Publications by authors named "Lucia Miligi"

88 Publications

Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes.

J Transl Genet Genom 2021 17;5:200-217. Epub 2021 Jun 17.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk.

Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis.

Results: We discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41, = 1.6 × 10) and FL (β = 11.4, SE = 5.82, = 0.02) but not DLBCL ( = 1.0) or MZL ( = 0.91). For F3, we observed an association with CLL (β = 27.5, SE = 6.51, = 2.4 × 10). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity.

Conclusion: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.
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http://dx.doi.org/10.20517/jtgg.2021.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494431PMC
June 2021

[The new national guidelines for the keeping of the Italian Sinonasal Cancer Registry (ReNaTuNS)].

Epidemiol Prev 2021 Jul-Aug;45(4):296-301

Dipartimento di medicina, epidemiologia e igiene del lavoro e ambientale, Istituto nazionale assicurazione infortuni sul lavoro (Inail), Roma.

Sinonasal cancers (SNC) are rare tumours with predominant occupational aetiology associated with exposures to specific carcinogens. In Italy, SNC incidence has been under compulsory surveillance since 2008, through the National Sinonasal Cancer Registry (ReNaTuNS), a nationwide cancer registry coordinated by the National Institute for Insurance Against Accidents at Work (Inail). The ReNaTuNS has a regional structure with local registries, established at Regional Operating Centres (CORs). Currently, seven Italian Regions are active in SNC search and, together with Inail, have recently released a new version of the national guidelines for keeping the Registry (available on the Inail website). The aim of this text is to present the new guidelines, an updating version, and to underline the relevance of this tool in enforcing the role of the ReNaTuNS, considering the high occupational fraction of SNC and the unicity of the Italian Registry, which collects all the information available on occupational exposures of each SNC case registered. It is recommended that the active search for SNC cases and the analysis of exposure become a systematic and well-organized activity to prevent or reduce risks of exposure and to support and improve the efficiency of the compensation and welfare system.
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http://dx.doi.org/10.19191/EP21.4.P296.086DOI Listing
September 2021

[Mortality and cancer risk in agricultural nursery workers: a cohort study in Tuscany Region (Central Italy)].

Epidemiol Prev 2021 Jul-Aug;45(4):254-262

SS epidemiologia dell'ambiente e del lavoro, SC epidemiologia dei fattori di rischio e degli stili di vita, Istituto per lo studio, la prevenzione e la rete oncologica (ISPRO), Firenze;

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.
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http://dx.doi.org/10.19191/EP21.4.P254.081DOI Listing
September 2021

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

Int J Cancer 2021 Nov 29;149(10):1768-1786. Epub 2021 Jul 29.

Division of Population Health, Centre for Occupational and Environmental Health, University of Manchester, Manchester, UK.

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.
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http://dx.doi.org/10.1002/ijc.33740DOI Listing
November 2021

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

Environ Health 2021 04 28;20(1):49. Epub 2021 Apr 28.

Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

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. 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.
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http://dx.doi.org/10.1186/s12940-021-00729-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082925PMC
April 2021

[The new ReNaTuNS operating manual for nasal sinus tumor case management].

G Ital Med Lav Ergon 2020 12;42(4):242-243

INAIL - Dipartimento di medicina, epidemiologia, igiene del lavoro e ambientale, Roma.

Summary: No abstract available.
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December 2020

Italian pool of asbestos workers cohorts: asbestos related mortality by industrial sector and cumulative exposure.

Ann Ist Super Sanita 2020 Jul-Sep;56(3):292-302

Dipartimento di Biologia e Biotecnologie "Charles Darwin", La Sapienza Università di Roma, Rome, Italy.

Objective: Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers.

Methods: Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period.

Results: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most also from peritoneal and lung cancer and asbestosis, with exposure related trend. Increased mortality was also observed for ovarian cancer and for bladder cancer.

Discussion: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. A large increase in mortality from asbestosis was observed.
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http://dx.doi.org/10.4415/ANN_20_03_07DOI Listing
September 2021

Factors Affecting Asbestosis Mortality Among Asbestos-Cement Workers in Italy.

Ann Work Expo Health 2020 07;64(6):622-635

Unit of Medical Statistics and Cancer Epidemiology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.

