Enrico Oddone

Occupational exposures and colorectal cancers: A quantitative overview of epidemiological evidence

A traditional belief widespread across the biomedical community was that dietary habits and genetic predisposition were the basic factors causing colorectal cancer. In more recent times, however, a growing evidence has shown that other determinants can be very important in increasing (or reducing) incidence of this malignancy. The hypothesis that environmental and occupational risk factors are associated with colorectal cancer is gaining ground, and high risks of colorectal cancer have been reported among workers in some industrial branches. The aim of this study was to investigate the epidemiologic relationship between colorectal cancer and occupational exposures to several industrial activities, by means of a scientific literature review and meta-analysis. This work pointed out increased risks of colorectal cancer for labourers occupied in industries with a wide use of chemical compounds, such as leather (RR = 1.70, 95%CI: 1.24-2.34), basic metals (RR = 1.32, 95%CI: 1.07-1.65), plastic and rubber manufacturing (RR = 1.30, 95%CI: 0.98-1.71 and RR = 1.27, 95%CI: 0.92-1.76, respectively), besides workers in the sector of repair and installation of machinery exposed to asbestos (RR = 1.40, 95%CI: 1.07-1.84). Based on our results, the estimated crude excess risk fraction attributable to occupational exposure ranged from about 11% to about 15%. However, homogeneous pattern of association between colorectal cancer and industrial branches did not emerge from this review.

Female Breast Cancer and Electrical Manufacturing: Results of a Nested Case-control Study

Female Breast Cancer and Electrical Manufacturing: Results of a Nested Case‐control Study: Enrico ODDONE, et al. Department of Public Health, Experimental and Forensic Medicine, Occupational Medicine Unit, University of Pavia, Italy—

Female breast cancer in Lombardy, Italy (2002-2009): a case-control study on occupational risks.

BACKGROUND The role of occupational exposures in breast cancer development is still uncertain and, to our knowledge, no studies have been recently carried out in Italy to provide a comprehensive estimation of this possible risk. METHODS Based on administrative data, a case-control study was carried out recruiting all incident cases of female breast cancer in the period 2002-2009, aged between 35 and 69 years, residing in Lombardy, Italy. Controls were randomly sampled from all women residing in Lombardy as of December 31, 2005. Occupational histories, including blue-collar status, were available from 1974 through record linkage with a social security pension database, and were obtained for 11,188 cases and 25,329 controls. Adjusted odds ratios (ORs) and corresponding 90% confidence intervals (CIs) were calculated using multiple unconditional logistic regression models, including terms for sectors of longest employment and for duration of employment. Multiple comparisons were accounted for according to the Benjamini-Hochberg method. RESULTS The ORs for female breast cancer were modestly but significantly increased for employment in electrical manufacturing (OR 1.12, 90%CI 1.04-1.21), textile (OR 1.08, 90%CI 1.02-1.15), paper (OR 1.25, 90%CI 1.06-1.46) and rubber (OR 1.26, 90%CI 1.03-1.54) industries. Analysis by duration of employment within sectors showed significantly increased ORs for electrical manufacturing and rubber industries. After adjustment for multiple comparisons no estimates remained statistically significant. CONCLUSIONS Although with several limitations, our results point to a possible role of exposures in electrical manufacturing, textile, paper and rubber industries in the process leading to breast cancer. An in-dept study for the electrical manufacturing industry has been already planned.

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

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 1970–2010 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.

Monitoring Surface Contamination by Antineoplastic Drugs in Italian Hospitals: Performance-Based Hygienic Guidance Values (HGVs) Project

Antineoplastic drugs (ADs) will continue to represent a potential risk for personnel involved in the handling of these compounds and great concerns have been raised by the presence of ADs in many surveyed workplaces. Eight hospitals were investigated by means of wipe sampling for surface residue determination. Each wipe sample was tested for five ADs considered suitable exposure markers. Cyclophosphamide (CP), gemcitabine (GEM), 5-fluorouracil (5-FU), platinum-containing drugs (Pt), and epi-doxorubicin (EPI) contamination levels were measured in 85 per cent of the studied pharmacies and 93 per cent of outpatient care units (OpCUs). This study showed that 83 out of 349 samples were positive in Pharmacies, this proportion being statistically significant (χ2 = 42.9, p < 0.001). The positive samples provided evidence of at least one substance with levels greater than the limit of detection (LOD). The two most frequently detected substances were Pt (42%) and CP (30%). These accounted for 72 per cent of the whole dataset, followed by 5-FU and GEM. Based on the 90th percentile of wipe sampling data distribution, we suggest hygienic guidance values (HGVs) of 3.6, 1.0, 0.9, and 0.5 ng cm-2 for CP, 5-FU, GEM and Pt, respectively, as the best target levels of the surface contamination load in Italian pharmacies. The approach of proposing guidance values at the 90th percentile of results obtained from workplaces with good hygiene practice was found to be a simple and practical way of controlling occupational exposure. HGVs were challenged in this study as technical threshold limits to benchmark AD residual surface contamination at workplaces.

Determination of Glucocorticoids in UPLC-MS in Environmental Samples from an Occupational Setting

Occupational exposures to glucocorticoids are still a neglected issue in some work environments, including pharmaceutical plants. We developed an analytical method to quantify simultaneously 21 glucocorticoids using UPLC coupled with mass spectrometry to provide a basis to carry out environmental monitoring. Samples were taken from air, hand-washing tests, pad-tests and wipe-tests. This paper reports the contents of the analytical methodology, along with the results of this extensive environmental and personal monitoring of glucocorticoids. The method in UPLC-MS turned out to be suitable and effective for the aim of the study. Wipe-test and pad-test desorption was carried out using 50 mL syringes, a simple technique that saves time without adversely affecting analyte recovery. Results showed a widespread environmental pollution due to glucocorticoids. This is of particular concern. Evaluation of the dose absorbed by each worker and identification of a biomarker for occupational exposure will contribute to assessment and prevention of occupational exposure.

