Publications by authors named "Pierluigi Cocco"

131 Publications

Occupational Insecticide Exposure and Risk of Non-Hodgkin Lymphoma: A Pooled Case-Control Study from the InterLymph Consortium.

Int J Cancer 2021 Jul 16. Epub 2021 Jul 16.

Centre for Occupational and Environmental Health, Division of Population 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 (e.g., organophosphates, pyrethroids) and active ingredients (e.g., 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 organochlorine 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. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.33740DOI Listing
July 2021

Prevalence of sleep disruption and determinants of sleepiness in a cohort of Italian hospital physicians: The PRESOMO study.

J Sleep Res 2021 Jun 27:e13377. Epub 2021 Jun 27.

Interdepartmental Sleep Research Centre, Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy.

Nightshift work can cause daytime somnolence and decreased alertness, and can increase risk of medical errors, occupational injuries and car accidents. We used a structured questionnaire, including the Epworth Sleepiness Scale (ESS), to assess the prevalence and the determinants of sleep disruption in 268 Italian University hospital physicians from Cagliari (N = 57), Milan (N = 180) and Pisa (N = 31), who participated in the multicentre study on the prevalence of sleep disturbance among hospital physicians (PRESOMO); 198 of them (74%) were engaged in nightshift work. We explored the association between history of nightshift work and poor sleep quality and daytime somnolence with multivariate logistic regression, adjusting by personal and lifestyle covariates. Age, female gender, taking medication interfering with sleep and an elevated ESS score were significant predictors of poor sleep quality and daytime somnolence. Nightshift work was associated with a higher prevalence of unrestful sleep (84% versus 70%; odds ratio [OR] = 2.4, 95% confidence interval [CI] 1.18-5.05) and daytime dozing (57% versus 35%; OR = 1.9, 95% CI 1.03-3.64), with an upward trend by years of engagement in nightshift work for both conditions (p = .043 and 0.017, respectively), and by number of nightshifts/year for unrestful sleep (p = .024). Such an association was not detected with the ESS scale. Our results suggest that nightshift work significantly affects sleep quality and daytime somnolence in hospital physicians, who might underestimate their daytime dozing problem, when asked to subjectively scale it.
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http://dx.doi.org/10.1111/jsr.13377DOI Listing
June 2021

COVID-19: Heterogeneous Excess Mortality and "Burden of Disease" in Germany and Italy and Their States and Regions, January-June 2020.

Front Public Health 2021 7;9:663259. Epub 2021 May 7.

Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, University of Cologne, Cologne, Germany.

Total mortality and "burden of disease" in Germany and Italy and their states and regions were explored during the first COVID-19 wave by using publicly available data for 16 German states and 20 Italian regions from January 2016 to June 2020. Based on expectations from 2016 to 2019, simplified Standardized Mortality Ratios (SMRs) for deaths occurring in the first half of 2020 and the effect of changed excess mortality in terms of "burden of disease" were assessed. Moreover, whether two German states and 19 Italian cities appropriately represent the countries within the European monitoring of excess mortality for public health action (EuroMOMO) network was explored. Significantly elevated SMRs were observed (Germany: week 14-18, Italy: week 11-18) with SMR peaks in week 15 in Germany (1.15, 95%-CI: 1.09-1.21) and in week 13 in Italy (1.79, 95%-CI: 1.75-1.83). Overall, SMRs were 1.00 (95%-CI: 0.97-1.04) in Germany and 1.06 (95%-CI: 1.03-1.10) in Italy. Significant SMR heterogeneity was found within both countries. Age and sex were strong modifiers. Loss of life expectancy was 0.34 days (1.66 days in men) for Germany and 5.3 days (6.3 days in men) for Italy [with upper limits of 3 and 6 weeks among elderly populations (≥65 years) after maximum potential bias adjustments]. Restricted data used within EuroMOMO neither represents mortality in the countries as a whole nor in their states and regions adequately. Mortality analyses with high spatial and temporal resolution are needed to monitor the COVID-19 pandemic's course.
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http://dx.doi.org/10.3389/fpubh.2021.663259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137836PMC
May 2021

Biomarkers of Low-Level Environmental Exposure to Benzene and Oxidative DNA Damage in Primary School Children in Sardinia, Italy.