Objectives: This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres.

Methods: Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied.

Results: Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR: males 508, 95% confidence interval (CI): 446-563; females 1027, 95% CI: 771-1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75-80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos.

Conclusions: Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos.
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http://dx.doi.org/10.1093/annweh/wxaa037DOI Listing
July 2020

Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Front Oncol 2019 28;9:1539. Epub 2020 Jan 28.

Interdisciplinary Department of Medicine, University of Bari, Bari, Italy.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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http://dx.doi.org/10.3389/fonc.2019.01539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999122PMC
January 2020

Estimation of Occupational Exposure to Asbestos in Italy by the Linkage of Mesothelioma Registry (ReNaM) and National Insurance Archives. Methodology and Results.

Int J Environ Res Public Health 2020 02 6;17(3). Epub 2020 Feb 6.

Unit of Medical Statistics and Cancer Epidemiology, Department of Translational Medicine, University of Eastern Piedmont, Novara, CPO-Piedmont, 28100 Novara, Italy.

The identification and monitoring of occupational cancer is an important aspect of occupational health protection. The Italian law on the protection of workers (D. Leg. 81/2008) includes different cancer monitoring systems for high and low etiologic fraction tumors. Record linkage between cancer registries and administrative data is a convenient procedure for occupational cancer monitoring. We aim to: (i) Create a list of industries with asbestos exposure and (ii) identify cancer cases who worked in these industries. The Italian National Mesothelioma Registry (ReNaM) includes information on occupational asbestos exposure of malignant mesothelioma (MM) cases. We developed using data from seven Italian regions a methodology for listing the industries with potential exposure to asbestos linking ReNaM to Italian National Social Security Institute (INPS) data. The methodology is iterative and adjusts for imprecision and inaccuracy in reporting firm names at interview. The list of asbestos exposing firms was applied to the list of cancer cases (all types associated or possibly associated with asbestos according to International Agency for Research on Cancer (IARC) monograph 100C) in two Italian regions for the indication of possible asbestos exposure. Eighteen percent of the cancer cases showed at least one work period in firms potentially exposing to asbestos, 48% of which in regions different from where the cases lived at diagnosis. The methodology offers support for the preliminary screening of asbestos exposing firms in the occupational history of cancer cases.
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http://dx.doi.org/10.3390/ijerph17031020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037801PMC
February 2020

[Radiofrequency electromagnetic fields, mobile phones, and health effects: where are we now?]

Authors:
Lucia Miligi

Epidemiol Prev 2019 Sep-Dec;43(5-6):374-379

SS Epidemiologia dell'ambiente e del lavoro, SC Epidemiologia dei fattori di rischio e degli stili di vita, Istituto per lo studio, la prevenzione e la rete oncologica (ISPRO), Firenze;

This paper aims to present useful elements for framing the issue of exposure to radio frequencies (RFs), in particular those related to telecommunications, and the possible effects on health also in the light of the rapid evolution of technologies (the advent of 5G). New developments in the field oblige us to reflect on the possible implications in terms of public health. Here, we have preferred to take stock and not to demand a systematic review. The development of telecommunications is creating great interest in all sectors for the possibility of new applications, but is also increasing concern for the effects on health not yet fully known, to the point that there is a growing mobilization against the introduction of 5G both at national and at international level. Epidemiological studies and metanalyses on the relationship between cancer and RFs, particularly those on mobile phones, still identify areas of uncertainty that need to be investigated, and studies on non-cancer effects are growing in number, suggesting the possibility of new risks. The relative scenarios that will open with the 5G trial are likely to change the overall exposure level of the population as a result of major changes in the network architecture. Therefore, it is important to adopt a strongly precautionary approach. Given the strong concerns of the population, the competent institutions should implement information and awareness programmes through adequate risk communication.
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http://dx.doi.org/10.19191/EP19.5-6.P374.107DOI Listing
April 2020

Methylation alteration of as a predictive, diagnostic and prognostic biomarker for chronic lymphocytic leukemia.

Oncotarget 2019 Aug 13;10(48):4987-5002. Epub 2019 Aug 13.

Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, Cagliari, Italy.

