ABSTRACT
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Carcinogens/toxicity , Occupational Exposure/adverse effects , Occupations/statistics & numerical data , Urinary Bladder Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Cadmium/adverse effects , Case-Control Studies , Humans , Italy/epidemiology , Male , Middle Aged , Neoplasm Grading , Occupational Exposure/statistics & numerical data , Risk Factors , Trichloroethylene/adverse effects , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/classificationABSTRACT
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 × 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.
Subject(s)
Calcium-Binding Proteins/genetics , Chromosomes, Human, Pair 20/genetics , Intercellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Urinary Bladder Neoplasms/genetics , White People/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Jagged-1 Protein , Male , Middle Aged , Polymorphism, Single Nucleotide , Serrate-Jagged ProteinsABSTRACT
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 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 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.
Subject(s)
Chromosomes, Human, Pair 5/chemistry , Gene Expression Regulation, Neoplastic , Genetic Loci , Membrane Proteins/genetics , Neoplasm Proteins/genetics , Neoplasms/genetics , Telomerase/genetics , Alleles , Computational Biology , DNA Methylation , Epigenesis, Genetic , Female , Gene Frequency , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Male , Neoplasms/pathology , Odds Ratio , Polymorphism, Single Nucleotide , RiskABSTRACT
PURPOSE: 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. METHODS: 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. RESULTS: 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 %). CONCLUSIONS: 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.
Subject(s)
Lung Neoplasms/etiology , Mandatory Reporting , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Occupational Medicine/methods , Adult , Aged , Female , Hospitals, Public , Humans , Italy/epidemiology , Lung Neoplasms/epidemiology , Male , Middle Aged , Occupational Diseases/epidemiology , Occupations , Surveys and QuestionnairesABSTRACT
BACKGROUND: Mental health problems are possible in migrant workers (MWs), who are mainly employed in dangerous jobs and face many barriers to prevention and care. OBJECTIVES: To outline current scientific evidence about psychosocial risk among MWs; to present data from clinical and field experiences. METHODS: Non-systematic literature review (PubMed, last 10 years); case series of 20 MWs, evaluated for mental and/or behavioural disorders at a public occupational health unit; applied field research, in enterprise contexts. RESULTS: A relatively low number of publications about psychosocial risk among MWs was found. Individual migrants may find the experience of migration to be stressful, with increased rates of depression and/or anxiety disorders. Data from clinical case series suggest that MWs from some ethnic groups, with a medium-high level of education, employed in metal or manufacturing industries, might have an increased risk of developing psychiatric disorders. Preliminary data from our field study seem to confirm that MWs, predominantly employed in unskilled/manual jobs and more prone to work overtime, tend to present higher prevalence of psychiatric disorders. CONCLUSIONS: There is a growing need to improve the scientific knowledge on migration, work, and mental health, as well as to promote workplace prevention of mental disorders in MWs. This can be achieved also by reducing structural barriers to mental wellbeing: in particular, occupational physicians should answer to MWs' mental health needs, contributing both to diagnosis and management of MWs' work-related psychiatric disorders.
Subject(s)
Mental Disorders/epidemiology , Mental Disorders/etiology , Mental Health , Transients and Migrants/psychology , Anxiety Disorders/epidemiology , Anxiety Disorders/etiology , Depressive Disorder/epidemiology , Depressive Disorder/etiology , Educational Status , Evidence-Based Medicine , Global Health , Health Services Needs and Demand , Humans , Italy/epidemiology , Mental Disorders/prevention & control , Mental Health Services , Prevalence , Risk Assessment , Risk Factors , Transients and Migrants/statistics & numerical dataABSTRACT
Fitness for work (FFW) is the final task of both risk assessment and health surveillance, aimed at protecting workers' health and working capacity. There are numerous specific concerns regarding health care workers. In particular: i) the frequent difficulty in determining at pre-employment/pre-placement examinations the specific task that the individual worker will perform; ii) the prevalence of female workers and the contemporary presence of numerous occupational risk factors that are a potential cause of harmful effects on women's reproductive health; iii) the progressive aging of the staff especially nurses; iv) the risk to third parties, with particular reference to the issues of biological risk and substance abuse, also in relation to shift work, fatigue and occupational stress; v) the increasing number of immigrant workers among support staff In such cases the occupational physician, respecting both ethical principles and regulations and with an appropriate balance between scientific evidence and the precautionary principle, should express a FFW judgment that allows both the adaptation of work to the worker and vice versa, as recommended by the World Health Organization (WHO) and the International Commission on Occupational Health (ICOH). Proper FFW judgment also permits the expected benefits to be achieved, not only for the workers but also for employers, companies and society.
