The dominant pathogenic model, somatic mutation theory (SMT), considers carcinogenesis as a ‘genetic accident’ due to the accumulation of ‘stochastic’ DNA mutations. This model was proposed and accepted by the scientific community when cancer mainly affected the elderly, but it does not explain the epidemiological observation of the continuous increase in cancer incidence among children and young adults. Somatic mutation theory has been proposed for a revision based on the emerging experimental evidence, as it does not fully address some issues that have proven to be crucial for carcinogenesis, namely: the inflammatory context of cancer; the key role played by the stroma, microenvironment, endothelial cells, activated macrophages, and surrounding tissues; and the distorted developmental course followed by the neoplastic tissue. Furthermore, SMT is often not able to consider either the existence of specific mutations resulting in a well-defined cancer type, or a clear relationship between mutations and tumor progression. Moreover, it does not explain the mechanism of action of the non-mutagenic and environmental carcinogens. In the last decade, cancer research has highlighted the prominent role of an altered regulation of gene expression, suggesting that cancer should be considered as a result of a polyclonal epigenetic disruption of stem/progenitor cells, mediated by tumour-inducing genes. The maternal and fetal exposure to a wide range of chemicals and environmental contaminants is raising the attention of the scientific community. Indeed, the most powerful procarcinogenic mechanisms of endocrine disruptors and other pollutants is linked to their potential to interfere epigenetically with the embryo-fetal programming of tissues and organs, altering the regulation of the genes involved in the cell cycle, cell proliferation, apoptosis, and other key signaling pathways. The embryo-fetal exposure to environmental, stressful, and proinflammatory triggers (first hit), seems to act as a ‘disease primer’, making fetal cells and tissues more susceptible to the subsequent environmental exposures (second hit), triggering the carcinogenic pathways. Furthermore, even at the molecular level, in carcinogenesis, ‘epigenetics precedes genetics’ as global DNA hypomethylation, and the hypermethylation of tumor suppressor genes are common both in cancerous and in precancerous cells, and generally precede mutations. These epigenetic models may better explain the increase of cancer and chronic/degenerative diseases in the last decades and could be useful to adopt appropriate primary prevention measures, essentially based on the reduction of maternal-fetal and child exposure to several procarcinogenic agents and factors dispersed in the environment and in the food-chains, as recently suggested by the World Health Organization. Full article

Epidemiological and experimental studies emphasize the link between environmental chemicals exposure and thyroid cancer. However, this association is strongly debated and the mechanisms of action of environmental thyroid carcinogens still need to be identified. The analysis of in vitro transcriptomic data developed to investigate the effects of chlorpyrifos on immortalized thyrocytes highlighted the impaired expression of genes involved in endodermal carcinogenesis. This endodermal carcinogenic gene-network (ECGN, including Zfp36l2, Dmbt1, Ddit4), was validated in cellular and mouse models of thyroid carcinogenesis, characterized by the constitutive activation of the mitogen-activated protein kinase (MAPK) pathway and in immortalized thyrocytes exposed to tetrachlorodibenzo-p-dioxin (TCDD) and chlorpyrifos (CPF). The mRNA levels of Zfp36l2, Dmbt1 and Ddit4 were increased in models characterized by MAPK activation or following TCDD exposure, whereas they were inhibited by CPF exposure. Overall, the ECGN transcripts identify a novel gene-regulatory network associated with thyroid carcinogenesis promoted by genetic mutation or by environmental carcinogens. The latter have opposite effects on the modulation of the ECGN transcripts according to their mechanisms of action in promoting carcinogenesis. Therefore, the analyses of ECGN might be helpful in discriminating compounds that promote cellular survival associated or not to proliferation of thyrocytes. Full article

Asbestos is carcinogenic to humans; the exposure to asbestos causes a wide range of diseases. Aim: Malignant mesothelioma (MM) is unique for asbestos exposure. Methods: Based on the physical inventory of asbestos-cement roofing, the social-economic situation of communes, the proximity of asbestos manufacturing plants, the land use data referring to the surface of the built-up area, and the historical data on the annexations, the amount of asbestos-containing products in use was estimated by computing best Random Forest models. Per capita asbestos use is an indicator to compare the state of asbestos use among countries. MM cases in the local administrative units (provinces) were tested by the application of Moran’s I and Getis and Ord statistic. Results: The total amount of asbestos roofing in Poland was estimated at 738,068,000 m² (8.2 million tons). In total there were 28 plants in Poland located in 11 provinces throughout the country. The amount of asbestos-cement roofing in use is correlated primarily with the measurements of asbestos concentration fibers (r_s = 0.597). MM raw morbidity rate was calculated, stratified by province, and classified into five groups with respect to incidence. Hotspots of MM cases are in the southern part of Poland. Conclusions: MM cases are concentrated in the same geographical areas, which may indicate an increasing impact of environmental exposure. The results of the local and global autocorrelation clearly indicate a statistically significant relationship between incidences of MM in provinces. Poland and other Eastern European countries are among countries with low MM incidence rate. Detailed investigation is desirable since the current MM morbidity rate in Poland seems to be underestimated. Full article

Air pollution in urban areas is a major concern as it negatively affects the health of a large number of people. The purpose of this study was to assess the inhalation health risk for exposure to PM₁₀ and benzene of the populations living in three Italian cities. Data regarding PM₁₀ and benzene daily measured by “traffic” stations and “background” stations in Torino, Perugia, and Lecce during 2014 and 2015 were compared to the limits indicated in the Directive 2008/50/EC. In addition, an inhalation risk analysis for exposure to benzene was performed for adults and children by applying the standard United States Environmental Protection Agency’s (USEPA) methodology. The levels of PM₁₀ detected in Torino exceeded the legal limits in both years with an increased mean concentration >10 µg/m³ comparing with background station. Benzene concentrations never exceeded the legislative target value. The increased cancer risk (ICR) for children exposed to benzene was greater than 1 × 10⁻⁶ only in the city of Torino, while for adults, the ICR was higher than 1 × 10⁻⁶ in all the cities. The results suggest the need for emission reduction policies to preserve human health from continuous and long exposure to air pollutants. A revision of legal limits would also be recommended. Full article