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the clonal expansion of malignant B cells. To predict the clinical course of the disease, the identification of diagnostic biomarkers is urgently needed. Aberrant methylation patterns may predict CLL development and its course, being very early changes during carcinogenesis. Our aim was to identify CLL specific methylation patterns and to evaluate whether methylation aberrations in selected genes are associated with changes in gene expression. Here, by performing a genome-wide methylation analysis, we identified several CLL-specific methylation alterations. We focused on the most altered one, at a CpG island located in the body of gene, in our CLL cases compared to healthy controls. This methylation alteration was successfully validated in a larger cohort including 139 CLL and 20 control samples. We also found a positive correlation between methylation level and absolute lymphocyte count, in particular CD19+ B cells, in CLL patients. Moreover, we were able to detect gains of methylation at in blood samples collected years prior to diagnosis. Overall, our results suggest methylation alteration at this CpG island as a biomarker for risk and diagnosis of CLL, and also in the personalized quantification of tumor aggressiveness.
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http://dx.doi.org/10.18632/oncotarget.27080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697638PMC
August 2019

Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.

Occup Environ Med 2019 09;76(9):611-616

Epidemiology Unit - Department of Translational Medicine, CPO Piemonte and University of Eastern Piedmont, Turin, Italy.

Objectives: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis.

Methods: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time.

Results: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer.

Conclusions: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.
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http://dx.doi.org/10.1136/oemed-2019-105779DOI Listing
September 2019

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Genet Epidemiol 2019 10 13;43(7):844-863. Epub 2019 Aug 13.

Medicina Traslazionale, Università del Piemonte Orientale, Vercelli, Italy.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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http://dx.doi.org/10.1002/gepi.22242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763347PMC
October 2019

Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.

Environ Health 2019 08 7;18(1):71. Epub 2019 Aug 7.

Unit of Medical Statistics and Cancer Epidemiology, Department of Translational Medicine, University of Eastern Piedmont, via Solaroli 17, 28100, Novara, Italy.

Background: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos.

Methods: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution.

Results: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%.

Conclusions: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.
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http://dx.doi.org/10.1186/s12940-019-0510-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686495PMC
August 2019

[Reporting a cluster of lymphohaematopoietic cancers and management of the communication process with the community: the experience of a Local health Authority in Tuscany, Italy].

Ig Sanita Pubbl 2019 Mar-Apr;75(2):98-104

SS Epidemiologia dell'Ambiente e del Lavoro, Istituto per lo Studio, la Prevenzione e la Rete Oncologica, Firenze, Italia.

In 2008, some general practitioners (GPs) in the area of Empoli (Tuscany Region, Central Italy), reported to the Local Health Authority (LHA), an unusually high frequency of leukemia deaths among their patients residing in a one of the municipalities of the area. The LHA decided to carry out an epidemiological investigation. An interdepartmental working group was set up, led by the Department of Prevention of the LHA, and made up of representatives of the Institute for Study, Prevention and Cancer Network (ISPRO, Florence), the G. Monasterio Foundation/ Institute of Clinical Physiology of the National Council for Research (CNR) of Pisa, the University of Pisa, the Regional Environmental Protection Agency and community members. Several epidemiological analyses were carried out (namely incidence and mortality analysis, assessment of the residential history of all cases and micro-geographical incidence evaluation, assessment and quantification of local environmental pressures, evaluation of congenital abnormalities). The investigation took over two years to be completed. The work agenda was shared with community members, who contributed to decision-making, study design and the communication plan. Thanks to the interaction with community members, researchers had the chance to become aware of their information needs and of local knowledge concerning the research issues. The final report was published online and presented to citizens in several public meetings. Direct involvement of the local community during project development was found to be useful to reduce the perceived distance between public authorities and the local population, as highlighted in the guidelines on cancer cluster investigations.
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October 2019

Parental occupational exposure to low-frequency magnetic fields and risk of leukaemia in the offspring: findings from the Childhood Leukaemia International Consortium (CLIC).

Occup Environ Med 2019 10 29;76(10):746-753. Epub 2019 Jul 29.

Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.

Objectives: Previously published studies on parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring were inconsistent. We therefore evaluated this question within the Childhood Leukemia International Consortium.

