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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.

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 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.

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.

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.

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.

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)).

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.

International audience; OBJECTIVE: A recent study suggested that risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes. We pooled primary data from 14 case-control studies of bladder cancer from Europe and North America and evaluated differences in risk of smoking by gender. METHODS: The pooled analysis included 8316 cases (21% women) and 17,406 controls (28% women) aged 30-79 years. Odds ratios (ORs) and 95% confidence intervals (95% CI) for smoking were adjusted for age and study. Exposure-response was evaluated in a stratified analysis by gender and by generalized additive models. RESULTS: The odds ratios for current smokers compared to nonsmokers were 3.9 (95% CI 3.5-4.3) for males and 3.6 (3.1-4.1) for females. In 11 out of 14 studies, ORs were slightly higher in men. ORs for current smoking were similar for men (OR = 3.4) and women (OR = 3.7) in North America, while in Europe men (OR = 5.3) had higher ORs than women (OR = 3.9). ORs increased with duration and intensity in both genders and the exposure-response patterns were remarkably similar between genders. CONCLUSION: These results do not support the hypothesis that women have a higher relative risk of smoking-related bladder cancer than men.

Background: Exposure to disinfection byproducts in drinking water has been associated with an increased risk of bladder cancer. We pooled the primary data from 6 case-control studies of bladder cancer that used trihalomethanes as a marker of disinfection byproducts. Methods: Two studies were included from the United States and one each from Canada, France, Italy, and Finland. Inclusion criteria were availability of detailed data on trihalomethane exposure and individual water consumption. The analysis included 2806 cases and 5254 controls, all of whom had measures of known exposure for at least 70% of the exposure window of 40 years before the interview. Cumulative exposure to trihalomethanes was estimated by combining individual year-by-year average trihalomethane level and daily tap water consumption. Results: There was an adjusted odds ratio (OR) of 1.24 in men exposed to an average of more than 1 g/L (ppb) trihalomethanes compared with those who had lower or no exposure (95% confidence interval [CI] 1.09 ‐1.41). Estimated relative risks increased with increasing exposure, with an OR of 1.44 (1.20 ‐1.73) for exposure higher than 50 g/L (ppb). Similar results were found with other indices of trihalomethane exposure. Among women, trihalomethane exposure was not associated with bladder cancer risk (0.95; 0.76 ‐1.20). Conclusions: These findings strengthen the hypothesis that the risk of bladder cancer is increased with long-term exposure to disinfection byproducts at levels currently observed in many industrialized countries. (Epidemiology 2004;15: 357‐367)

The authors investigated the dose-effect relation between alcohol drinking and hepatocellular carcinoma (HCC) in men and women separately, also considering hepatitis B and hepatitis C virus infections. They enrolled 464 subjects (380 men) with a first diagnosis of HCC as cases and 824 subjects (686 men) unaffected by hepatic diseases as controls; all were hospitalized in Brescia, northern Italy, in 1995-2000. Spline regression models showed a steady linear increase in the odds ratio of HCC for increasing alcohol intake, for values of >60 g of ethanol per day, with no substantial differences between men and women. Duration of drinking and age at start had no effect on the odds ratio when alcohol intake was considered. Former drinkers who had stopped 1-10 years previously had a higher risk of HCC than current drinkers did. The effect of alcohol drinking was evident even in the absence of hepatitis B or hepatitis C virus infection. In addition, a synergism between alcohol drinking and either infection was found, with approximately a twofold increase in the odds ratio for each hepatitis virus infection for drinkers of >60 g per day.

Summary A 60-year-old male subject who worked as a movie projectionist and who was exposed for 12 years to rare earths (RE) containing dusts from cored arc light carbon electrodes was investigated. Chest X-ray films and pulmonary function tests showed an interstitial lung disease, emphysema and a severe obstructive impairment with marked decrease of carbon monoxide diffusion capacity. The histological examination of a transbronchial biopsy confirmed the diffuse interstitial lung fibrosis. Neutron activation analysis (NAA) of the biopsy showed concentrations of cerium (Ce), lanthanum (La), neodimium (Nd), samarium (Sm), terbium (Tb) and ytterbium (Yb) which were high compared to the corresponding elements in the transbronchial biopsies of 5 unexposed subjects as a control group. Thorium (Th) (which is generally present as an impurity of the RE compounds) was also determined in order to estimate the radiation dose in the lung of the worker. On the basis of the clinical observations, of the analytical results by neutron activation analysis of RE and of the presence of Th in the transbronchial biopsy, as well as of the differential diagnosis, which tended to exclude other occupational or non-occupational lung diseases, a relation between the observed interstitial lung fibrosis and occupational exposure to RE is highly probable.

