Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study.

BACKGROUND: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS: 47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION: Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

Incidence of mesothelioma in young people and causal exposure to asbestos in the Italian national mesothelioma registry (ReNaM).

INTRODUCTION: The epidemiological surveillance of mesothelioma incidence is a crucial key for investigating the occupational and environmental sources of asbestos exposure. The median age at diagnosis is generally high, according to the long latency of the disease. The purposes of this study are to analyse the incidence of mesothelioma in young people and to evaluate the modalities of asbestos exposure. METHODS: Incident malignant mesothelioma (MM) cases in the period 1993-2018 were retrieved from Italian national mesothelioma registry and analysed for gender, incidence period, morphology and exposure. Age-standardised rates have been calculated and the multiple correspondence analysis has been performed. The association between age and asbestos exposure has been tested by χ2 test. RESULTS: From 1993 to 2018, 30 828 incident MM cases have been collected and 1278 (4.1%) presented diagnosis at early age (≤50 years). There is a substantial association between age at diagnosis and the type of asbestos exposure and a significantly lower frequency of cases with occupational exposure to asbestos (497 cases vs 701 expected) in young people has been documented. Paraoccupational and environmental exposure to asbestos have been found more frequent in young MM cases (85 and 93 observed cases vs 52 and 44 expected cases, respectively). CONCLUSIONS: Mesothelioma incidence surveillance at population level and the anamnestic individual research of asbestos exposure is a fundamental tool for monitoring asbestos exposure health effects, supporting the exposure risks prevention policies. Clusters of mesothelioma incident cases in young people are a significant signal of a potential non-occupational exposure to asbestos.

Night shift work and lymphoma: results from an Italian multicentre case-control study.

BACKGROUND: Night shift work can disrupt circadian rhythm and cause chronic sleep deprivation, which might increase the risk of lymphoma through immunosuppression and oxidative stress. MATERIAL AND METHODS: We investigated the association between night shift work and risk of lymphoma subtypes in 867 incident cases and 774 controls, who participated in a multicentre Italian study between 2011 and 2017. Based on questionnaire information, occupational experts assessed the lifetime probability of night shift work, the total number of night shifts and years of night shift work among study participants. OR and 95% CI for lymphoma and its major subtypes associated with night shift work was calculated with logistic regression, adjusting by age, gender, education, study area, marital status and family history of haemolymphatic cancer. RESULTS: Ever working night shifts was associated with an increase in the risk of chronic lymphocytic leukaemia (CLL) (OR 1.9, 95% CI 1.14 to 3.32), which was highest after a 15-34 years latency. However, there was not a linear increase in risk by probability of exposure, years of night shift work, nor lifetime number of night shifts whether under rotating or permanent work schedules. Risk of lymphoma overall, B cell lymphoma (BCL), its major subtypes other than CLL, and other less prevalent BCL subtypes combined did not show an association. CONCLUSIONS: We found conflicting evidence of an association between night shift work and the risk of CLL. We did not observe an association with other lymphoma subtypes.

Herbicide use in farming and other jobs in relation to non-Hodgkin's lymphoma (NHL) risk.

OBJECTIVES: Given mixed evidence for carcinogenicity of current-use herbicides, we studied the relationship between occupational herbicide use and risk of non-Hodgkin's lymphoma (NHL) in a large, pooled study. METHODS: We pooled data from 10 case-control studies participating in the International Lymphoma Epidemiology Consortium, including 9229 cases and 9626 controls from North America, the European Union and Australia. Herbicide use was coded from self-report or by expert assessment in the individual studies, for herbicide groups (eg, phenoxy herbicides) and active ingredients (eg, 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate). The association between each herbicide and NHL risk was estimated using logistic regression to produce ORs and 95% CIs, with adjustment for sociodemographic factors, farming and other pesticides. RESULTS: We found no substantial association of all NHL risk with ever-use of any herbicide (OR=1.10, 95% CI: 0.94 to 1.29), nor with herbicide groups or active ingredients. Elevations in risk were observed for NHL subtypes with longer duration of phenoxy herbicide use, such as for any phenoxy herbicide with multiple myeloma (>25.5 years, OR=1.78, 95% CI: 0.74 to 4.27), 2,4-D with diffuse large B-cell lymphoma (>25.5 years, OR=1.47, 95% CI: 0.67 to 3.21) and other (non-2,4-D) phenoxy herbicides with T-cell lymphoma (>6 years, lagged 10 years, OR=3.24, 95% CI: 1.03 to 10.2). An association between glyphosate and follicular lymphoma (lagged 10 years: OR=1.48, 95% CI: 0.98 to 2.25) was fairly consistent across analyses. CONCLUSIONS: Most of the herbicides examined were not associated with NHL risk. However, associations of phenoxy herbicides and glyphosate with particular NHL subtypes underscore the importance of estimating subtype-specific risks.