Methods: We pooled 11 case-control studies including 9723 childhood leukaemia cases and 17 099 controls. Parental occupational ELF-MF exposure was estimated by linking jobs to an ELF-MF job-exposure matrix (JEM). Logistic regression models were used to estimate ORs and 95% CIs in pooled analyses and meta-analyses.

Results: ORs from pooled analyses for paternal ELF-MF exposure >0.2 microtesla (µT) at conception were 1.04 (95% CI 0.95 to 1.13) for ALL and 1.06 (95% CI 0.87 to 1.29) for AML, compared with ≤0.2 µT. Corresponding ORs for maternal ELF-MF exposure during pregnancy were 1.00 (95% CI 0.89 to 1.12) for ALL and 0.85 (95% CI 0.61 to 1.16) for AML. No trends of increasing ORs with increasing exposure level were evident. Furthermore, no associations were observed in the meta-analyses.

Conclusions: In this large international dataset applying a comprehensive quantitative JEM, we did not find any associations between parental occupational ELF-MF exposure and childhood leukaemia.
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http://dx.doi.org/10.1136/oemed-2019-105706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817988PMC
October 2019

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

Int J Cancer 2020 02 17;146(4):977-986. Epub 2019 May 17.

Clinical Epidemiology, Ospedale Policlinico San Martino, IRCCS, Genoa, Italy.

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.
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http://dx.doi.org/10.1002/ijc.32393DOI Listing
February 2020

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

Environ Res 2019 06 27;173:300-305. Epub 2019 Mar 27.

Cancer Factor Risk Branch, Regional Cancer Prevention Laboratory, ISPRO-Study, Prevention and Oncology Network Institute, 50139, Florence, Italy. Electronic address:

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-F isoprostane (15-F-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-F-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/m 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-F-IsoP (43%) was observed in the smokers as compared to the non-smokers. The urinary excretion of 15-F-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-F-IsoP was linearly correlated to the length of exposure, regression coefficient (β) = 0.244 ± 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 F-IsoP measure can be a tool for the evaluation of the effectiveness of targeted interventions aimed to reduce exposures to environmental carcinogens.
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http://dx.doi.org/10.1016/j.envres.2019.03.058DOI Listing
June 2019

Late mortality and causes of death among 5-year survivors of childhood cancer diagnosed in the period 1960-1999 and registered in the Italian Off-Therapy Registry.

Eur J Cancer 2019 03 14;110:86-97. Epub 2019 Feb 14.

Department of Hematology and Oncology, University Hospital AOU Meyer, Florence, Italy.

Introduction: Advances in paediatric oncology led to the increase in long-term survival, revealing the burden of therapy-related long-term side effects. We evaluated overall and cause-specific mortality in a large cohort of Italian childhood cancer survivors (CCSs) and adolescent cancer survivors identified through the off-therapy registry.

Materials And Methods: CCSs alive 5 years after cancer diagnosis occurring between 1960 and 1999 were eligible; the last follow-up was between 2011 and 2014. Outcomes were reported as standardised mortality ratios (SMRs) and absolute excess risks (AERs).

Results: Among 12,214 CCSs, 1113 (9.1%) deaths occurred. Survival at 35 years since diagnosis was 87% (95% confidence interval [CI]: 86-88) and at 45 years was 81% (95% CI: 77-84). CCSs had an 11-fold increased risk of death (SMR 95% CI: 10.7-12), corresponding to an AER of 48 (95% CI: 45-51). Mortality decreased by 60% for survivors treated most recently (1990-1999). The most frequent causes of death were recurrence of the original cancer (56%), a subsequent neoplasm (19%) and cardiovascular diseases (5.8%). Among those who survived at least 15 years after diagnosis, a secondary malignancy was the leading cause of death.

Conclusions: This study confirms the impact of recent advances in anticancer therapy in reducing mortality, mainly attributable to recurrence but also to other causes. However, overall mortality continues to be higher than in the general population. A long-term follow-up is needed to prevent late mortality due to secondary neoplasms and non-neoplastic causes in CCSs.
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http://dx.doi.org/10.1016/j.ejca.2018.12.021DOI Listing
March 2019

Pooled study of occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma.

Occup Environ Med 2018 11 18;75(11):798-806. Epub 2018 Aug 18.