Subject(s)
Health Personnel , Occupational Health , Work Capacity Evaluation , Age Factors , Female , Humans , Italy , Male , Occupational Health/ethics , Occupational Health/standards , Quality of Health Care , Risk AssessmentABSTRACT
PURPOSE: 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). METHODS: 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. RESULTS: In 1997-2009, 556 and 97 OI occurred in A and B, accounting for 11,597 and 2,567 LW, respectively. A significant (P < 0.01) decrease in OI incidence (-57% in A and -51% in B) and frequency (-56% in A and -46% in B) was shown. ITS analysis displayed a significant (P < 0.01) long-term decreasing trend for incidence (-0.29), frequency (-0.35) and severity (-0.55) rates in foundry B. Upper and lower extremity, eye, hand and head injuries were reduced. HS allowed focused human factor and fitness for work evaluation. Positive changes in safety culture and procedures were obtained. CONCLUSIONS: The intervention showed effectiveness in reducing OI rates and in improving quantitative and qualitative outcomes in two representative foundries. Challenges and limitations of interventions to assess effectiveness in preventing OI were evaluated and solutions applied.
Subject(s)
Accident Prevention/methods , Accidents, Occupational/prevention & control , Metallurgy , Occupational Injuries/prevention & control , Safety Management/methods , Adult , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Models, Statistical , Occupational Health Services , Occupational Injuries/epidemiology , Occupational Injuries/etiology , Time Factors , Young AdultABSTRACT
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 from <1/month to >3 times/week (P = 0.008). The case-only analysis showed an interaction between -2467T/delT and tobacco smoking >25 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.
Subject(s)
Cytochrome P-450 CYP1A2/genetics , Occupational Exposure/adverse effects , Polycyclic Aromatic Hydrocarbons/adverse effects , Polymorphism, Single Nucleotide , Smoking/adverse effects , Urinary Bladder Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Coffee/adverse effects , Humans , Italy , Male , Middle Aged , Occupational Exposure/statistics & numerical data , Odds Ratio , Prevalence , Promoter Regions, Genetic/genetics , Risk Factors , Smoking/epidemiology , Urinary Bladder Neoplasms/epidemiology , Young AdultABSTRACT
BACKGROUND: It is estimated that in Italy there are 4 million migrant workers, accounting for about 10 percent of the total workforce. They contribute to national economic development but they are also heavily involved in the so-called "3D jobs" (dangerous, dirty and demanding/degrading). OBJECTIVES: To draw occupational physicians' (OP) attention to the necessity of dealing with occupational health and safety problems related to migrant workers, highlighting his/her role and opportunities, in order to guarantee access to health services and prevent occupational health inequalities. METHODS: The available data on occupational diseases and accidents among migrant workers are discussed, as well as conditions of individual susceptibility; as an example, data are commented obtained in many years of health surveillance in a foundry. RESULTS: Migrant workers may suffer from occupational health inequalities. The OP, by means of focused risk assessment, health surveillance, fitness for work and health promotion, can substantially improve migrant workers' health. In fact, data from our experience showed how a migrant workforce may be well characterized and also represent an opportunity, instead of being a "risk factor". CONCLUSIONS: Within the framework of needs for further methodological and applied research, the OP can play a proactive role in workplaces, aimed at real integration of migrant workers, with overall benefits for workers, enterprises and society.