Int J Environ Res Public Health 2021 04 27;18(9). Epub 2021 Apr 27.

Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, 092109 Cagliari, Italy.

Background: The main anthropic sources of exposure to airborne benzene include vehicular traffic, cigarette smoke, and industrial emissions.

Methods: To detect early genotoxic effects of environmental exposure to benzene, we monitored environmental, personal, and indoor airborne benzene in children living in an urban area and an area near a petrochemical plant. We also used urinary benzene and S-phenylmercapturic acid (S-PMA) as biomarkers of benzene exposure and urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of early genotoxic effects.

Results: Although always below the European Union limit of 5 μg/m, airborne benzene levels were more elevated in the indoor, outdoor, and personal samples from the industrial surroundings compared to the urban area ( = 0.026, = 0.005, and = 0.001, respectively). Children living in the surroundings of the petrochemical plant had urinary benzene values significantly higher than those from the urban area in both the morning and evening samples ( = 0.01 and = 0.02, respectively). Results of multiple regression modelling showed that age was a significant predictor of 8-OHdG excretion, independent of the sampling hour. Moreover, at the low exposure level experienced by the children participating in this study, neither personal or indoor airborne benzene level, nor personal monitoring data, affected 8-OHdG excretion.

Conclusions: Our results suggest the importance of biological monitoring of low-level environmental exposure and its relation to risk of genotoxic effects among children.
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http://dx.doi.org/10.3390/ijerph18094644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123794PMC
April 2021

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

Environ Health 2021 Apr 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

Response of the Cardiac Autonomic Control to Exposure to Nanoparticles and Noise: A Cross-Sectional Study of Airport Ground Staff.

Int J Environ Res Public Health 2021 03 3;18(5). Epub 2021 Mar 3.

Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy.

Airport activity causes the emission of particulate matter and noise, two environmental contaminants and potential health hazards, particularly for the personnel operating nearby taxiways. We explored the association between exposure to fine/ultrafine particles (UFPs) and noise with heart rate variability (HRV), an early indicator of cardiovascular autonomic response, among a sample of airport ground staff. Between May and June 2018, thirty-four male operators (mean age = 43 years and SD = 6.7) underwent personal monitoring of exposure to nanoparticles and noise, and HRV during their work activity. We conducted univariate and multivariate analysis to test the effect of UFP and noise exposure HRV. Total Lung Deposition Surface Area (LDSA) was significantly associated with a decrease in HRV Total Power and Triangular index ( = -0.038 = 0.016 and = -7.8 × 10, = 0.042, respectively). Noise peak level showed an opposite effect, which was significant for Total Power ( = 153.03, = 0.027), and for Triangular index ( = 0.362, = 0.035). Further investigation is warranted to clarify the effect of the concurrent exposure to UFPs and noise on early changes of cardiac autonomic regulation.
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http://dx.doi.org/10.3390/ijerph18052507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967637PMC
March 2021

Dental caries and quality of life among preschool children: a hospital-based nested case-control study.

Br Dent J 2020 Nov 26. Epub 2020 Nov 26.

Hacettepe University, Faculty of Medicine, Department of Public Health, Ankara, 06100, Turkey.

Introduction Oral health-related quality of life is a reflection of general health and wellbeing; related problems stand as major public health issues.Aim To investigate the potential association between dental caries and quality of life (QoL) among children aged 5-6 years old.Materials and methods Oral examination of 310 children admitted to a paediatric dentistry clinic was performed by using the International Caries Detection and Assessment System II (ICDAS-II) and the QoL was assessed using the Early Childhood Oral Health Impact Scale. A nested case-control study was conducted with all 104 QoL-unaffected children as the controls and a random sample of 104 QoL-affected children as the cases. Relative risk (RR) and its 95% confidence interval (CI) values were calculated to interpret potential associations.Results Gender distribution was similar by case controls (52.9% vs 51.0% were females, respectively). Early childhood caries (ECC) was detected in 78.8% of cases and 19.2% of controls. In binary analysis of the QoL (with a cutpoint of 2), low parental education, having a sibling, dental visit history for complaints and irregular/no toothbrushing were detected as significant predictors of poor QoL (p value <0.001). The RR of negative impact on QoL was fourfold (95% CI 2.64-5.69) among children having ECC, revealing a significant upward trend of impaired QoL with increasing ICDAS-II scores (t = 13.323; p value <0.001).Conclusion All patients should be evaluated thoroughly for social and psychological problems, besides functional and aesthetic in dental visits.
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http://dx.doi.org/10.1038/s41415-020-2317-9DOI Listing
November 2020

Haemolymphatic cancer among children in Sardinia, Italy: 1974-2003 incidence.