Pleural mesothelioma: Case-report of uncommon occupational asbestos exposure in a small furniture industry

The relationship between asbestos exposure and malignant mesothelioma is no longer disputed, although it is not always easy to trace past occupational exposure. This report describes a case of uncommon asbestos exposure of a small furniture industry worker, who subsequently died of pleural malignant mesothelioma, to stress the crucial importance of a full reconstruction of the occupational history, both for legal and compensation purposes. Sarcomatoid pleural mesothelioma was diagnosed in a 70-year-old man, who was previously employed as a carpenter in a small furniture industry. He worked for about 6 years in the small factory, was exposed to asbestos during the assembly of the furniture inspired by classical architecture, in which asbestos cement tubes were used to reproduce classical columns. During this production process no specific work safety measures were applied, nor masks or local aspirators. No extra-professional exposure to asbestos was identified. This mesothelioma case was investigated by the Public Prosecutors assignment that commissioned expert evidence on the legal accountability for the disease. Despite its uncommon expositive circumstance, the length of latency (about 30 years), the duration of exposure, the clinical and histochemical features are all consistent with literature evidence, accounting for the occupational origin of this malignancy.

Mortality in asbestos cement workers in Pavia, Italy: A cohort study

BACKGROUND The aim of this study was to describe the mortality of a cohort of asbestos-cement workers in the largest plant in the most industrialized Italian region (Lombardy). METHODS A cohort study was carried out on 1818 subjects, corresponding to 47 536.1 person-years of observation. Standardized mortality ratios (SMRs) were computed for the major causes of death. RESULTS Increased SMRs were observed for pleural, peritoneal and lung cancers, and for asbestosis (SMR 26.73, 95% Confidence Interval (CI) 20.99-33.55; 9.15, 95%CI 5.00-15.34; 1.48, 95%CI 1.27-1.72; and 368.05, 95%CI 214.40-589.29, respectively). No excess in mortality for laryngeal cancer was observed (SMR 0.70, 95%CI 0.30-1.39). An increased mortality for ovarian cancer (SMR 3.64, 95%CI 0.99-9.33) was observed, although it was not statistically significant. Among men, mortality for pleural malignant mesothelioma was observed to be related to the duration of exposure, though not to latency. CONCLUSIONS The results of this study are generally consistent with present knowledge. Conversely, our results do not support the hypothesis that pleural malignant mesothelioma risk indefinitely increases after exposure, suggesting instead that the alternative hypothesis of a risk plateau or decrease after a time since first exposure of more than 40 years is more consistent with the observed data.

P041 Cohorts without cohorts. mapping occupational cancer in milan great area

Introduction In Italy, we developed a monitoring system on occupational cancer, named OCCAM (Occupational Cancer Monitoring). This is a population-based case-control study that uses information already available in electronic archives, as previously described(Crosignani et al, 2006). Materials and Methods This design can be viewed as a cohort study(Pierce, 2012) when a single or a set of firms is considered. In this case we consider among cases and controls only cases and controls who worked in that/those factory/ies, as “exposed” (to that firm/s). The reference “unexposed” category is the same of the case-control design, i.e. the workers of the service and retail sector. Cases are the same of a cohort study within the time slice provided by the source(Cancer Registry or Hospital Discharge Records). Controls, “exposed” and “unexposed” carry information on the population-time that produced cases among the employees of the studied factory(ies) and among the reference cohort. This design was used to estimate cancer risks among workers. An important feature of this approach is that the enumeration of the whole cohort is not required. When employees rolls are missed or incomplete, this case-control approach is the only feasible tool for estimating cancer(and possibly other diseases) risk among the employees of a(set of) factory(ies). Using this approach we studied cancer risk among the employees of a large automotive factory in Milan great area. Cases were identified using 2000-2008 HDR and controls were concurrently sampled using Health Service population files. Results Results showed significantly increased risks for lung cancer (143 cases, RR 1.258, 95% CI: 1.052–1.505, p = 0.012) and bladder cancer (120 cases, RR 1.538, 95% CI: 1.266–1.868, p < 0.001) Conclusions Even though the job titles are unknown, these results show an increased cancer risk; in depth inquiries were carried out showing exposure to lung(asbestos, PAH, Ni, Cr) and bladder(PAH, organic dyes) carcinogens.

Occupational cancer monitoring: a unique opportunity to protect human health

Objectives Many human carcinogens were first discovered in the workplace. Even today the workers surveillance provides a unique opportunity to study and protect human health. However, a systematic exploration of cancer risk to evaluate whether workers are/were exposed to carcinogenic hazards is unusual in EU. Methods and results In Italy such a system, based on available electronic archives, is active and has proven to be very effective to: (1) estimate the cancer risk by area, economic sector and cancer site; (2) identify new or unusual economic activities where carcinogenic hazards can be present; (3) produce new hypotheses of carcinogenic hazards; (4) identify cases of potential occupational origin. Conclusions Based on our experience, and taking into account other EU experiences (eg, those of Nordic Countries), here we propose to set up a network of EU institutions and experts to assess the feasibility in each EU country of a systematic occupational cancer monitoring