[A suspect cluster of childhood cancer in Valle di Ledro (Province of Trento, Northern Italy). Epidemiological evaluation, risk management, and communication activities, 2018-2020]. / Un sospetto cluster di tumori infantili in Valle di Ledro (provincia di Trento). Valutazione epidemiologica e attività di comunicazione e gestione del rischio. Anni 2018-2020.

BACKGROUND: leukaemia is the most prevalent form of childhood cancer, an overall rare condition in childhood. Even few cases occurring in a small community can cause considerable apprehension among the population. From 2014 to 2017, 4 cases of childhood cancer occurred in Valle di Ledro, a municipality of 5,300 inhabitants in Province of Trento (Northern Italy), and a group of concerned citizens asked provincial health authorities for an investigation. OBJECTIVES: to address the community's health needs by verifying the hypothesis of a cluster of childhood cancer and through effective risk communication activities. DESIGN: retrospective cohort analysis based on data from the Cancer registry of the Autonomous Province of Trento and data collected from hospital discharge records. The communication activities were carried out according to the recommendations published by Epidemiologia&Prevenzione in 2016 in a Supplement "Childhood cancers, risk factors and investigation models for the evaluation of spatio-temporal clusters". SETTING AND PARTICIPANTS: Valle di Ledro, a municipality of 5,300 inhabitants in the Province of Trento. The participants in risk communication process were: city council; grassroot committee of concerned parents; health workforce of different services (epidemiology, cancer registry, public health; environmental health; primary health care; personnel of the Environmental Protection Agency; journalists; general population. The participants in the statistical analyses were: children of 0-14 years of age who were diagnosed a cancer from 1998 to 2014 in the Province of Trento (N. 212); leukaemia (N. 84) and acute lymphoblastic leukaemia (N. 66) incident cases in the period 1998-2017 in Trento province. MAIN OUTCOME MEASURES: verification of the presence of a cluster of childhood cancers; degree of consensus and collaboration of the different community stakeholders to the survey procedures and acceptance of the final results; atmosphere in public assemblies and feedback in the local press. RESULTS: a total of 212 incident cancer cases in children 0-14 years have been registred in Province of Trento from 1998 to 2014, leukaemia in 35% (N. 74) cases. From 2015 to 2017, another 10 cases of leukaemia occurred, for a total of 84 cases of leukaemia from 1998 to 2017. In the years from 1998 to 2017, in Valle di Ledro, taking the Italian population as reference group, the standardized incidence ratios (SIRs) were the following: cancer, all types 1,47 (IC95% 0,40-3,76); leukaemia 3,39 (IC95% 0,70-9,90), LLA 2,81 (IC95% 0,34-10,16). No cluster emerged from the geographical analyses. From the very beginning of the risk management approach, a decision-making working group was set up applying a participatory approach. Group members included the city council and the local committee of concerned parents and experts from different services of the local health unit. Data analyses was delegated to a technical working group that reported back to the decision-making group. Members of the technical working group were supervised by external experts. Following this approach, it was possible to establish a climate of trust and credibility. The involvement of all stakeholders right from the start in a totally transparent process was a key element of success. CONCLUSIONS: the cluster hypothesis was rejected for both childhood cancer (all types) and leukaemia (all types and ALL). The implementation of the risk communication process recommended by the AIE guidelines was successful in establishing a climate of reciprocal trust that allowed to overcome inevitable moments of conflict in a productive manner. Thanks to this positive atmosphere, the communication of the results of the statistical analyses was effective in reassuring the population.