During the years 2014–2016 the University of Salento performed the “Impact of Air Quality on Health of Residents in the Municipalities of Cutrofiano, Galatina, Sogliano Cavour, Soleto and Sternatia” (IMP.AIR) study, an epidemiological-molecular research project aiming to evaluate early DNA damage in children living in an area of Salento with high incidence of lung cancer among the male population. One hundred and twenty-two children aged 6–8 years attending primary school were enrolled and the frequency of micronucleated cells (MNC) in oral mucosa was evaluated. In addition, a questionnaire was administered to parents to obtain information about personal data, anthropometric characteristics and lifestyles (physical activity, food habits, family context) of the children and perform a multivariate analysis to detect any factors associated with MNC occurrence. Data on airborne pollutants detected in the study area were acquired by the Regional Agency for the Environmental Protection. The presence of MNC was highlighted in about 42% of children with a mean MNC frequency of 0.49‰. The frequency of MNC was associated to obesity, consumption of red or processed meat and having a mother who smokes. Moreover, the prevalence of biomarkers was higher than in another area of Salento not included in the cluster area. Full article

We reviewed available evidence in medical literature concerning experimental models of exposure to ionizing radiations (IR) and their mechanisms of producing damages on living organisms. The traditional model is based on the theory of “stochastic breakage” of one or both strands of the DNA double helix. According to this model, high doses may cause the breaks, potentially lethal to the cell by damaging both DNA strands, while low doses of IR would cause essentially single strands breaks, easily repairable, resulting in no permanent damages. The available evidence makes this classical model increasingly less acceptable, because the exposure to low doses of IR seems to have carcinogenic effects, even after years or decades, both in the exposed individuals and in subsequent generations. In addition, the cells that survived the exposure to low doses, despite being apparently normal, accumulate damages that become evident in their progeny, such as nonclonal chromosomal aberrations, which can be found even in cells not directly irradiated due to the exchange of molecular signals and complex tissue reactions involving neighboring or distant cells. For all these reasons, a paradigm shift is needed, based on evidence and epigenetics. Full article

In the last decades, the incidence of thyroid cancer has increased faster than that of any other malignant tumor type. The cause of thyroid cancer is likely multifactorial and a variety of both exogenous and endogenous has been identified as potential risk factors. Polybrominated diphenyl ethers (PBDEs), used since the 1970s as flame retardants, are still widespread and persistent pollutants today, although their production was definitely phased out in the western countries several years ago. Polybrominated diphenyl ethers are known endocrine disruptors, and the endocrine system is their primary target. Whereas animal studies have ascertained the ability of PBDEs to affect the normal functionality of the thyroid, evidence in humans remains inconclusive, and only a few epidemiological studies investigated the association between exposure to PBDEs and thyroid cancer. However, a number of clues suggest that a prolonged exposure to these chemicals might act a trigger of the most common malignancy of the endocrine system, whereas further studies with an advanced design are suggested. Full article

Several epidemiological studies suggest an increased incidence of thyroid carcinoma (TC) in recent years, especially for the papillary histotype (PTC), suggesting that specific carcinogens might promote molecular abnormalities that are typical of PTC. The increased incidence is probably attributed to more intensive and sensitive diagnostic procedures, even if recent data suggest that various toxic elements could explain the phenomenon. Ionizing radiation exposure represents the most accepted risk factor for differentiated thyroid cancer that includes both the follicular and papillary histotypes. In this review, we examined the other environmental carcinogens that play a role in TC, such as eating habits, living in volcanic areas, and xenobiotic elements. Among eating habits, iodine intake represents one of the more discussed elements, because its deficiency is associated with follicular thyroid carcinomas (FTCs), while its progressive increment seems to be responsible for PTC. The gas, ash, and lava emissions of volcanoes are composed of various toxic compounds that pollute ground water, vegetables, and animals, contaminating humans via the food chain. Finally, the risk of developing PTC has also been associated with exposure of the population to xenobiotics in the environment or in the home. Their carcinogenic effects are probably caused by their accumulation, but additional studies are necessary to better understand the mechanisms of action. Full article

The area of Naples and Campania region, in Italy, are experiencing the dramatic consequences of diffuse and illegal waste dumping, resulting in possible threats to human health. This area has been referred to as the “Land of Fires” because of the common practice of waste burning. International interest in the Campania “waste emergency” has triggered several epidemiological studies. This article is aimed at highlighting the body of evidence available concerning human and environmental contamination in the Campania region, and considers the possible lack of comparable knowledge about the situation in other areas suffering from high environmental pollution. We analyzed the results of studies addressing environmental pollution and population health in the Campania region, starting from the most recent reviews on this topic, and compared their findings with those concerning other regions. We reviewed 18 studies of epidemiological/cancer surveillance and human or animal biomonitoring. These studies show worrying results, which could be considered comparable to those available for other Italian areas impacted by heavy industrial activities. The release of environmental contaminants associated with waste incineration and waste disposal in landfills poses a risk to public health, as shown by a number of studies (although not conclusively). The current knowledge available for the Campania region is better than that available for other areas which are facing similar problems due to anthropic activities, including illegal waste trafficking. Thus, Naples and Campania could represent a valuable setting to develop general models for studies of environmental and human contamination. Full article