Andrea Marconi

Correlation of the risk of breast cancer and disruption of the circadian rhythm (Review)

Breast cancer is the worldwide leading cause of cancer incidence among women. Night shift work exposure has been recently considered one of the significant breast cancer risk factors in industrialized countries. The mechanisms by which this work exposure may be responsible for cancer development is still discussed. In the last 15 years, many authors have paid attention to the relationship between night shift work and breast cancer risk. In the current study, eight case-control studies and four prospective epidemiological studies describing such relationship are discussed. A positive correlation between night shift work and breast cancer risk was described in 8 out of 12 studies. However, different reasons suggest that some of these studies have an Achilles heel according to the International Agency of Cancer (IARC) indications. Both the circadian system alteration and the melatonin output reduction, related to the exposure to light-at-night during night shift work, remain the most valid hypotheses on the causal relation of shift work and breast cancer. Overall, the results of the present study suggest that there is an association between night shift work and breast cancer development in western countries. However, further studies are needed to confirm such association and to understand which biomolecular mechanisms may be involved in the pathogenesis of cancer diagnosed in patients with night shift work exposure.

Fluoro‑edenite and carbon nanotubes: The health impact of 'asbestos‑like' fibres (Review)

Several decades have passed since Wagner et al demonstrated a causal link between asbestos fibre inhalation and the development of pleural mesothelioma in 1960. It was later suggested that pleural plaques are a benign consequence of exposure to these fibres. Most recently, a significant association between exposure to asbestos and cancer diagnosed at various sites, such as the peritoneum, stomach, pharynx, colon and ovaries has been demonstrated. The great concerns about public health that arose from the scientific evidence presented above have led to the banning of asbestos in several countries. Over the years, the suspicion that particles with a high aspect ratio may have asbestos-like pathogenicity has been supported by increasing evidence. Natural occurring minerals, as well as man-made fibres, have proven capable of inducing either chronic inflammation of serous membranes, or, in some cases, the development of peritoneal and pleural mesothelioma. The pathogenic role of both fluoro-edenite and carbon nanotubes, two ‘asbestos-like’ fibres is summarized and discussed in this review. The data presented herein support the notion that occupational exposure to these two types of fibre contributes to the development of different types of cancer.

FBLN-3 as a biomarker of pleural plaques in workers occupationally exposed to carcinogenic fibers: a pilot study

FBLN-3 has recently been proposed as a biomarker for malignant mesothelioma. A significantly increased standardized mortality rate from malignant mesothelioma has been reported in Biancavilla, Italy. Its cause has been identified in environmental exposure to fluoro-edenite. The aim of this study was to seek a correlation between plasma FBLN-3 concentration and pleural plaques in subjects exposed to fluoro-edenite and in a nonexposed control group. Pleural plaques was never detected in the control group, whereas it was found in 52% of exposed subjects. Median FBLN-3 concentrations were 12.96 and 5.29 ng/ml in the exposed and the control group, respectively (p < 0.001). FBLN-3 plasma levels exhibited a high predictive value for the presence of pleural plaques.

Analysis of the B-RafV600E mutation in cutaneous melanoma patients with occupational sun exposure.

Sun-exposure is one of the risk factors associated with the development of a cutaneous neoplasm. In melanoma, the Ras-Raf-MEK-ERK (MAPK) signaling pathway is constitutively activated through multiple mechanisms, including B-RAF mutation. It has been hypothesized that B-RAF mutations in melanocytic lesions arise from DNA damage induced by ultraviolet (UV) radiation. However, it is still discussed if B-RAF mutations are associated with melanoma patients exposed to the sun. Therefore, in the present study, the known B-RAFV600E mutation was analysed in melanoma samples from 30 indoor and 38 outdoor workers. B-RAFV600E mutation was detected in 52 and 73% of outdoor workers and indoor workers, respectively. Of note, this mutation was identified in 12 of 14 (85%) melanoma of the trunk diagnosed in indoor workers and in 9 of 19 (47%) samples from outdoor workers (p=0.03). By analyzing melanomas of other body sites, no statistical difference in the frequency of B-RAFV600E mutation was identified between the groups of workers. It appears that the mutation detected among indoor workers may be associated with a recreational or intermittent exposure to the sun, as usually the trunk is a sun-protected body site. Overall, these data indicate that the B-RAFV600E mutation detected in melanoma is not associated with a chronic exposure to the sun. Mutations detected in other genes may also contribute to melanoma development in the subset of patients exposed to UV radiation.