BMJ Open 2020 11 3;10(11):e037163. Epub 2020 Nov 3.

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

Objectives: To explore the time trend and geographical distribution of childhood leukaemia incidence over the territory of the Italian region of Sardinia.

Setting: All hospitals departments, diagnostic centres and social security agencies in Sardinia were regularly screened in 1974-2003 to identify, register and review the diagnoses of incident cases of haematological malignancies (HM).

Participants: The whole child population aged 0-14 resident in Sardinia.

Primary And Secondary Outcome Measures: Incidence and time trend of childhood HM and childhood acute lymphoblastic leukaemia (ALL) over the study period, and use of Bayesian methods to plot the probability of areas with excess incidence on the regional map.

Results: Overall, 675 HM cases, including 378 ALL cases, occurred among children aged 0-14 years resident in Sardinia in 1974-2003, with an incidence rate of 6.97×10 (95% CI 6.47 to 7.51) and 3.85×10 (95% CI 3.48 to 4.26), respectively. Incidence of HM and ALL showed an upward trend along the study period especially among females. Three communes out of the 356 existing in 1974, namely Ittiri, Villa San Pietro and Carbonia, stand out as areas with excess incidence of HM and ALL in particular and another, Carloforte, for ALL only.

Conclusions: Our results might serve as convincing arguments for extending the coverage of routine cancer registration over the whole Sardinian population, while prompting further research on the genetic and environmental determinants in the areas at risk.
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http://dx.doi.org/10.1136/bmjopen-2020-037163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640504PMC
November 2020

Occupational exposure to organic dust and risk of lymphoma subtypes in the EPILYMPH case-control study.

Scand J Work Environ Health 2021 Jan 25;47(1):42-51. Epub 2020 Sep 25.

Department of Medical Sciences and Public Health, Occupational Medicine unit, University of Cagliari, Monserrato (Cagliari) Italy.

Objectives This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case-control study, conducted in six European countries in 1998-2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01-4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00-4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95-4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.
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http://dx.doi.org/10.5271/sjweh.3925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801142PMC
January 2021

Schrödinger's Worker: Are They Positive or Negative for SARS-CoV-2?

Int J Environ Res Public Health 2020 08 31;17(17). Epub 2020 Aug 31.

Department of Medical Sciences and Public Health, Occupational Medicine Unit, University of Cagliari, SS 554, km 4.500, 09042 Monserrato (Cagliari), Italy.

In these days of 2020, tests for the diagnosis of SARS-CoV-2, and their use in the context of health surveillance of workers, are becoming popular. Nevertheless, their sensitivity and specificity could vary on the basis of the type of test used and on the moment of infection of the subject tested. The aim of this viewpoint paper is to make employers, workers, occupational physicians, and public health specialists think about the limits of diagnostic tests currently available, and the possible implication related to the erroneous and incautious assignment of "immunity passports" or "risk-free certificates" to workers during screening campaigns in workplaces.
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http://dx.doi.org/10.3390/ijerph17176316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504136PMC
August 2020

Association of ionizing radiation dose from common medical diagnostic procedures and lymphoma risk in the Epilymph case-control study.

PLoS One 2020 10;15(7):e0235658. Epub 2020 Jul 10.

CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Medical diagnostic X-rays are an important source of ionizing radiation (IR) exposure in the general population; however, it is unclear if the resulting low patient doses increase lymphoma risk. We examined the association between lifetime medical diagnostic X-ray dose and lymphoma risk, taking into account potential confounding factors, including medical history. The international Epilymph study (conducted in the Czech-Republic, France, Germany, Ireland, Italy, and Spain) collected self-reported information on common diagnostic X-ray procedures from 2,362 lymphoma cases and 2,465 frequency-matched (age, sex, country) controls. Individual lifetime cumulative bone marrow (BM) dose was estimated using time period-based dose estimates for different procedures and body parts. The association between categories of BM dose and lymphoma risk was examined using unconditional logistic regression models adjusting for matching factors, socioeconomic variables, and the presence of underlying medical conditions (atopic, autoimmune, infectious diseases, osteoarthritis, having had a sick childhood, and family history of lymphoma) as potential confounders of the association. Cumulative BM dose was low (median 2.25 mGy) and was not positively associated with lymphoma risk. Odds ratios (ORs) were consistently less than 1.0 in all dose categories compared to the reference category (less than 1 mGy). Results were similar after adjustment for potential confounding factors, when using different exposure scenarios, and in analyses by lymphoma subtype and by type of control (hospital-, population-based). Overall no increased risk of lymphoma was observed. The reduced ORs may be related to unmeasured confounding or other sources of systematic bias.We found little evidence that chronic medical conditions confound lymphoma risk and medical radiation associations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235658PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351167PMC
September 2020

Occupational exposure to ionizing radiation and risk of lymphoma subtypes: results of the Epilymph European case-control study.

Environ Health 2020 04 25;19(1):43. Epub 2020 Apr 25.

Department of Medical Sciences and Public Health, University of Cagliari, SS554, km 4.500, 09042, Monserrato (Cagliari), Italy.

Background: Evidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels.

Methods: We investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupational history of study subjects, We calculated the Odds Ratio (OR) and its 95% confidence interval (95% CI) for lymphoma (all subtypes combined), B-cell lymphoma, and its major subtypes using unconditional, polytomous logistic regression adjusting for age, gender, and education.

Results: We did not observe an association between exposure metrics of external and internal radiation and risk of lymphoma (all subtypes), nor with B-cell lymphoma, or its major subtypes, at the levels regularly experienced in occupational settings. An elevated risk of diffuse large B cell lymphoma was observed among the most likely exposed study subjects with relatively higher exposure intensity, which would be worth further investigation.

Conclusions: Further investigation is warranted on risk of B cell lymphoma subtypes associated with low-level occupational exposure to external ionizing radiation, and to clarify whether lymphoma should be included among the cancer outcomes related to ionizing radiation.
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http://dx.doi.org/10.1186/s12940-020-00596-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183712PMC
April 2020

Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study.

Cancer Epidemiol Biomarkers Prev 2020 05 27;29(5):1074-1078. Epub 2020 Feb 27.

Emory University, Atlanta, Georgia.

Background: Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis.

Methods: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated ( < 5 × 10) with high-density lipoprotein (HDL, = 164), low-density lipoprotein (LDL, = 137), total cholesterol (TC, = 161), and triglycerides (TG, = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance-weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI).

Results: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00-1.30) and MZL (OR = 1.09; 95% CI, 1.01-1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83-0.99), all at nominal significance ( < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99-1.19; = 0.087). No associations were noteworthy after adjusting for multiple testing.

Conclusions: We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes.

Impact: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196490PMC
May 2020

Reply to Comment on Lecca, L.I.; Portoghese, I.; Mucci, N.; Galletta, M.; Meloni, F.; Pilia, I.; Marcias, G.; Fabbri, D.; Fostinelli, J.; Lucchini, R.G.; Cocco, P.; Campagna, M. Association between Work-Related Stress and QT Prolongation in Male Workers.

Int J Environ Res Public Health 2020 01 14;17(2). Epub 2020 Jan 14.

Department of Medical Sciences and Public Health, University of Cagliari, Blocco I, SS 554, km 4,500, 09042 Monserrato, Italy.

We appreciate the interest raised by our paper on the association between conditions linked to work-related stress and the prolongation of the QT interval on the electrocardiogram [...].
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http://dx.doi.org/10.3390/ijerph17020510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013757PMC
January 2020

Pulmonary Function and CT Scan Imaging at Low-Level Occupational Exposureto Asbestos.

Int J Environ Res Public Health 2019 12 19;17(1). Epub 2019 Dec 19.

Department of Medical Sciences and Public Health, Occupational Health unit, University of Cagliari, Asse didattico-Blocco I SS 554, 09042 Monserrato, Italy.

