in their degree of adjustment for smoking. Results: In major occupational groups, risk estimates were distorted by less than 10% when not adjusting for smoking. A statistically significant excess risk for bladder cancer was found in 13 specific occupations and industries. In most occupations, adjustment for smoking led the ORs towards the null value, but all statistically significant associations were maintained after adjustment. In three occupations (lathe operators, field crop workers, and wood manufacturers), a statistically significant excess risk was masked when not adjusting for smoking. In six occupations, estimates were distorted by more than 10% (−22% up to +40%). In occupations where smoking acted as a positive confounder, the proportion of confounding removed using a dichotomous smoking variable (ever/never) was around 60%. In one occupation (buyers), controlling for smoking status (ever, never) led to over-adjustment, because the percentage of smokers was high but the quantity smoked was low. Conclusions: Tobacco smoking was not found to be a major confounder for the association between occupation and bladder cancer in women. Most of this confounding effect could be removed by adjustment by smoking status (ever/never), without consideration of amount or duration of smoking. Am. J. Ind. Med. 36:75–82, 1999. © 1999 Wiley-Liss, Inc.

BACKGROUND: Pigs play a key epidemiologic role in the ecology of influenza A viruses (IAVs) emerging from animal hosts and transmitted to humans. Between 2008 and 2010, we investigated the health risk of occupational exposure to swine influenza viruses (SIVs) in Italy, during the emergence and spread of the 2009 H1N1 pandemic (H1N1pdm) virus. METHODOLOGY/PRINCIPAL FINDINGS: Serum samples from 123 swine workers (SWs) and 379 control subjects (Cs), not exposed to pig herds, were tested by haemagglutination inhibition (HI) assay against selected SIVs belonging to H1N1 (swH1N1), H1N2 (swH1N2) and H3N2 (swH3N2) subtypes circulating in the study area. Potential cross-reactivity between swine and human IAVs was evaluated by testing sera against recent, pandemic and seasonal, human influenza viruses (H1N1 and H3N2 antigenic subtypes). Samples tested against swH1N1 and H1N1pdm viruses were categorized into sera collected before (n. 84 SWs; n. 234 Cs) and after (n. 39 SWs; n. 145 Cs) the pandemic peak. HI-antibody titers ≥10 were considered positive. In both pre-pandemic and post-pandemic peak subperiods, SWs showed significantly higher swH1N1 seroprevalences when compared with Cs (52.4% vs. 4.7% and 59% vs. 9.7%, respectively). Comparable HI results were obtained against H1N1pdm antigen (58.3% vs. 7.7% and 59% vs. 31.7%, respectively). No differences were found between HI seroreactivity detected in SWs and Cs against swH1N2 (33.3% vs. 40.4%) and swH3N2 (51.2 vs. 55.4%) viruses. These findings indicate the occurrence of swH1N1 transmission from pigs to Italian SWs. CONCLUSION/SIGNIFICANCE: A significant increase of H1N1pdm seroprevalences occurred in the post-pandemic peak subperiod in the Cs (p

OBJECTIVES--A hospital based case-control study was conducted between 1992 and 1993 in the province of Brescia, a highly industrialised area in northern Italy, to evaluate occupational risk factors of bladder cancer. METHODS--The study evaluated 355 histologically confirmed cases of bladder cancer (275 men, 80 women) and 579 controls affected by urological non-neoplastic diseases (397 men, 182 women). Lifetime occupational history, smoking and drinking habits, and sociodemographic characteristics were recorded by means of a structured questionnaire. Odds ratios (ORs) were computed with adjustment for age, smoking, alcohol and coffee consumption, education, and place of residence. RESULTS--A significant (P < 0.05) increase of risk of bladder cancer were found in men for labourers in the construction industry (OR 2.1, 95% confidence interval (95% CI) 1.1-3.9) and for recreational and cultural services (OR 5.0, 95% CI 1.3-18.9). Increased risks, although not significant, were found for various other occupations and industries such as machinery mechanics, metal processers and polishers, blacksmiths, gunsmiths, painters; for transport workers, an increased risk with increasing duration of employment was found. CONCLUSIONS--Occupational exposures seem to contribute to bladder cancer risk in the area under study.

Highly pathogenic (HP) and low pathogenic (LP) avian influenza viruses (AIVs) belonging to H5 and H7 subtypes have been found to be associated with human infection as the result of direct transmission from infected poultry. Human infections by AIVs can cause mild or subclinical disease, and serosurveys are believed to represent an important tool to identify risk of zoonotic transmission. Therefore, we sought to examine Italian poultry workers exposed during LPAI and HPAI outbreaks with the aim of assessing serologic evidence of infection with H5 and H7 AIVs. From December 2008 to June 2010 serum samples were collected from 188 poultry workers and 379 nonexposed controls in Northern Italy. The hemagglutination inhibition (HI) assay using horse red blood cells (RBCs) and a microneutralization (MN)-enzyme-linked immunosorbent assay test were used to analyze human sera for antibodies against the following H5 and H7 LPAI viruses: A/Dk/It/4445/07(H5N2); A/Ty/It/2369/09(H5N7); A/Ty/It/218-193/ 10; A/Ck/It/3775/99(H7N1); A/Ty/It/214845/03(H7N3); and A/Dk/It/332145/09(H7N3). Since previous studies identified low antibody titer to AIVs in people exposed to infected poultry, a cutoff titer ofor = 1:10 was chosen for both serologic assays. Only HI-positive results confirmed by MN assay were considered positive for presence of specific antibodies. The Fisher exact test was used to analyze differences in seroprevalence between poultry workers and control groups, with the significance level set at P0.05. MN results showed a proportion of H7-seropositive poultry workers (6/188, i.e., 3.2%), significantly higher than that of controls (0/379), whereas no MN-positive result was obtained against three H5 LPAI subtypes recently identified in Italy. In conclusion, the survey indicated that assessing seroprevalence can be an important tool in risk assessment and health,surveillance of poultry workers.