Occupational exposure to carcinogens: Benzene, pesticides and fibers (Review).

It is well known that the occupational exposure to contaminants and carcinogens leads to the development of cancer in exposed workers. In the 18th century, Percivall Pott was the first to hypothesize that chronic exposure to dust in the London chimney sweeps was associated with an increased risk of developing cancer. Subsequently a growing body of evidence indicated that other physical factors were also responsible for oncogenic mutations. Over the past decades, many carcinogens have been found in the occupational environment and their presence is often associated with an increased incidence of cancer. Occupational exposure involves several factors and the association between carcinogens, occupational exposure and cancer is still unclear. Only a fraction of factors is recognized as occupational carcinogens and for each factor, there is an increased risk of cancer development associated with a specific work activity. According to the International Agency for Research on Cancer (IARC), the majority of carcinogens are classified as ‘probable’ and ‘possible’ human carcinogens, while, direct evidence of carcinogenicity is provided in epidemiological and experimental studies. In the present review, exposures to benzene, pesticides and mineral fibers are discussed as the most important cancer risk factors during work activities.

Non‑infective occupational risk factors for hepatocellular carcinoma: A review (Review)

Liver cancer is the second leading worldwide cause of cancer-associated mortalities. Hepatocellular carcinoma, which accounts for the majority of liver tumors, ranks fifth among types of human cancer. Well-established risk factors for liver cancer include the hepatitis B and C viruses, aflatoxins, alcohol consumption, and oral contraceptives. Tobacco smoking, androgenic steroids, and diabetes mellitus are suspected risk factors. Current knowledge regarding non-infective occupational risk factors for liver cancer is inconclusive. The relevance of liver disorders to occupational medicine lies in the fact that the majority of chemicals are metabolized in the liver, and toxic metabolites generated via metabolism are the predominant cause of liver damage. However, their non-specific clinical manifestations that are similar in a number of liver diseases make diagnosis difficult. Furthermore, concomitant conditions, such as viral hepatitis and alcohol or drug abuse, may mask liver disorders that result from occupational hepatotoxic agents and block the demonstration of an occupational cause. The identification of environmental agents that result in human cancer is a long and often difficult process. The purpose of the present review is to summarize current knowledge regarding the association of non-infective occupational risk exposure and HCC, to encourage further research and draw attention to this global occupational public health problem.

Prevalence of hepatitis C virus infection among health-care workers: A 10-year survey

Hepatitis C virus (HCV) is one of the most common blood-borne pathogens transmitted from patients to health-care workers (HCWs). HCV infection status among HCWs and occupational blood exposure accidents were monitored to assess the risk of HCV infection among 403 HCWs from a single institution between 1999 and 2009. Additionally, HCV-related malignancies were evaluated in the HCV-positive HCWs. HCV infection was detected in 3% of the subjects at the first survey. The HCWs that initially tested negative for HCV remained negative during the 10 years of the survey. Of note, a statistically significant decrease was observed in the number of HCWs that experienced occupational blood exposure accidents, from 116 in 1999 to 72 in 2009 (p=0.0002). One HCV-infected HCW developed B-cell non-Hodgkin lymphoma (NHL) of the liver. The heavy chain gene combinations detected in the DNA from the NHL tissue were of the type usually found in HCV-associated lymphomas, supporting the role of HCV infection in the lymphomagenesis of this patient. The set of universal precautions recommended by the US Center for Disease Control and Prevention aided in the prevention of HCV transmission from patients to HCWs, as all 390 HCV-negative HCWs remained negative for the duration of the survey. Consequently, these recommendations also serve to prevent the development of HCV-associated malignancies such as hepatocellular carcinoma or B-cell NHL.

Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells

Exposure to asbestos is associated with the development of mesothelioma. In addition to asbestos, other fibers have been identified as risk factors for malignant and non-malignant diseases of the lungs. Among these, fluoro-edenite (FE) was found in patients from Biancavilla (Sicily, Italy) with pleural and lung disease, suggesting its role for tumor expansion. In this context, the identification of early biomarkers useful for the diagnosis of cancer is mandatory. Fibulin-3 represents an important marker for the diagnosis of mesothelioma. However, it remains to be determined whether it is directly associated with exposure to asbestos-like fibers. In the present study, peripheral blood levels of fibulin-3 from 40 asbestos-exposed workers were compared with those detected in 27 street cleaners from Biancavilla. Intriguingly, the results showed that fibulin-3 levels were higher in the group of street cleaners compared with those of the asbestos-exposed workers, suggesting that these workers used the personal protective equipment according to the current regulations. These data suggest that subjects exposed to FE should be monitored for the risk of mesothelioma. FE and volcanic particulates are probably contained within dust inhaled by street cleaners from Biancavilla during their work activities. Based on these criteria, in this study, such fibers were used to treat mesothelial cells (MeT5A) in order to verify whether fibulin-3 levels are affected by these treatments. The results showed that only treatment with FE was associated with fibulin-3 overexpression at both the transcript and protein levels. It was previously demonstrated that mesothelial cells exhibited low levels of p27 following treatment with FE. Notably, p27 downregulation is associated with stathmin upregulation in cancer, conferring an aggressive phenotype of tumor cells. This observation prompted us to perform a computational evaluation demonstrating the activation of stathmin in lung cancer in patients exposed to asbestos. Overall, it can be speculated that both fibulin-3 and stathmin overexpression may be associated with the malignant transformation of mesothelial cells following exposure to asbestos-like fibers.

A tailored health surveillance program unveils a case of MALT lymphoma in an HCV-positive health-care worker

Non-Hodgkin lymphoma (NHL) may occur among hepatitis C virus (HCV)-infected individuals. HCV is one of the most common blood-borne pathogens transmitted from patients to health-care workers (HCWs). The development of NHL among HCV-infected HCWs has recently been shown. To investigate this issue further a tailored health surveillance program was applied to 3,138 HCWs from four Medical Institutions. To this aim, all employees were screened for both anti-HCV antibodies and HCV-related extrahepatic manifestations. The HCV prevalence rate, similar among all the HCW subgroups, was 7.3%. The occurrence of a gastric mucosa-associated lymphoma tissue (MALT) lymphoma, diagnosed in a physician following a long history of HCV chronic infection, was observed. Molecular characterization of MALT tissue indicated that immunoglobuline gene combinations were those usually found among HCV-associated lymphomas. Furthermore, B-cell expansion exhibited t(14;18) translocation, as a genetic abnormality associated with the development of MALT lymphomas from HCV-positive patients. Overall, these findings support the hypothesis that HCV viral infection potentially affects the pathway of transformation and progression of lymphoma cells. The occurrence of B-cell NHL, among HCV-positive HCWs, is an additional reason to apply the standard precautions to reduce the risk of blood-borne pathogen transmission.

The risk of HCV infection among health-care workers and its association with extrahepatic manifestations (Review)

Health care workers (HCWs) are frequently exposed to different biological agents during their activities and are frequently monitored. Among these infectious agents, human hepatitis C (HCV) can infect HCWs. In this review article, the risk of HCV infection among HCWs is discussed along with extrahepatic HCV-related malignancies, such as non-Hodgkin lymphoma. Accidental contamination, represented by percutaneous and mucocutaneous infections is the main risk factor for such infection. The compliance of the protection procedures, included in the current regulation for HCWs, is the most important issue to reduce the risk of pathogen infections that in turn may produce reduction of infection-associated malignancies.