Subject(s)
Emigration and Immigration , Occupational Health , Occupational Medicine , Work , HumansABSTRACT
BACKGROUND: There is a lack of field studies aimed at reducing occupational injuries (OI), particularly in foundries. OBJECTIVES: To evaluate effectiveness of multidisciplinary intervention in foundries. METHODS: The study was carried out in two foundries (cast-iron=A, non-ferrous=B). Since 1999-2000, a multidisciplinary intervention was developed, by a team managed by the occupational physician, including safety personnel and workers' representatives. Interventions regarded maintenance, protective equipment, procedures, training, health surveillance (HS), fitness for work, first aid. The desired outcome was a reduction in injury rates. RESULTS: In foundries A and B, respectively 522 and 90 OI occurred in 1997-2007, accounting for 10,500 and 2,300 lost work days. Statistical analysis showed a significant decrease in incidence and frequency in both foundries. HS allowed for human factor and fitness for work evaluation, return-to-work management. Safety culture, behaviour and procedures positively changed. CONCLUSIONS: The study was effective in reducing OI rates and improving a number of secondary outcomes. The same intervention, taking into account Evidence Based Prevention, is ongoing in about 50 foundries.
Subject(s)
Accident Prevention/methods , Accidents, Occupational/prevention & control , Inservice Training , Metallurgy , Accidents, Occupational/statistics & numerical data , Evidence-Based Medicine , Humans , Incidence , Interdisciplinary Communication , Italy/epidemiology , Organizational Culture , Outcome Assessment, Health Care , Program Evaluation , Safety Management/organization & administration , Work Capacity Evaluation , WorkplaceABSTRACT
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' health needs.
Subject(s)
Occupational Diseases/epidemiology , Transients and Migrants/statistics & numerical data , Adolescent , Adult , Asthma/epidemiology , Dermatitis, Contact/epidemiology , Female , Hearing Loss, Noise-Induced/epidemiology , Hospitals, Public , Humans , Industry , Italy/epidemiology , Male , Mental Disorders/epidemiology , Middle Aged , Musculoskeletal Diseases/epidemiology , Neoplasms/epidemiology , Occupational Health , Occupations , Prevalence , Socioeconomic Factors , Young AdultABSTRACT
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.
Subject(s)
Emigrants and Immigrants , Occupational Health , Adult , Female , Health Status , Humans , Italy/epidemiology , Male , Mental Health , Prevalence , Risk Factors , Spain/epidemiology , WorkplaceABSTRACT
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 "ValVal" 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.
Subject(s)
Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/genetics , Occupational Diseases/chemically induced , Occupational Diseases/epidemiology , Occupational Exposure/adverse effects , Polymorphism, Genetic , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/genetics , Adult , Aged , Air Pollutants/adverse effects , Air Pollutants/analysis , Amines/adverse effects , Disease Progression , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Occupational Diseases/genetics , Occupational Exposure/statistics & numerical data , Polycyclic Aromatic Hydrocarbons/adverse effects , Risk Factors , Urinary Bladder Neoplasms/chemically inducedABSTRACT
INTRODUCTION: Occupational injuries are a relevant research and practical issue. However, intervention studies evaluating the effectiveness of workplace injury prevention programs are seldom performed. METHOD: 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. RESULTS: 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 (p<0.001). Sector-specific benchmarks for all injury rates were developed separately for ferrous and non-ferrous foundries. CONCLUSIONS: 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.
Subject(s)
Metallurgy , Occupational Health/statistics & numerical data , Occupational Injuries/prevention & control , Safety Management/methods , Accidents, Occupational/prevention & control , Humans , ItalyABSTRACT
BACKGROUND: No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines. METHODS: Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; the area under the curve was used to evaluate discriminatory ability of models. RESULTS: Area under the curve was 0.93 for the full model (including age, smoking and coffee habits, DNA adducts, 12 genotypes) and 0.86 for the short model (including smoking, DNA adducts, 3 genotypes). Using the "best cut-off" of predicted probability of a positive outcome, percentage of cases correctly classified was 92% (full model) against 75% (short model). Cancers classified as "positive outcome" are those to be referred for evaluation by an occupational physician for etiological diagnosis; these patients were 28 (full model) or 60 (short model). Using 3 genotypes instead of 12 can double the number of patients with suspect of aromatic amine related cancer, thus increasing costs of etiologic appraisal. CONCLUSIONS: Integrating clinical, laboratory and genetic factors, we developed the first etiologic prediction model for aromatic amine related bladder cancer. Discriminatory ability was excellent, particularly for the full model, allowing individualized predictions. Validation of our model in external populations is essential for practical use in the clinical setting.
ABSTRACT
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.