: In spite of the reduced exposure level, and its ban in numerous countries, compensation claims for asbestos-related diseases are far from decreasing. : We used retrospective exposure assessment techniques to explore respiratory function and a computerized tomography (CT) scan in relation to past asbestos exposure in 115 male workers retired from an acrylic and polyester fiber plant. Based, on detailed information on exposure circumstances, we reconstructed a cumulative exposure estimate for each patient. : Time-weighted average exposure in our study population was 0.24 fibers/ml (95% confidence inteval (CI) 0.19-0.29), and the average cumulative exposure was 4.51 fibers/mL-years (95% CI 3.95-5.07). Exposure was elevated among maintenance workers, compared to other jobs ( = 0.00001). Respiratory function parameters did not vary in relation to the exposure estimates, nor to CT scan results. Risk of interstitial fibrosis showed a significant upward trend (Wald test for trend = 2.62, = 0.009) with cumulative exposure to asbestos; risk associated with 5.26 fibers/mL-years or more, was 8-fold (95% CI 1.18-54.5). : Our results suggest that a CT scan can detect pleuro-parenchymal lung alterations at asbestos exposure levels lower than previously thought, in absence of respiratory impairment. Further studies are required to validate our techniques of retrospective assessment of asbestos exposure.
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http://dx.doi.org/10.3390/ijerph17010050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981734PMC
December 2019

Indexes of cardiac autonomic profile detected with short term Holter ECG in health care shift workers: a cross sectional study.

Med Lav 2019 Dec 17;110(6):437-445. Epub 2019 Dec 17.

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

Background: The assessment of early effect of shift work-related circadian rhythms desynchronization and work-related stress in health care workers has gained a primary role among the duties of the occupational physician.

Objectives: Aim of our study was to assess the cardiac autonomic modulation through quantification of sinus rhythm variability, as an index of the adaptability to shift work of the cardiovascular system in healthcare shift workers.

Methods: We measured Heart Rate Variability (HRV) by short-term (60 minutes) Holter Electrocardiography (ECG) during the regular duties in the respective department of 42 healthcare workers (31 nurses and 11 physicians) of an Italian Hospital (12 male and 30 females, aged 24-58 years), working on 3 shifts with a forward fast rotation with rest at the end of the night shift (7 am - 2 pm; 2 pm - 10 pm; 10 pm - 7 am) or in a fixed daytime shift (8 am - 2 pm). Measurements were all performed between 9 am and 12 am for fixed day workers and between 9 am and 12 pm or between 10 pm and 1 am for shift workers. The following HRV parameters were compared between the subgroups of shift workers and daytime workers: mean heart rate (HR), standard deviation of all normal RR (NN) intervals (SDNN), standard deviation of the averages of NN intervals in all 5-minute segments of a recording (SDaNN) and the triangular index (the integral of the density distribution divided by the maximum of the density distribution). We used parametric tests for independent series to compare HRV parameters by subgroups within the study subjects. We also tested correlation between the variables of interest and the association between HRV and shift work modality, along with other covariates, by means of a multiple linear regression analysis.

Results: We found significantly lower values of SDaNN in shift workers compared with workers engaged solely on day shifts (50.80 ms vs 66.71 ms; p=0,014). The mean heart rate did not show any significant difference between day workers and shift workers (85.78 bmp vs 85.53 bpm respectively). Multivariate analysis showed a significant association between SDNN and female gender and age, while no significant associations were found between HRV and shift work.

Discussion: The autonomic control of the heart rhythm could be disrupted by desynchronization of the biological rhythm secondary to the organization of shift work and night work. Shift work is an important factor of social and biological distress, influencing the adaptability of the cardiovascular system to stimuli and demands of work organization.
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http://dx.doi.org/10.23749/mdl.v110i6.8048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809936PMC
December 2019

Association between Work-Related Stress and QT Prolongation in Male Workers.

Int J Environ Res Public Health 2019 11 28;16(23). Epub 2019 Nov 28.

Department of Medical Sciences and Public Health, University of Cagliari, Blocco I, SS 554, km 4,500, 09042 Monserrato, Italy.

Background: Work-related stress is a potential cardiovascular risk factor, but the underlying mechanism is not fully explained. The autonomic nervous system control of cardiac function might play a specific role; therefore, monitoring the QT interval in the electrocardiogram can highlight an autonomic imbalance induced by occupational stressors. The aim of our study was to explore the QT interval parameters as early indicators of imbalance of the autonomic cardiac function in relation to work-related stress.