Transitional-cell carcinoma is the dominant histological type of malignant tumors of the urinary bladder. There is limited information on risk factors for non-transitional-cell carcinoma (NTCC) of the bladder. We used data from 9 case-control studies on bladder cancer from 6 European countries to examine the association between NTCC, tobacco smoking and occupation. Information on 146 cases diagnosed with NTCC were matched by age, gender and study center to 727 non-cancer population or hospital controls and also with 722 transitional-cell-bladder-cancer controls. Lifetime smoking and occupational history were evaluated. A statistically significant excess risk for NTCC was observed for current smoking [odds ratio (OR) = 3.61, 95% confidence interval (CI) 2.08-6.28]. The risk increased with higher tobacco consumption (OR for highest tertile of pack-years = 7.01, 95% CI 3.60-13.66). The risks were higher for squamous-cell carcinomas than for other types of NTCC. Among major occupational groups, a significant excess risk was seen for field-crop and vegetable-farm workers (OR = 2.06, 95% CI 1.03-4.10). These results indicate that NTCC of the bladder is associated with smoking and specific occupations. The risk pattern seems to differ, in part, from that observed for transitional-cell carcinoma of the bladder.

OBJECTIVE: To critically review the literature on male reproductive toxicity of lead in animals and humans. METHODS: A systematic literature search identified a total of 32 experimental studies in animals and 22 epidemiological studies, one case report on humans and five review articles or documents. The studies were evaluated by paying attention mainly to sample size, study design, exposure, and dose characterisation, analytical method standardisation, and quality assurance. RESULTS: Several studies on rats and other rodents indicated that blood lead concentrations > 30-40 micrograms/dl were associated with impairment of spermatogenesis and reduced concentrations of androgens. However, other animal studies, mainly about histopathological, spermatozoal, and hormonal end points, indicated that certain species and strains were quite resistant to the reproductive toxicity of lead and that different testicular lead concentrations could account for these differences. The human studies focused mainly on semen quality, endocrine function, and birth rates in occupationally exposed subjects, and showed that exposure to concentrations of inorganic lead > 40 micrograms/dl in blood impaired male reproductive function by reducing sperm count, volume, and density, or changing sperm motility and morphology. No relevant effects were detected on endocrine profile. CONCLUSION: Several factors make it difficult to extrapolate the animal data to the human situation. The difficulties are mainly due to differences between species in reproductive end points and to the level of exposure. Concentrations of blood lead > 40 micrograms/dl seemed to be associated with a decrease in sperm count, volume, motility, and morphological alterations and a possible modest effect on endocrine profile. Dose-response relation, in particular at a threshold level, is poorly understood, and site, mode, or mechanism of action are unknown. Also, the effects were not always the same or associated in the same on sperm count and concentration. Some methodological issues and indications for future studies are discussed.

Chelating agents have long been used in the pharmacological treatment of lead poisoning, whose management is still a problem, particularly in developing countries. This article reviews the pharmacological properties of dimercaprole, peniclliamine. CaNa2EDTA and dimercaprosuccinic acid, examines their indications, contraindications and side effects and discusses the possible use of each drug in occupational Pb poisoning. Proposals are also presented for the treatment and follow-up of subjects with signs and symptoms of poisoning and of subjects with low-moderate Pb absorption. CaNa2EDTA seems to be the most reliable and safer chelating agent nowadays available and with a wider spectrum of action. DMSA seems to be promising in the treatment of occupational Pb poisoning. Even though there is no doubt that chelation therapy has significantly contributed to reduce mortality and morbidity from occupational Pb poisoning, the efficacy of this treatment in subjects with subtle neurological or renal damage has not yet been studied properly.

We evaluated the chelation test in 38 subjects exposed to lead or with suspected lead exposure, comparing the values of lead excretion at the 3rd h (PbU EDTA/3-h) and at the 24th h (PbU EDTA/24-h) after EDTA administration. Good correlation exists between PbU EDTA/3-h and PbU EDTA/24-h (r = .86) and between them and the main biological indicators of dose and effect of lead. When a second chelation test was performed in 15 subjects, a slightly better r coefficient (.93) was observed between the two tests, without reaching statistical significance. It seems difficult, in terms of the type of exposure that we considered, to use the 3-h test, on an individual basis, to predict the PbU EDTA/24-h values.

Urinary mutagenic activity detected by the bacterial fluctuation assay, using Salmonella typhimurium TA98 and Escherichia coli WP2 uvr A with and without metabolic activation (S9 mix), was studied in a group of 21 workers exposed to inorganic lead and a control group of 22 non-occupationally exposed subjects. Occupational exposure to inorganic lead had no effect on urinary mutagenicity in the strains considered, with or without metabolic activation. In smokers (exposed and non-exposed), urinary mutagenic activity appeared to increase compared to non-smokers (exposed and non-exposed), only with Salmonella typhimurium TA98 in the presence of S9 mix.