Subject(s)
Gene-Environment Interaction , Genetic Predisposition to Disease , Protein Structural Elements/genetics , Risk Assessment/statistics & numerical data , Telomere/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/physiopathology , Adult , Aged , Aged, 80 and over , Environmental Exposure/adverse effects , Humans , Male , Middle Aged , Occupational Exposure/adverse effects , Phenotype , Polymorphism, Genetic , Risk FactorsABSTRACT
BACKGROUND: About 15% of lung cancers (LC) might be attributable to occupation. However, clinical practice shows that LC percentage for which occupational aetiology is recognized is lower than expected. OBJECTIVES: To address the role of Occupational Physicians (OP) in systematic search and aetiological diagnosis of LC. METHODS: The search was carried out at a university hospital in Brescia, northern Italy, a highly industrialized area with many workers potentially exposed to occupational lung carcinogens. Through short occupational history forms, physicians of various departments refer all new cases of primary LC to OP When occupational exposure to lung carcinogens is presumed, the OP evaluates the case at the occupational health clinic and sends clinical reports to notifying physicians, containing aetiological diagnosis and indications for medico-legal obligations. RESULTS: Before 1998, few cases were referred to the OP and even less were compensated. The search yielded 1502 LC; after screening, full occupational health evaluation was performed in 693 cases: occupational aetiology was recognized in 182 (26%). Risk factors were silica, asbestos, polycyclic aromatic hydrocarbons, truck driving, painting, road paving; many workers were exposed to multiple carcinogens. 48 cases were compensated, many others are under litigation. CONCLUSIONS: A systematic LC search made it possible to: reach an aetiological diagnosis and reduce the gap between expected LC and those reported/compensated; inform health authorities and undertake preventive action in workplaces; detect sentinel events; provide epidemiological data at community level; promote cooperation among health professionals (oncologists, surgeons, pneumologists, general practitioners, plant OP); increase teaching opportunities for medical students, those taking a specialisation course in occupational health; provide counselling and expert opinions for individual subjects, trade unions, employers, law courts.
Subject(s)
Lung Neoplasms/diagnosis , Adult , Aged , Female , Humans , Lung Neoplasms/etiology , Male , Middle Aged , Occupational Diseases , Occupational Medicine , Physician's RoleABSTRACT
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.
Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Neoplasms/genetics , Adult , Aged , Asian People/genetics , Asian People/statistics & numerical data , Bone Neoplasms/genetics , Female , Humans , Kidney Neoplasms/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Lung Neoplasms/etiology , Lung Neoplasms/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Male , Middle Aged , Neoplasms/etiology , Osteosarcoma/genetics , Polymorphism, Single Nucleotide , Smoking/adverse effects , Testicular Neoplasms/genetics , Tissue Array Analysis , Urinary Bladder Neoplasms/etiology , Urinary Bladder Neoplasms/genetics , White People/genetics , White People/statistics & numerical dataABSTRACT
DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs) mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC) risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM) analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 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). No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (pâ=â0.028), whereas XRCC1 Arg 399 (p<0.006) was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001), coffee (p<0.001), cumulative AAs exposure (pâ=â0.041) and MnSOD (pâ=â0.009) and a decreased risk by MPO (p<0.008) were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different critical life stages.
Subject(s)
DNA Adducts/analysis , Models, Statistical , Polymorphism, Genetic , Urinary Bladder Neoplasms/pathology , Adult , Aged , Benzylamines/adverse effects , Case-Control Studies , Coffee/adverse effects , DNA Adducts/biosynthesis , DNA-Binding Proteins/genetics , Gene Expression , Gene-Environment Interaction , Humans , Leukocytes, Mononuclear/chemistry , Male , Middle Aged , Occupational Exposure/adverse effects , Peroxidase/genetics , Polycyclic Aromatic Hydrocarbons/adverse effects , Risk Factors , Smoking/adverse effects , Superoxide Dismutase/genetics , Urinary Bladder Neoplasms/etiology , Urinary Bladder Neoplasms/genetics , X-ray Repair Cross Complementing Protein 1ABSTRACT
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<0.001) whereas SWs showed no differences between the two subperiods, suggesting a possible occurrence of cross-protective immunity related to previous swH1N1 infections. These data underline the importance of risk assessment and occupational health surveillance activities aimed at early detection and control of SIVs with pandemic potential in humans.