Department of Public Health and Clinical Molecular Medicine, University of Cagliari, Cagliari, Italy.

Objectives: To investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study.

Methods: We pooled data on 2854 cases and 10 743 controls from nine studies participating in the InterLymph consortium. Occupational exposures to benzene, toluene and xylene were assigned by a job-exposure matrix, coupled with 'correction' of exposure probability by self-reported or expert-assessed exposure from the individual studies. Cumulative intensity was calculated as the job-specific exposure intensity multiplied by job duration, summed across jobs. Associations were estimated using logistic regression, with inclusion of covariates for study matching factors and other potential confounders. We repeated our main analysis using random-effects meta-analysis to evaluate heterogeneity of effect.

Results: Benzene, toluene and xylene were each associated with MM. For the three solvents, the highest quartile of high-probability cumulative intensity exposure (vs unexposed) was associated with 42% to 63% increased risks of MM. Associations with toluene and xylene exposures were fairly consistent and robust to sensitivity analyses. The estimated effect for benzene was moderately heterogeneous between the studies. Each solvent's association with MM was stronger for exposure occurring within 20 years of diagnosis than with exposure lagged by more than 20 years.

Conclusions: Our study adds important evidence for a role of aromatic hydrocarbon solvents in causation of MM. The difficulty in disentangling individual compounds in this group and a lack of data on potential carcinogenicity of toluene and xylene, in widespread current use, underscore a need for further epidemiological evaluation.
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http://dx.doi.org/10.1136/oemed-2018-105154DOI Listing
November 2018

Anti-hypertensive drugs and skin cancer risk: a review of the literature and meta-analysis.

Crit Rev Oncol Hematol 2018 Feb 13;122:1-9. Epub 2017 Dec 13.

Cancer Risk Factors and Lifestyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. Electronic address:

Introduction: Several anti-hypertensive drugs have photosensitizing properties, however it remains unclear whether long-term users of these drugs are also at increased risk of skin malignancies. We conducted a literature review and meta-analysis on the association between use of anti-hypertensive drugs and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC).

Methods: We searched PubMed, EMBASE, Google Scholar and the Cochrane Library, and included observational and experimental epidemiological studies published until February 28th, 2017. We calculated summary relative risk (SRR) and 95% confidence intervals (95% CI) through random effect models to estimate the risk of skin malignancies among users of the following classes of anti-hypertensive drugs: thiazide diuretics, angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB) and β-blockers. We conducted sub-group and sensitivity analysis to explore causes of between-studies heterogeneity, and assessed publication bias using a funnel-plot based approach.

Results: Nineteen independent studies were included in the meta-analysis. CCB users were at increased skin cancer risk (SRR 1.14, 95% CI 1.07-1.21), and β-blockers users were at increased risk of developing cutaneous melanoma (SRR 1.21, 95% CI 1.05-1.40), with acceptable between-studies heterogeneity (I < 50%). There was no association between thiazide diuretics, ACEi or ARB use and skin cancer risk. We found no evidence of publication bias affecting the results.

Conclusion: Family doctors and clinicians should inform their patients about the increased risk of skin cancer associated with the use of CCB and β-blockers and instruct them to perform periodic skin self-examination. Further studies are warranted to elucidate the observed associations.
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http://dx.doi.org/10.1016/j.critrevonc.2017.12.003DOI Listing
February 2018

Sinonasal cancer in the Italian national surveillance system: Epidemiology, occupation, and public health implications.

Am J Ind Med 2018 03 7;61(3):239-250. Epub 2017 Nov 7.

Department of Occupational and Environmental Medicine, Epidemiology, Hygiene, National Institute for Insurance Against Accidents at Work (INAIL), Rome, Italy.

Background: Sinonasal cancer (SNC) is a rare tumor with predominant occupational etiology associated with exposures to specific carcinogens. The aim of this study is to describe SNC cases recorded in Italy in the period 2000-2016.

Methods: Clinical information, occupational history, and lifestyle habits of SNC cases collected in the Italian Sinonasal Cancer Register were examined. Age-standardized rates were estimated.