Few intervention studies aimed at preventing occupational injuries (OI) are available, particularly in the foundry sector. Evaluation of effectiveness of an intervention to prevent OI was carried out in two foundries (cast-iron = A, non-ferrous = B). A multifaceted intervention was developed by a team composed of occupational physician, safety personnel and workers’ representatives. Intervention focused on safety procedures, education, health surveillance (HS), fitness for work and first aid. Mandatorily registered OI data were collected. Primary outcome was reduction in injury rates. Before–after, pre-peri-post and interrupted time series (ITS) analyses were performed. Secondary outcomes mainly regarded re-injury rates and lost workdays (LW) reduction, access to HS, implementation of good practices and insurance litigation costs. In 1997–2009, 556 and 97 OI occurred in A and B, accounting for 11,597 and 2,567 LW, respectively. A significant (P

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.

The aim of the project was to educate nursing staff on patient handling techniques to prevent low back pain. Within the framework of a multidisciplinary preventive intervention, a pre-post study design was implemented in a hospital. One hundred and forty nurses and healthcare assistants attended a two-hour lesson and a three-hour practical training session; 48 nurses attended a train-the-trainer programme that was comprised of three-hour classes, two-hour lessons on communication techniques and four hours of practical training. Improvements were tested using questionnaires and direct observations. A statistically significant improvement was noted in questionnaire scores (p

Cytochrome P4501A2 (CYP1A2) is a key enzyme for activation of bladder carcinogens. Polymorphisms in the 5'-noncoding promoter region of CYP1A2 gene [mainly -2467T/delT(rs35694136) and -163C/A(rs762551)], are crucial in modifying CYP1A2 activity in smokers. Within the framework of a hospital-based case/control study, we investigated the relationship between CYP1A2 polymorphisms, occupational/environmental exposures and bladder cancer (BC) risk. The study population included 185 BC cases and 180 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). A case-only design was applied to study the interaction between CYP1A2 -2467T/delT (or -163C/A) and occupational and environmental factors. Multiple logistic regression showed a significantly increased risk among heavy smokers (or =50 packyears; OR 5.6, 95% CI: 2.5-12.5) and heavy coffee drinkers (5 cups/day; OR 3.1, 95% CI: 1.2-7.9). Exposure to AAs showed a significant trend of BC risk with increasing cumulative exposure (CE) (P = 0.04), with heavy smoking as possible confounder. A decreased risk was noted for large leaf vegetable consumption, with significant trend from1/month to3 times/week (P = 0.008). The case-only analysis showed an interaction between -2467T/delT and tobacco smoking25 packyears (P = 0.04); no interaction was detected between such polymorphisms and coffee consumption, dietary habits and occupational exposure to AAs. No effects were shown with -163C/A genotype as well as no overall effect of CYP1A2 by itself on BC risk. This is the first study suggesting that CYP1A2 -2467T/delT modifies the effect of cigarette smoking on BC risk.

Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01-1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01-1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% CI, 1.00-1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. The TBCS was supported by a grant to ECNIS, a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘‘Food Quality and Safety’’ (contract no. 513943), by a grant of the Italian Association for Cancer Research, of the Piedmont Region Progetti di Ricerca Sanitaria Finalizzata, and of the Ministry of Health, Oncology Integrated Project ‘‘Cancer Primary Prevention in Italy: a research-based approach,’’ Italy.

Contains fulltext : 80627.pdf (Publisher’s version ) (Closed access) We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 x 10(-10) and the allelic odds ratio was 1.15 (95% confidence interval 1.10-1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus.

Contains fulltext : 71044.pdf (Publisher’s version ) (Closed access) We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7)).

The glutathione S-transferase P1 genotype (GSTP1) is involved in the inactivation of cigarette smoke carcinogens, and sequence variation in the gene may alter bladder cancer susceptibility. To examine the association between GSTP1Ile 105Val and bladder cancer, the authors undertook a meta- and pooled analysis. Summary crude and adjusted odds ratios and corresponding 95% confidence intervals were pooled by using a random-effects model. In the meta-analysis (16 studies, 4,273 cases and 5,081 controls), the unadjusted summary odds ratios for GSTP1 Ile/Val and Val/Val compared with GSTP1 Ile/Ile were 1.54 (95% confidence interval: 1.21, 1.99; p < 0.001) and 2.17 (95% confidence interval: 1.27, 3.71; p = 0.005). The association appeared to be the strongest in Asian countries. When the analysis was limited to European descendents (nine studies), the summary odds ratio decreased (odds ratio = 1.24, 95% confidence interval: 1.00, 1.52) (Q = 17.50; p = 0.02). All relevant data previously contributed to the International Study on Genetic Susceptibility to Environmental Carcinogens were pooled (eight studies, 1,305 cases and 1,558 controls). The summary odds ratios were similar to the ones from the meta-analysis. Case-only analyses did not detect an interaction between the GSTP1 genotype and smoking status (never/ever). GSTP1 Ile 105Val appears to be associated with a modest increase in the risk of bladder cancer. The work of W. A. Schulz was funded by the Deutsche Forschungsgemeinschaft. E. Taioli and G. Matullo are partially funded by ECNIS (Environmental Cancer Risk Nutrition and Individual Suspectibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (contract 513943).

BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.RESULTS: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.CONCLUSION: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.