Occupational insecticide exposure and risk of non-Hodgkin lymphoma: A pooled case-control study from the InterLymph Consortium.

Evidence for the human health effects of pesticides is needed to inform risk assessment. We studied the relationship between occupational insecticide use and risk of non-Hodgkin lymphoma (NHL) by pooling data from nine case-control studies participating in the InterLymph Consortium, including 7909 cases and 8644 controls from North America, the European Union and Australia. Insecticide use was coded using self-report or expert assessment, for insecticide groups (eg, organophosphates, pyrethroids) and active ingredients (eg, malathion, permethrin). Associations with insecticides were estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CI) for all NHL and NHL subtypes, with adjustment for study site, demographic factors and use of other pesticides. Occupational insecticide use, overall, was not associated with risk of NHL. Use of organophosphate insecticides was associated with increased risk of all NHL and the subtype follicular lymphoma, and an association was found with diazinon, in particular (ever use: OR = 2.05, 95%CI: 1.24-3.37). The carbamate insecticide, carbaryl, was associated with risk of all NHL, and the strongest associations were found with T-cell NHL for ever-use (OR = 2.44, 95%CI: 1.13-5.28) and longer duration (>8 years vs never: OR = 2.90, 95%CI: 1.02-8.25). There was no association of NHL with other broad groups of insecticides, including organochlorines and pyrethroids, and some inverse associations were estimated in relation to historical DDT use. Our findings contribute to the totality of evidence available to help inform risk decisions by public health and regulatory agencies of importance given continued, widespread use of organophosphate and carbamate insecticides.

Exposure to drinking water trihalomethanes and nitrate and the risk of brain tumours in young people.

Brain tumours (BTs) are one of the most frequent tumour types in young people. We explored the association between tap water, exposure to trihalomethanes (THM) and nitrate and neuroepithelial BT risk in young people. Analysis of tap water consumption were based on 321 cases and 919 appendicitis controls (10-24 years old) from 6 of the 14 participating countries in the international MOBI-Kids case-control study (2010-2016). Available historical residential tap water concentrations of THMs and nitrate, available from 3 countries for 86 cases and 352 controls and 85 cases and 343 for nitrate, respectively, were modelled and combined with the study subjects' personal consumption patterns to estimate ingestion and residential exposure levels in the study population (both pre- and postnatal). The mean age of participants was 16.6 years old and 56% were male. The highest levels and widest ranges for THMs were found in Spain (residential and ingested) and Italy and in Korea for nitrate. There was no association between BT and the amount of tap water consumed and the showering/bathing frequency. Odds Ratios (ORs) for BT in relation to both pre- and postnatal residential and ingestion levels of THMs were systematically below 1 (OR = 0.37 (0.08-1.73)) for postnatal average residential THMs higher than 66 µg/L. For nitrate, all ORs were above 1 (OR = 1.80 (0.91-3.55)) for postnatal average residential nitrate levels higher than 8.5 mg/L, with a suggestion of a trend of increased risk of neuroepithelial BTs with increasing residential nitrate levels in tap water, which appeared stronger in early in life. This, to our knowledge, is the first study on this topic in young people. Further research is required to clarify the observed associations.

Occupational exposure to glyphosate and risk of lymphoma:results of an Italian multicenter case-control study.

BACKGROUND: The International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy. METHODS: The Italian Gene-Environment Interactions in Lymphoma Etiology (ItGxE) study took place in 2011-17 in six Italian centres. Overall, 867 incident lymphoma cases and 774 controls participated in the study. Based on detailed questionnaire information, occupational experts classified duration, confidence, frequency, and intensity of exposure to glyphosate for each study subject. Using unconditional regression analysis, we modelled risk of major lymphoma subtypes associated with exposure to glyphosate adjusted by age, gender, education, and study centre. RESULTS: Very few study subjects (2.2%) were classified as ever exposed to glyphosate. Risk of follicular lymphoma (FL) was elevated 7-fold in subjects classified as ever exposed to glyphosate with medium-high confidence, 4.5-fold in association with medium-high cumulative exposure level, 12-fold with medium-high exposure intensity, and 6-fold with exposure for 10 days or more per year. Significant upward trends were detected with all the exposure metrics, but duration. The overall p-value for an upward trend with four independent metrics was 1.88 × 10- 4. There was no association with risk of lymphoma (any subtype), Non Hodgkin Lymphoma, B-cell lymphoma, or the major lymphoma subtypes other than FL. CONCLUSIONS: Our findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen.