Methods: During 2015-2016 annual workplace health surveillance, we measured work-related stress in 484 workers of a logistic support company using the Health and Safety Executive (HSE) tool. We assessed the frequency-corrected QT (QTc) interval and the QT index (QTi) on the electrocardiogram of each participant, and collected demographic and clinical data. We compared the QTc values by the four Karasek's categories (active/passive jobs, low/high strain job), and by job support (present/lacking), and conducted multivariate analysis to adjust for possible confounders.

Results: The results of the multivariate regression analysis showed that QTc was prolonged among workers operating at a specific site where stress level was found to be elevated. Regular physical activity showed a beneficial effect against QTc prolongation. We did not observe an effect on QTc length by the cross-combined Karasek's categories of job control, job demand, and job support.

Conclusions: Our study suggests subclinical effects of conditions associated with work-related stress on the autonomic regulation of cardiac function. Further research is warranted to elucidate the combined effect of work organization and lifestyle factors on autonomic cardiac function.
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http://dx.doi.org/10.3390/ijerph16234781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926840PMC
November 2019

Estimation of Source-Specific Occupational Benzene Exposure in a Population-Based Case-Control Study of Non-Hodgkin Lymphoma.

Ann Work Expo Health 2019 10;63(8):842-855

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology Genetics, National Cancer Institute, Bethesda, MD, USA.

Objectives: Occupational exposures in population-based case-control studies are increasingly being assessed using decision rules that link participants' responses to occupational questionnaires to exposure estimates. We used a hierarchical process that incorporated decision rules and job-by-job expert review to assign occupational benzene exposure estimates in a US population-based case-control study of non-Hodgkin lymphoma.

Methods: We conducted a literature review to identify scenarios in which occupational benzene exposure has occurred, which we grouped into 12 categories of benzene exposure sources. For each source category, we then developed decision rules for assessing probability (ordinal scale based on the likelihood of exposure > 0.02 ppm), frequency (proportion of work time exposed), and intensity of exposure (in ppm). The rules used the participants' occupational history responses and, for a subset of jobs, responses to job- and industry-specific modules. For probability and frequency, we used a hierarchical assignment procedure that prioritized subject-specific module information when available. Next, we derived job-group medians from the module responses to assign estimates to jobs with only occupational history responses. Last, we used job-by-job expert review to assign estimates when job-group medians were not available or when the decision rules identified possible heterogeneous or rare exposure scenarios. For intensity, we developed separate estimates for each benzene source category that were based on published measurement data whenever possible. Frequency and intensity annual source-specific estimates were assigned only for those jobs assigned ≥75% probability of exposure. Annual source-specific concentrations (intensity × frequency) were summed to obtain a total annual benzene concentration for each job.

Results: Of the 8827 jobs reported by participants, 8% required expert review for one or more source categories. Overall, 287 (3.3%) jobs were assigned ≥75% probability of exposure from any benzene source category. The source categories most commonly assigned ≥75% probability of exposure were gasoline and degreasing. The median total annual benzene concentration among jobs assigned ≥75% probability was 0.11 ppm (interquartile range: 0.06-0.55). The highest source-specific median annual concentrations were observed for ink and printing (2.3 and 1.2 ppm, respectively).

Conclusions: The applied framework captures some subject-specific variability in work tasks, provides transparency to the exposure decision process, and facilitates future sensitivity analyses. The developed decision rules can be used as a starting point by other researchers to assess occupational benzene exposure in future population-based studies.
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http://dx.doi.org/10.1093/annweh/wxz063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788340PMC
October 2019

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

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

Clustered protocadherins methylation alterations in cancer.

Clin Epigenetics 2019 07 9;11(1):100. Epub 2019 Jul 9.

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

Background: Clustered protocadherins (PCDHs) map in tandem at human chromosome 5q31 and comprise three multi-genes clusters: α-, β- and γ-PCDH. The expression of this cluster consists of a complex mechanism involving DNA hub formation through DNA-CCTC binding factor (CTCF) interaction. Methylation alterations can affect this interaction, leading to transcriptional dysregulation. In cancer, clustered PCDHs undergo a mechanism of long-range epigenetic silencing by hypermethylation.