Results: Overall, 1529 cases were recorded. The age-standardized incidence rates per 100 000 person-years were 0.65 in men and 0.26 in women. Occupational exposures were predominant among the attributed exposure settings, primarily to wood and leather dusts. Other putative causal agents included chrome, solvents, tannins, formaldehyde, textile dusts, and pesticides. Many cases had unknown exposure.

Conclusions: Epidemiological surveillance of SNC cases and their occupational history is fundamental for monitoring the occurrence of the disease in exposed workers in industrial sectors generally not considered at risk of SNC as well as in non-occupational settings.
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http://dx.doi.org/10.1002/ajim.22789DOI Listing
March 2018

Activation of the aryl hydrocarbon receptor and risk of lymphoma subtypes.

Int J Mol Epidemiol Genet 2017 1;8(4):40-44. Epub 2017 Sep 1.

Department of Medical Sciences and Public Health, Occupational Health Unit, University of Cagliari09042 Monserrato, Italy.

The aryl hydrocarbon receptor (AhR) is a transcription factor implicated in several pathways known to be relevant in lymphomagenesis. Aim of our study was to explore the link between AhR activation and risk of lymphoma subtypes. We used a Dual-Luciferase Assay and a luminometer to detect the activation of the luciferase gene, in HepG2 cells transfected with a specific reporter systems, by a 50 ml serum aliquot of cases of diffuse large B cell lymphoma (N = 108), follicular lymphoma (N = 85), chronic lymphocytic leukemia (N = 72), multiple myeloma (N = 80), and Hodgkin lymphoma (N = 94) and 357 controls who participated in the multicentre Italian study on gene-environment interactions in lymphoma etiology (ItGxE). Risk of each lymphoma subtype associated with AhR activation was calculated with polytomous logistic regression adjusting by age, gender, and study centre. The overall prevalence of AhR activation ranged 13.9-23.6% by subtype, and it varied by study area (8-39%). Risk associated with AhR activation was moderately elevated for follicular lymphoma (OR = 1.56, 95% CI 0.86, 2.80) and chronic lymphocytic leukemia (OR = 1.56, 95% CI 0.83, 2.96). Despite our inconclusive findings about the association with risk of lymphoma subtypes, we showed that the Dual-Luciferase Assay can be reliably and easily applied in population-based studies to detect AhR activation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636915PMC
September 2017

Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure.

Occup Environ Med 2017 12 3;74(12):887-898. Epub 2017 Aug 3.

Department of Translational Medicine, Unit of Medical Statistics and Epidemiology, University of Eastern Piedmont, and CPO-Piemonte, Novara, Italy.

Objective: Asbestos is a known human carcinogen, with evidence for malignant mesothelioma (MM), cancers of lung, ovary, larynx and possibly other organs. MM rates are predicted to increase with a power of time since first exposure (TSFE), but the possible long-term attenuation of the trend is debated. The asbestos ban enforced in Italy in 1992 gives an opportunity to measure long-term cancer risk in formerly exposed workers.

Methods: Pool of 43 previously studied Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding), with mortality follow-up updated to 2010. SMRs were computed for the 1970â€"2010 period, for the major causes, with consideration of duration and TSFE, using reference rates by age, sex, region and calendar period.

Results: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Mortality was significantly increased for all deaths (SMR: men: 1.05, 95% CI 1.03 to 1.06; women: 1.17, 95% CI to 1.12 to 1.22), all malignancies combined (SMR: men: 1.17, 95% CI to 1.14 to 1.20; women: 1.33, 95% CI 1.24 to 1.43), pleural and peritoneal malignancies (SMR: men: 13.28 and 4.77, 95% CI 12.24 to 14.37 and 4.00 to 5.64; women: 28.44 and 6.75, 95% CI 23.83 to 33.69 and 4.70 to 9.39), lung (SMR: men: 1.26, 95% CI 1.21 to 1.31; women: 1.43, 95% CI 1.13 to 1.78) and ovarian cancer (SMR=1.38, 95% CI 1.00 to 1.87) and asbestosis (SMR: men: 300.7, 95% CI 270.7 to 333.2; women: 389.6, 95% CI 290.1 to 512.3). Pleural cancer rate increased during the first 40 years of TSFE and reached a plateau after.