[Mortality and cancer risk in agricultural nursery workers: a cohort study in Tuscany Region (Central Italy)]. / Mortalità e rischio cancerogeno nei florovivaisti: uno studio di coorte in Toscana.

OBJECTIVES: to follow-up mortality of agricultural nursery workers of the province of Pistoia (Tuscany Region, Central Italy). DESIGN: the cohort of nursery workers of the Pistoia province was assembled from two sources: subjects who obtained a pesticide license (PAT) and subjects who had been working in agricultural nursery, based on the 2003 regional census (LIF). Vital status and causes of deaths were ascertained through the official records of the municipalities and the Tuscany Mortality Register. The follow-up period for PAT cohort was from 01.01.1984 to 31.12.2015 and for LIF cohort was from 01.01.2003 al 31.12.2015. SETTING AND PARTICIPANTS: the total cohort included 2,732 males and 326 females: the PAT cohort included 1,602 males and 106 females, and the LIF cohort included 1,130 males and 220 females MAIN OUTCOME MEASURES: general and cause-specific Standardized Mortality Ratios (SMRs) and 95% confidence intervals were calculated for the entire cohort and for the PAT and LIF sub-cohorts. Expected deaths by age and gender for each cause of death were obtained from applying the respective rates in the Tuscan population. RESULTS: overall mortality was lower than expected, with notable deficits for all cancers and some specific causes in both genders. Among males, increased SMRs were observed for pancreas (17 observed cases: SMR 129; CI95% 75-207), prostate (22 cases: SMR 121; CI95% 76-183), bladder (18 cases: SMR 139; CI95% 83-220) cancer, and also for multiple myeloma (5 cases: SMR 120; CI95% 39-281). Among females, increased SMR for cancer of digestive system and peritoneum was observed (3 cases: SMR 152; IC95% 31-445). The analyses by calendar period also shown excess for cancers of the genital and urinary system and the lymphohematopoietic system. CONCLUSIONS: although overall deficits for all causes and all cancer were observed, there were notable exceptions for some specific cancer causes, that might be related to pesticides exposure.

Childhood infectious diseases and risk of non-Hodgkin's lymphoma according to the WHO classification: A reanalysis of the Italian multicenter case-control study.

Since 1960, incidence of non-Hodgkin's lymphoma (NHL) has been increasing in most industrialized countries, but causes of this trend remain unclear. A role of the decreased exposure to infectious agents during childhood has been proposed. Our study evaluates the association between common childhood infectious diseases and the risk of NHL and its major subtypes by a reanalysis of the Italian multicenter case-control study. After exclusion of next-of-kin interviews, 1,193 cases, diagnosed between 1990 and 1993, and 1,708 population-based controls were included in the analyses. OR estimates were obtained by logistic regression, adjusting for gender, age, residence area, education, smoking habit and exposure to radiations, pesticides and aromatic hydrocarbons. Among B-cell lymphomas (n = 1,102) an inverse association was observed for rubella (OR = 0.80, 95% CI: 0.65-0.99), pertussis (OR = 0.74, 95% CI: 0.62-0.88) and any infection (OR = 0.75, 95% CI: 0.61-0.93). A negative trend by number of infections was observed, which was more evident among mature B-cell lymphoma (OR = 0.66 for three infections or more, 95% CI: 0.48-0.90). Our results indicate a potential protective role of common childhood infections in the etiology of B-cell NHL.

Clinical presentation of young people (10-24 years old) with brain tumors: results from the international MOBI-Kids study.

INTRODUCTION: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). METHODS: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location. RESULTS: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays. CONCLUSIONS: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis.