Results: In this study, we detected frequent methylation alterations at CpG islands associated to these clustered PCDHs in all the solid tumours analysed (colorectal, gastric and biliary tract cancers, pilocytic astrocytoma), but not hematologic neoplasms such as chronic lymphocytic leukemia. Importantly, several altered CpG islands were associated with CTCF binding sites. Interestingly, our analysis revealed a hypomethylation event in pilocytic astrocytoma, suggesting that in neuronal tissue, where PCDHs are highly expressed, these genes become hypomethylated in this type of cancer. On the other hand, in tissues where PCDHs are lowly expressed, these CpG islands are targeted by DNA methylation. In fact, PCDH-associated CpG islands resulted hypermethylated in gastrointestinal tumours.

Conclusions: Our study highlighted a strong alteration of the clustered PCDHs methylation pattern in the analysed solid cancers and suggested these methylation aberrations in the CpG islands associated with PCDH genes as powerful diagnostic biomarkers.
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http://dx.doi.org/10.1186/s13148-019-0695-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617643PMC
July 2019

The Metabolomic Profile of Lymphoma Subtypes: A Pilot Study.

Molecules 2019 Jun 26;24(13). Epub 2019 Jun 26.

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

Lymphoma defines a group of different diseases. This study examined pre-treatment plasma samples from 66 adult patients (aged 20-74) newly diagnosed with any lymphoma subtype, and 96 frequency matched population controls. We used gas chromatography-mass spectrometry (GC-MS) to compare the metabolic profile by case/control status and across the major lymphoma subtypes. We conducted univariate and multivariate analyses, and partial least square discriminant analysis (PLS-DA). When compared to the controls, statistically validated models were obtained for diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and Hodgkin lymphoma (HL), but not follicular lymphoma (FL). The metabolomic analysis highlighted interesting differences between lymphoma patients and population controls, allowing the discrimination between pathologic and healthy subjects: Important metabolites, such as hypoxanthine and elaidic acid, were more abundant in all lymphoma subtypes. The small sample size of the individual lymphoma subtypes prevented obtaining PLS-DA validated models, although specific peculiar features of each subtype were observed; for instance, fatty acids were most represented in MM and HL patients, while 2-aminoadipic acid, 2-aminoheptanedioic acid, erythritol, and threitol characterized DLBCL and CLL. Metabolomic analysis was able to highlight interesting differences between lymphoma patients and population controls, allowing the discrimination between pathologic and healthy subjects. Further studies are warranted to understand whether the peculiar metabolic patterns observed might serve as early biomarkers of lymphoma.
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http://dx.doi.org/10.3390/molecules24132367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650891PMC
June 2019

Silica, silicosis and lung cancer: what level of exposure is acceptable?

Med Lav 2018 Dec 20;109(6):478-480. Epub 2018 Dec 20.

Department of Public Health, University of Naples Federico II, Italy.

Silica, silicosis and lung cancer: what level of exposure is acceptable?
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http://dx.doi.org/10.23749/mdl.v109i6.7928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682183PMC
December 2018

Work Related Stress, Well-Being and Cardiovascular Risk among Flight Logistic Workers: An Observational Study.

Int J Environ Res Public Health 2018 09 7;15(9). Epub 2018 Sep 7.

Department of Medical Sciences and Public Health, University of Cagliari, Asse Didattico E, SS 554, km 4,500, 09042 Monserrato, Italy.

Work-related stress is a known occupational hazard, with a putative role on the development of cardiovascular diseases (CVD). Although several investigations have explored the association in various workplace scenarios, none have focused on the airport flight logistic support personnel, a transportation business of crucial importance, potentially exposed to job stress and consequently to an increase in CVD risk. We explored the relationship between work-related stress and cardiovascular risk in 568 healthy workers of a flight logistic support company using the Health and Safety Executive questionnaire, the Framingham Heart Study General Cardiovascular Disease (CVD) Risk Prediction Score, and the WHO general well-being index (WHO-5). We used univariate and multivariate statistical methods to take account of possible confounders. Our results show that a low job support significantly increases the CVD risk score and decreases the WHO well-being index with reference to subjects reporting high support on the job. In addition, the well-being index of workers with high strain jobs appears lower in respect to workers employed in low strain job. The multivariate analysis confirms a protective effect of job support, and shows a detrimental influence on CVD risk by physical inactivity, regular intake of alcohol, and a low educational level. In addition, job control, job support, low strain, and high demand coupled with high control (active job) showed a beneficial effect on psychological well-being. Our results suggest that a combination of general risk factors and organizational factors contributes to increase CVD risk and well-being, representing a crucial target for intervention strategies to promote health in the workplace.
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http://dx.doi.org/10.3390/ijerph15091952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164722PMC
September 2018