Discussion: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. Pleural cancer mortality reached a plateau at long TSFE, coherently with recent reports.
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http://dx.doi.org/10.1136/oemed-2016-104100DOI Listing
December 2017

Road Traffic Pollution and Childhood Leukemia: A Nationwide Case-control Study in Italy.

Arch Med Res 2016 11;47(8):694-705

Department of Epidemiology, Lazio Regional Health Service, Roma, Italy.

Background: The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes.

Aim Of The Study: We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic.

Methods: We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic-ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children.

Results: We observed an increase in risk for AnLL, and at a lower extent for ALL, with indicators of exposure to traffic pollutants. In particular, the risk was associated to the report of closeness of the house to traffic lights and to the passage of trucks (OR: 1.76; 95% CI 1.03-3.01 for ALL and 6.35; 95% CI 2.59-15.6 for AnLL). The association was shown also in the analyses limited to AML and in the stratified analyses and in respect to the house in different period of life.

Conclusions: Results from the SETIL study provide some support to the association of traffic related exposure and risk for AnLL, but at a lesser extent for ALL. Our conclusion highlights the need for leukemia type specific analyses in future studies. Results support the need of controlling exposure from traffic pollution, even if knowledge is not complete.
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http://dx.doi.org/10.1016/j.arcmed.2017.02.001DOI Listing
November 2016

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.

Nat Commun 2017 02 6;8:14175. Epub 2017 Feb 6.

Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK.

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10), 1q42.13 (rs41271473, P=1.06 × 10), 4q24 (rs71597109, P=1.37 × 10), 4q35.1 (rs57214277, P=3.69 × 10), 6p21.31 (rs3800461, P=1.97 × 10), 11q23.2 (rs61904987, P=2.64 × 10), 18q21.1 (rs1036935, P=3.27 × 10), 19p13.3 (rs7254272, P=4.67 × 10) and 22q13.33 (rs140522, P=2.70 × 10). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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http://dx.doi.org/10.1038/ncomms14175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303820PMC
February 2017

[Communication in the evaluation process of cancer clusters].

Epidemiol Prev 2016 Sep-Oct;40(5Suppl2):65-67

Istituto per lo studio e la prevenzione oncologica (ISPO), Firenze.

Communication is an essential but complex aspect of the management of a suspected cancer cluster. In this paper, it is summarized how this issue has been addressed in the guidelines on the management of cluster developed by the Centers for Disease Control and Prevention (CDCs) in the US and by the Institut de Veille Sanitaire in France. The US guidelines recommend a communication strategy that includes a basic plan, which must be adapted to all steps of the process, a transparent communication, the involvement of the local community, the definition of the subjects involved, and the development of the necessary tools. The French guidelines emphasize that the management of these alarms is both a health and a policy issue, highlighting that this fact has important implications in the communication strategy. Guidelines are useful tools; however, they can lead to an excessive use of proceduralization if the ability to detect features of each cluster is not improved. It is therefore essential to create the opportunity to discuss and share experiences among stakeholders who are actually entitled to respond to these alarms. Some experiences of cancer cluster in Tuscany are used as examples.
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December 2017

[Investigative model for the evaluation of spatio-temporal clusters of childhood cancers].

Epidemiol Prev 2016 Sep-Oct;40(5Suppl2):42-54

Epidemiologo, Milano.

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.
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December 2017

[Documented and suspected risk factors for childhood cancer aetiology].

Epidemiol Prev 2016 Sep-Oct;40(5Suppl2):10-16

Istituto di elettronica e di ingegneria dell'informazione e delle telecomunicazioni, Consiglio nazionale delle ricerche, Genova.

We present an updated summary on risk factors for childhood malignancies, following to previous reviews published on Epidemiologia&Prevenzione and largely based on the monographs of the International Agency for Research on Cancer (IARC). Ionizing radiations are certain carcinogens, with evidence in humans, from studies both on children and on adults. Evidence specifically regarding childhood cancers is available also for other carcinogens, such as tobacco smoking, some solvents, some occupational activities of parents, and some viruses (HIV and EBV). For most carcinogens, information specifically regarding childhood cancer risks is limited, but it is enough to suggest the reduction of exposure, according to a precautionary approach. Available evidence can be helpful in evaluating reports of possible clusters of disease and the association with putative causes.
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December 2017
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