Wood dust and urinary 15-F2t isoprostane in Italian industry workers.

Wood dust is one of the most common occupational exposures, with about 3.6 million of workers in the wood industry in Europe. Wood particles can deposit in the nose and the respiratory tract and cause adverse health effects. Occupational exposure to wood dust has been associated with malignant tumors of the nasal cavity and paranasal sinuses. The induction of oxidative stress and the generation of reactive oxygen species through activation of inflammatory cells could have a role in the carcinogenicity of respirable wood dust. Therefore, we conducted a cross-sectional study to evaluate the prevalence of urinary 15-F2t isoprostane (15-F2t-IsoP), a biomarker of oxidative stress and peroxidation of lipids, in 123 wood workers compared to 57 unexposed controls living in Tuscany region, Italy. 15-F2t-IsoP generation was measured by ELISA. The main result of the present study showed that a statistically significant excess of this biomarker occurred in the workers exposed to 1.48 mg/m3 of airborne wood dust with respect to the unexposed controls. The overall mean ratio (MR) between the workers exposed to wood dust and the controls was 1.36, 95% Confidence Interval (C.I.) 1.18-1.57, after correction for age and smoking habits. A significant increment of 15-F2t-IsoP (43%) was observed in the smokers as compared to the non-smokers. The urinary excretion of 15-F2t-IsoP was significantly associated with co-exposure to organic solvents, i.e., MR of 1.41, 95% C.I. 1.17-1.70, after adjustment for age and smoking habits. A 41% excess was observed in long-term wood workers, 95% C.I. 1.14-1.75. Multivariate regression analysis showed that the level of 15-F2t-IsoP was linearly correlated to the length of exposure, regression coefficient (ß) = 0.244 ±â€¯0.002 (SE). The overall increment by exposure group persisted after stratification for smoking habits. For instance, in smokers, a 53% excess was detected in the wood workers as compared to the controls, 95% C.I. 1.23-1.91. Our data support the hypothesis that oxidative stress and lipid peroxidation can have a role in the toxicity of wood dust F2-IsoP measure can be a tool for the evaluation of the effectiveness of targeted interventions aimed to reduce exposures to environmental carcinogens.

[Investigative model for the evaluation of spatio-temporal clusters of childhood cancers]. / Modelli di indagine per la valutazione di cluster spazio-temporali di tumori infantili.

This paper describes the conceptual framework and the critical issues of investigations of clusters of childhood cancers and defines an investigative model for the health authorities responsible for assessing a suspected cluster, taking into account the guidelines available and considering the most recent advances of the Geographical Information System and of the specific statistical methodology. Three main investigation phases are identified: the first consists in the preliminary study on the health of population living in the area where the cases are defined and aetiological hypotheses are formulated; the second is the cluster evaluation study using statistical methods assessing the spatial heterogeneity and collecting information about potential risk factors; the third is the analytical epidemiological study to test aetiological hypotheses suggested by the previous phases. The residential cohort approach is the most valid to date to assess long-term effects, and allows to reconstruct the lifetime residential history from the population registry. The researchers' decision on how detailed about a suspected cluster the investigation has to be needs to take into account both the level of alarm in the population and the limited resources available. The concern about a suspected cluster of cancer cases should always be addressed, even if this implies to acknowledge limits of research and uncertainty in results interpretation.

Gender Differences in Sinonasal Cancer Incidence: Data from the Italian Registry.

BACKGROUND: Although rare, sinonasal cancers (SNCs) have a high occupational attributable fraction. METHODS: We applied gender-based approaches to descriptive analyses, incidence, and patterns of exposures using the Italian National Sinonasal Cancer Registry (ReNaTuNS: Registro Nazionale Tumori Naso-Sinusali). RESULTS: The study included 2851 SNC patients. SNC was diagnosed more often in men (73%) than in women (27%). The most frequent morphology in men was intestinal-type adenocarcinoma (33%), whereas in women, it was squamous cell carcinoma (49%). Nasal cavities were predominant in both genders (50%), ethmoidal sinus in men (24%), and maxillary in women (24%). Incidence rates were 0.76 (per 100,000 person-years) in men and 0.24 in women and increased by age, more evidently in men, peaking over 75 years in both. Occupational exposures to wood and leather dusts were the most frequent (41% for men, 33% for women). Few exposures were extra-occupational or domestic. Unlikely exposure was relevant in women (57%). CONCLUSIONS: The surveillance of SNC cases through a registry that allows for the identification of and compensation for this occupational disease is important in Italy, where numerous workers are exposed to carcinogens for SNC, without even being aware. Considering the rarity of the disease, particularly among women, the ReNaTuNS can provide a method to analyze gender differences.