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

HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes.

Cancer Res 2018 07 7;78(14):4086-4096. Epub 2018 May 7.

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

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci ( trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. HLA gene diversity reduces risk for non-Hodgkin lymphoma. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-2900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065509PMC
July 2018

Assessment of DNA damages in lymphocytes of agricultural workers exposed to pesticides by comet assay in a cross-sectional study.

Biomarkers 2018 Jul 2;23(5):462-473. Epub 2018 Mar 2.

a Interdisciplinary Department of Medicine (DIM), Section "B. Ramazzini" , University Hospital "Policlinico", Unit of Occupational Medicine, School of Medicine, University of Bari , Bari , Italy.

Purpose: To assess the predictive power of the comet assay in the context of occupational exposure to pesticides.

Materials And Methods: The recruited subjects completed a structured questionnaire and gave a blood sample. Exposure to pesticides was measured by means of an algorithm based on Dosemeci's work (Agricultural Health Study). Approximately 50 images were analyzed for each sample via fluorescence microscopy. The extent of DNA damage was estimated by tail moment (TM) and is the product of tail DNA (%) and tail Length.

Results: Crude significant risks (odds ratios, ORs) for values higher than the 75th percentile of TM were observed among the exposed subjects (score > 1). The frequency of some confounding factors (sex, age and smoking) was significantly higher among the exposed workers. A significant dose-effect relationship was observed between TM and exposure score. Significant high-risk estimates (ORs), adjusted by the studied confounding factors, among exposure to pesticides and TM, % tail DNA and tail length were confirmed using unconditional logistic regression models.

Conclusions: The adjusted associations (ORs) between the comet parameters and exposure to pesticides were significant. The sensitivity of the comet test was low (41%), the specificity (89%) and the predictive positive value (0.77) were found acceptable.
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http://dx.doi.org/10.1080/1354750X.2018.1443513DOI Listing
July 2018

Study of congenital malformations among the progeny of the personnel of an interforce military shooting range in Sardinia, Italy.

Med Lav 2018 02 1;109(1):48-56. Epub 2018 Feb 1.

Dipartimento di Scienze Mediche e Sanità Pubblica, Università di Cagliari.

Background: Claims of an excess of congenital malformations in a village nearby the military shooting range of Salto di Quirra (PISQ), Sardinia have attracted media attention.

Objective: To verify such reports with a retrospective study of the reproductive history of the PISQ personnel.

Methods: In 2011, we interviewed 390 soldiers employed at the PISQ shooting range (86.7% of the total workforce) about their reproductive history, including age at first conception, number of live births and spontaneous abortions, and cases of malformations among their progeny, as well as work history and lifestyle habits. We used a job-exposure matrix to assess occupational exposure to radiofrequency, extremely low frequency electromagnetic fields, solvents and nanoparticles, and whether holding an operative job in the shooting range areas.

Results: The rate of congenital malformations among the progeny of the study subjects was close to the expectation (20.2x10^-3 live births, 95% CI 6.3-34.0; 8 cases observed versus 8.6 expected based on the 2005 rate of the Emilia Romagna region), it was lower in the years subsequent to the onset of service at PISQ (11.0x10^-3, 95% CI 0.0-26.1; two cases observed versus 3.9 expected), and it did not vary by residence in the surrounding villages or elsewhere. None of the exposures we assessed was associated with an increase in the rate of congenital malformations.

Conclusions: The limited statistical power of our study allows to exclude that a strong excess of congenital malformations occurred among the progeny of the PISQ shooting range personnel.
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http://dx.doi.org/10.23749/mdl.v109i1.6617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682155PMC
February 2018