Aromatic DNA adducts and number of lung cancer risk alleles in Map-Ta-Phut Industrial Estate workers and nearby residents.

The Map-Ta-Phut Industrial Estate (MIE) in Rayong, Thailand, is the location of one of the largest industrial complexes in southeastern Asia. The MIE complex produces a mixture of air pollutants, including polycyclic aromatic hydrocarbons, compounds capable to induce the generation of DNA adducts. DNA adducts are considered to be a biomarker of carcinogen exposure; however, its production can be modulated by genetic susceptibility. Thus, we analysed the influence of EPHX1 His139Arg (A>G, rs2234922) and NQO1 Pro187Ser (C>T, rs1800566) involved in the metabolism of polycyclic aromatic hydrocarbons; MnSOD(2) Val16Ala (C>T, rs1799725) a gene that acts against the free radical generation; APE1/Ref-1 Asp148Glu (T>G, rs3136820) a gene involved in the repair of DNA, and in the control of cell-cycle and apoptosis on leucocyte DNA adducts in 77 MIE workers, 69 Map-Ta-Phut residents, and 50 rural controls, Rayong, Thailand. We searched for associations with the 'sum of at-risk alleles' by combining the variant alleles of EPHX1, NQO1 and MnSOD(2) together with the wild-type allele of APE1, since they appeared to influence lung cancer risk. Although our findings revealed significant associations between DNA adducts and the EPHX1 His139Arg and NQO1 Pro187Ser polymorphisms, the combination of at-risk alleles was found to affect DNA damage much stronger. DNA adducts were significantly increased in the individuals bearing 4 and ≥ 5 at-risk alleles [mean ratio (MR) = 1.55, 95% CI 1.10-2.18, P = 0.012, and MR = 2.11, 95% CI 1.27-3.51, P = 0.004, respectively)]. After correction for residence/employment categorisation, a significant increment was present in the MIE workers with ≥ 5 alleles (MR = 2.88, 95% CI 1.46-5.71, P = 0.003). Our data indicate relationships between the generation of DNA adducts and the enzymatic activities of EPHX and NQO1. The combination of unfavourable genetic variants seems to determine the individuals' susceptibility, rather than a single polymorphism.

Formaldehyde and Acetaldehyde Exposure in "Non-Traditional" Occupational Sectors: Bakeries and Pastry Producers.

INTRODUCTION: Formaldehyde, a colorless and highly irritating substance, causes cancer of the nasopharynx and leukemia. Furthermore, it is one of the environmental mutagens to which humans are most abundantly exposed. Acetaldehyde was recently classified as carcinogen class 1B and mutagen class 2 in Annex VI EC regulation. Occupational exposure to the two aldehydes occurs in a wide variety of occupations and industries. The aim of this study is to deepen exposure to the two aldehydes in the non-traditional productive sectors of bakeries and pastry producers. METHODS: The evaluation of exposure to formaldehyde and acetaldehyde was conducted in Italy in 2019, in specific tasks and positions of 11 bakeries and pastry producers (115 measures, of which 57.4% were in fixed positions and the rest were personal air sampling). The measurements were performed using Radiello© radial diffusion samplers. A logarithmic transformation of the data was performed, and the correlation between the two substances was calculated. Moreover, linear models considering the log-formaldehyde as the outcome and adjusting for log-acetaldehyde values were used. RESULTS: The study identified high levels of acetaldehyde and formaldehyde exposure in the monitored workplaces. Higher mean values were observed in the leavening phase (8.39 µg/m3 and 3.39 µg/m3 for log-transformed data acetaldehyde and formaldehyde, respectively). The adjusted univariate analyses show statistically significant factors for formaldehyde as the presence of yeast, the presence of type 1 flour, the use of barley, the use of fats, the type of production, the use of spelt, and the presence of type 0 flour. CONCLUSIONS: The measurements confirmed the release of formaldehyde and acetaldehyde in bakeries and pastry industries, especially in some phases of the work process, such as leavening.

Pleural mesothelioma risk in the construction industry: a case-control study in Italy, 2000-2018.

OBJECTIVES: Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers. DESIGN: Case-control study. SETTING: Cases from the National Mesothelioma Registry (2000-2018), controls from three previous case-control studies. METHODS: We selected male PM incident cases diagnosed in 2000-2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002-2004 and 2012-2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses. RESULTS: The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower. CONCLUSIONS: We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.

Parental occupational exposure to combustion products, metals, silica and asbestos and risk of childhood leukaemia: Findings from the Childhood Cancer and Leukaemia International Consortium (CLIC).

Parental occupational exposures around conception (father) or during pregnancy (mother) have been hypothesized as potential predisposing factors for childhood leukaemia. We investigated parental exposure to several known occupational carcinogens and childhood leukaemia risk. We conducted a pooled analysis using case-control data from four European countries (3362 childhood leukemia cases and 6268 controls). Parental occupational exposures to polycyclic aromatic hydrocarbons (PAH), diesel engine exhaust (DEE), chromium, nickel, crystalline silica, and asbestos were assessed by a general population job-exposure matrix. We estimated odd ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models for all childhood leukaemia combined, by leukaemia type (ALL and AML) and by ALL subtype (B-lineage and T-lineage). We found an association between high paternal occupational exposure to crystalline silica and childhood ALL (OR 2.20, CI 1.60-3.01) with increasing trend from no exposure to high exposure (P = <0.001), and also for AML (OR 2.03, CI 1.04-3.97; P for trend = 0.008). ORs were similar for B- and T-lineage ALL. For ALL, ORs were also slightly elevated with wide confidence intervals for high paternal occupational exposure to chromium (OR 1.23, CI 0.77-1.96), and DEE (OR 1.21, CI 0.82-1.77). No associations were observed for paternal exposures to nickel, PAH and asbestos. For maternal occupational exposure we found several slightly elevated odds ratios but mostly with very wide confidence intervals due to low numbers of exposed mothers. This is a first study suggesting an association between fathers' occupational exposure to crystalline silica and an increased risk of childhood leukaemia in their offspring. As this association was driven by certain occupations (field crop farmers and miners) where other potentially relevant exposures like pesticides and radon may also occur, more research is needed to confirm our findings of an association with crystalline silica, and if so, mechanistic studies to understand the pathways.

Bulky DNA adducts and breast cancer risk in the prospective EPIC-Italy study.

The role of environmental carcinogen exposure in breast cancer development has long been suspected, but no specific association has been identified so far. A few molecular epidemiology studies reported that DNA adducts detected by different methods are associated with a modest increase of breast cancer risk. We aimed to evaluate the association between bulky DNA adducts, detected by the (32)P-postlabelling method in peripheral leukocytes, and the risk of developing breast cancer in the female Italian cohorts of the EPIC (European Prospective Investigation into Cancer and nutrition) study. By using a nested case-control design, breast cancer cases identified in the follow-up of over 30,000 women of EPIC-Italy study have been matched to controls by specific criteria. We measured the levels of bulky DNA adducts by the (32)P-postlabelling method in peripheral leukocytes donated at enrolment. Conditional regression analyses adjusted for selected potential confounders were used. Results on DNA adduct levels were available for 292 cases and 292 matched controls. The mean DNA adduct levels were similar in both groups (P=0.62). Multivariate regression analyses failed to show any significant association between bulky DNA adducts and breast cancer. Our results do not support any association of breast cancer risk with exposure to environmental carcinogens as measured through the levels of bulky DNA adducts in pre-diagnostic white blood cells. Larger studies by using different methods and/or biomarkers are needed to better evaluate the role of specific environmental carcinogens in breast carcinogenesis.